Development of an Outcome Measure of Observable Signs of Health and Well-Being in Infants With Orofacial Clefts.

OBJECTIVE: To develop an outcomes instrument that assesses observations that can be reliably reported by caregivers and can be used to assess health of infants with a cleft lip or cleft lip and cleft palate (CL±P) and impacts of treatments. DESIGN: Cross-sectional, mixed methods study. SETTING: Caregivers and health-care providers were recruited from 3 academic craniofacial centers and national advertisements. Most interviews were conducted by telephone, and surveys were completed online. PARTICIPANTS: Caregivers had a child less than 3 years of age with CL±P and spoke either English or Spanish. Health-care providers were members of a cleft team. Caregivers (n = 492) and health-care professionals (n = 75) participated in at least one component of this study. MAIN OUTCOME MEASURE(S): Caregivers and health-care providers participated in tasks related to instrument development: concept elicitation for items within relevant health domains, prioritization of items, and item review. RESULTS: We identified 295 observations of infant well-being across 9 health areas. Research staff and specialists evaluated items for clarity, specificity to CL±P, and responsiveness to treatment. Caregivers and health-care providers rated the resulting list of 104 observations and developed the final instrument of 65 items. CONCLUSIONS: In this phase of development of the Infant with Clefts Observation Outcomes (iCOO) instrument, items were developed to collect caregiver observations about indicators of children's health and well-being across multiple domains allowing for psychometric testing, sensitivity to changes associated with treatment, and documentation of the effects of treatment.

Practical Computed Tomography Scan Findings for Distinguishing Metopic Craniosynostosis from Metopic Ridging.

BACKGROUND: Premature fusion of the metopic suture (ie, metopic craniosynostosis) can be difficult to discriminate from physiological closure of the metopic suture with ridging (MR). Yet, MCS is treated surgically, whereas MR is treated nonsurgically. Often, the diagnosis can be made by physical examination alone, but in difficult cases, a computed tomography (CT) scan can add additional diagnostic information. METHODS: We de-identified, randomized, and analyzed the CT scans of patients with MCS (n = 52), MR (n = 20) and age-matched normative controls (n = 52) to identify specific findings helpful in distinguishing between MCS and MR. Four expert clinicians were blinded to the clinical diagnosis and assessed each CT for features of the orbits, frontal bones, and inner table of calvaria. RESULTS: Although no single feature was diagnostic of MCS, we identified several signs that were correlated with MCS, MR, or controls. Features such as "posteriorly displaced frontal bone" and "frontal bone tangent to mid-orbit or medial" demonstrated higher correlation with MCS than MR and the addition of other features improves the accuracy of diagnosis as did inclusion of the interfrontal divergence angle. CONCLUSION: The presence of a closed metopic suture in addition to other CT scan findings may improve the accuracy of diagnosing MCS, MR, and normocephaly.

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.

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.

Evaluating Trends in Headache and Revision Surgery following Cranial Vault Remodeling for Craniosynostosis.

BACKGROUND: The recommended treatment for craniosynostosis, is cranial vault expansion to prevent increased intracranial pressure and optimize developmental outcomes. Some patients complain about postoperative headaches and occasionally require revision to treat increased intracranial pressure. This study examines whether specific factors are associated with an increased risk of postoperative headaches or intracranial hypertension. METHODS: This retrospective cohort included patients with craniosynostosis from 1995 and 2010. Primary outcomes included headaches and delayed intracranial hypertension. Logistic regression was used to evaluate the associations with clinical characteristics. RESULTS: The cohort included 383 patients, of whom 127 (33 percent) complained of headaches. The positive predictive value of a headache indicating intracranial hypertension was only 9.4 percent among all patients and 6.7 percent among patients with nonsyndromic craniosynostosis. Headaches occurring in the morning, more than once per week, and associated with nausea, vomiting, or decreased activity level were most likely to be associated with delayed intracranial hypertension. Only 21 patients (6 percent) required revision surgery, and these patients were more likely to have syndromic craniosynostosis (OR, 5.6; 95 percent CI, 2.1 to 14.9), Chiari malformation (OR, 5.8; 95 percent CI, 1.7 to 19.5), or secondary craniosynostosis (additional sutures fused on the 2-year postoperative CT scan) (OR, 5.4; 95 percent CI, 2.2 to 13.5). CONCLUSIONS: Headaches are common after cranial vault remodeling but are not very predictive of who will need revision surgery for intracranial hypertension. Patients with specific headache characteristics, syndromic craniosynostosis, secondary synostosis, and Chiari malformations have the highest risk of developing delayed intracranial hypertension. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Speech and Surgical Outcomes in Children With Veau Types III and IV Cleft Palate: A Comparison of Internationally Adopted and Nonadopted Children.

OBJECTIVE: This study compares speech and surgical outcomes in internationally adopted and nonadopted patients undergoing cleft palate repair, and examines the influence of age at initial palatoplasty. DESIGN: Retrospective cohort study setting: Tertiary Care Children's Hospital. PATIENTS: 70 international adoptees and 211 nonadoptees with Veau type III and IV clefts (without associated syndrome) repaired at our institution. OUTCOME MEASURES: Outcomes included VPI, compensatory misarticulations, intelligibility, nasal air emission, oronasal fistula, and secondary speech surgery. Speech evaluations completed near 5 years of age were gathered from a prospectively collected database. RESULTS: Adoptees underwent palatoplasty 5.2 months after arrival, a mean of 10.4 months later than nonadoptees. Adoptees were significantly more likely to develop moderate/severe VPI and trended toward more frequent need for secondary speech surgery. Oronasal fistula occurred at similar rates. Increased age at initial palatoplasty was a significant predictor of moderate to severe VPI, and need for secondary speech surgery. CONCLUSIONS: International adoptees undergo palatoplasty 10.4 months later than nonadoptees and are significantly more likely to develop moderate/severe VPI, with a trend toward increased secondary speech surgery. An association between treatment delay and moderate/severe VPI and secondary speech surgery has been demonstrated. While a causal relationship between delayed repair and inferior outcomes in international adoptees has not been proven, this data suggests that surgical intervention upon unrepaired cleft palates soon after adoption may be beneficial. The opportunity for a change in practice exists, as half of the 10.4-month relative delay in palate repair occurs postadoption.

Cleft Palate Repair: Description of an Approach, Its Evolution, and Analysis of Postoperative Fistulas.

BACKGROUND: Fistulas following cleft palate repair impair speech, health, and hygiene and occur in up to 35 percent of cases. The authors detail the evolution of a surgical approach to palatoplasty; assess the rates, causes, and predictive factors of fistulas; and examine the temporal association of modifications to fistula rates. METHODS: Consecutive patients (n = 146) undergoing palatoplasty during the first 6 years of practice were included. The technique of repair was based on cleft type, and a common surgical approach was used for all repairs. RESULTS: The fistula rate was 2.4 percent (n = 125) after primary repair and 0 percent (n = 21) after secondary repair. All complications occurred in patients with type III or IV clefts. Cleft width and cleft-to-total palatal width ratio were associated with fistulas, whereas syndromes, age, and adoption were not. Most complications could also be attributed to technical factors. During the first 2 years, modifications were made around specific anatomical features, including periarticular bony hillocks, maxillopalatine suture, velopalatine pits, and tensor insertion. The fistula rate declined by one-half in subsequent years. CONCLUSIONS: The authors describe a surgical approach to cleft palate repair, its evolution, and surgically relevant anatomy. Fistulas were associated with increasing cleft severity but could also be attributed to technical factors. A reduction in frequency and severity of fistulas was consistent with a learning curve and may in part be associated with modifications to the surgical approach. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Objective Assessment of the Unilateral Cleft Lip Nasal Deformity Using Three-Dimensional Stereophotogrammetry: Severity and Outcome.

BACKGROUND: Optimization of care to correct the unilateral cleft lip nasal deformity is hampered by lack of objective measures to quantify preoperative severity and outcome. The purpose of this study was to develop a consensus standard of nasal appearance using three-dimensional stereophotogrammetry; determine whether anthropometric measurements could be used to quantify severity and outcome; and determine whether preoperative severity predicts postoperative outcome. METHODS: The authors collected facial three-dimensional images of 100 subjects in three groups: 45 infants before cleft lip repair; the same 45 infants after cleft lip repair; and 45 children aged 8 to 10 years with previous repairs. Five additional age-matched unaffected control subjects were included in each group. Seven expert surgeons ranked images in each group according to nasal appearance. The rank sum score was used as consensus standard. Anthropometric analysis was performed on each image and compared to the rank sum score. Preoperative rank and anthropometric measurements were compared to postoperative rank. RESULTS: Interrater and intrarater reliability was excellent (intraclass correlation coefficient, >0.76; Pearson correlation, >0.75) on each of the three image sets. Columellar angle, nostril width ratio, and lateral lip height ratio were highly correlated with preoperative severity and moderately correlated with postoperative nasal appearance. Postoperative outcome was associated with preoperative severity (rank and anthropometric measurement). CONCLUSIONS: Consensus ranking of preoperative severity and postoperative outcome can be achieved on three-dimensional images. Preoperative severity predicts postoperative outcomes. Columellar angle, nostril width ratio, and lateral lip height ratio are objective measures that correlate with consensus ratings by surgeons at multiple ages.

Associations between laterality of orofacial clefts and medical and academic outcomes.

Patients with oral clefts have an increased risk of other malformations, syndromes, and lower academic performance in school. Few studies have investigated if laterality of clefts is associated with medical and academic outcomes. Oral clefts have nonrandom laterality, with left-sided clefts occurring approximately twice as often as right-sided clefts. Using a retrospective study design, we examined potential associations of cleft attributes and outcomes in patients with cleft lip with or without cleft palate (CL/P) born in 2003-2010 who were treated at the Seattle Children's Craniofacial Center. The following variables were extracted from medical records: cleft type, medical history, maternal hyperglycemia, other malformations, and the need for academic support at school. We used logistic regression to examine risk of associations with outcomes of interest. Relative to patients with left-sided clefts, patients with bilateral CL/P were more likely to have a syndrome. Patients with nonsyndromic right-sided CL/P had a higher risk (OR and 95%CI: 3.5, 1.3-9.5, and 5.5, 1.9-16.0, respectively) of having other malformations and requiring academic support at school, when compared to patients with left-sided CL/P. Understanding the etiology of oral clefts is complicated, in part because both genetic and environmental factors contribute to the risk of developing a cleft. However, the different outcomes associated with cleft laterality suggest that right-sided clefts may have a distinct etiology. Using laterality to study cleft subgroups may advance our understanding of the etiology of this common birth defect.

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.