Racial and Ethnic Disparities in Primary Cleft Lip and Cleft Palate Repair

Objective To examine the impact of race/ethnicity on timing and postoperative outcomes of primary cleft lip (CL) and cleft palate (CP) repair. Design Cross-sectional analysis of the National Surgical Quality Improvement Program Pediatric (NSQIP-P) database from 2013 to 2018. Patients and main outcome measures Patients under 2 years of age who underwent primary CL or CP repair were identified in the NSQIP-P. Outcomes were the timing of surgery and 30-day readmission and reoperation rates stratified by race and ethnicity. Results In total, 6021 children underwent CL and 6938 underwent CP repair. Adjusted rates of CL repair over time were 10% lower in Hispanic children (95%CI: 0.84–0.96) and 38% lower for Asian children (95%CI: 0.55–0.70) compared with White infants. CP repair rates over time were 13% lower in Black (95%CI: 0.79–0.95), 17% lower in Hispanic (95%CI: 0.77–0.89), and 53% lower in Asian children (95%CI: 0.43–0.53) than in White infants. Asian patients had the highest rates of delayed surgical repair, with 19.3% not meeting American Cleft Palate-Craniofacial Association (ACPA) guidelines for CL ( P < .001) and 28.2% for CP repair ( P< .001). Black and Hispanic children had 80% higher odds of readmission following primary CL repair (95%CI: 1.16–2.83 and 95%CI: 1.27–2.61, respectively). Conclusions This study of a national database identified several racial/ethnic disparities in primary CL and CP, with reduced receipt of cleft repair over time for non-White children. Asian patients were significantly more likely to have delayed cleft repair per ACPA guidelines. These findings underscore the need to better understand disparities in cleft repair timing and postoperative outcomes.

The Impact of Genetic Ancestry on the Biology and Prognosis of Childhood Acute Lymphoblastic Leukemia

INTRODUCTION Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Despite improvements in treatment over the past few decades, stark racial disparities persist in disease risk and cure rates. There is a paucity of data describing the genetic basis of these disparities, especially in relation to modern ALL molecular taxonomy and in the context of contemporary treatment regimens. To this end, we sought to determine the associations of genetic ancestry with ALL biology, and the relevance of genetic ancestry to survival outcomes of modern ALL therapy. METHODS This was a multi-national genomic study of 2,428 children with ALL on front-line trials from United States (St Jude Children's Research Hospital and Children's Oncology Group), South-East Asia (Ma-Spore trials) and Latin America (Guatemala), representing diverse populations of European (EUR), African (AFR), Native American (NA), East Asian (EAS), and South Asian (SAS) descent. We performed RNA-sequencing to characterize ALL molecular subtype, and also estimated their genetic ancestral composition by comparing allele frequencies of patient and reference genomes (1000 Genomes Project reference populations). For categorization of patients into racial groups, individuals were classified based on composition of genetic ancestry as: "white" (EUR &gt;90%), "black" (AFR &gt;70%), "Hispanic" (NA &gt;10% and NA greater than AFR), "East Asian" (EAS &gt;90%), "South Asian" (SAS &gt;70%), with the rest defined as "Other". We then evaluated the associations of ancestry with ALL molecular subtypes and survival. RESULTS Genetic ancestral composition of the entire cohort is shown in Figure 1A. Of 21 ALL subtypes, 11 showed significant associations with ancestry. Hyperdiploid ALL was most common in white children (30.6%) and the least frequent in blacks (14.4%) (P&lt;0.001). The frequency of ETV6-RUNX1 was highest in blacks (25.6%) and lowest in Hispanics (10.6%) (P&lt;0.001). The DUX4 subtype was markedly more common in Asian children (14.4% of East Asians and 14.8% of South Asians) compared to black children (1.9%) (P&lt;0.001). There was a similar trend for ZNF384 fusion, representing 6.9% of East Asians, compared to 1.7% for whites (P=0.001). TCF3-PBX1 was most prevalent in blacks at 11.9%, with the lowest at 1.7% in whites (P&lt;0.001). PAX5 alteration frequency was highest in South Asians (11.5%) and lowest in whites (4.5%) (P=0.046). CRLF2 rearrangement occurred significantly more frequently in Hispanics (9.0%) and was least common in blacks (1.3%) (P&lt;0.001). BCR-ABL1-like (excluding CRLF2) was also overrepresented in Hispanic children (11.4%), and occurred less frequently in East Asians (4.2%) (P&lt;0.001). MEF2D fusion was most common in blacks (4.4%), and rare in whites (1.4%) and South Asians (0%) (P=0.013). T-ALL differed dramatically in frequency amongst races, especially between blacks and Hispanics with a 7-fold difference (26.5% vs 3.6%, P&lt;0.001). The pattern of ALL subtype in the "Other" racial category generally mirrored that of the dominant ancestral composition, indicating a strong correlation with ancestry even within admixed populations (Figure 1B). We then examined outcomes across racial/ethnic categories. Event-free survival (EFS), overall survival (OS) and cumulative incidence of any relapse (CIR) all differed significantly across population groups (P=0.017 for EFS, P=0.05 for OS, P=0.015 for relapse). White, East Asian and South Asian children overall had more favorable outcomes compared to their black and Hispanic counterparts. Specifically, Hispanics had the poorest 5-year EFS (72.1 ± 4.2 %) and OS (82.3 ± 3.6 %), whereas South Asians had the highest EFS (94.6 ± 3.6 %) and OS (98.2 ± 2.1 %). Relapse risk trended in parallel with that of EFS and OS, with South Asians having one of the lowest CIR of 3.7 ± 2.6 %, and Hispanics having the highest at 22.8 ± 2.9 %. We repeated the analysis with genetic ancestry as a continuous variable and obtained largely similar results. Importantly, even after adjusting for biological subtypes and clinical features, Native American and African ancestries remained independently associated with poor prognosis. CONCLUSIONS ALL biology and prognosis are highly associated with genetic ancestry, pointing to a genetic basis for racial disparities in ALL. Biology-driven treatment individualization is needed to eliminate racial gaps in the cure of this cancer. Figure 1 Figure 1. Disclosures Evans: Princess Máxima Center for Pediatric Oncology, Scientific Advisory Board, Chair: Membership on an entity's Board of Directors or advisory committees; BioSkryb, Inc.: Membership on an entity's Board of Directors or advisory committees; St. Jude Children's Research Hospital, Emeritus Member (began Jan 2021): Ended employment in the past 24 months. Mullighan: Illumina: Membership on an entity's Board of Directors or advisory committees; AbbVie: Research Funding; Pfizer: Research Funding; Amgen: Current equity holder in publicly-traded company. Loh: MediSix therapeutics: Membership on an entity's Board of Directors or advisory committees. Yeoh: Amgen: Honoraria, Other: Chair, Steering Committee for ALL Academy in South East Asia. Pui: Novartis: Other: Data Monitoring Committee; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees.

Children’s cross-cultural categorizations of racially ambiguous faces in Taiwan and the U.S.

Objectives: Racially ambiguous face categorization research is growing in prominence, and yet the majority of this work has focused on White and Western samples and has primarily used biracial Black/White stimuli. Past findings suggest that biracial Black/White faces are more often seen as Black than White, but without testing these perceptions with other groups, generalizability cannot be guaranteed. Methods: We tested 3-7-year old Asian children living in Taiwan—an Eastern cultural context (N = 74)—and Asian children living in the U.S.—a Western cultural context (N = 65) to explore the role that cultural group membership may play in biracial perceptions. Children categorized 12 racially ambiguous biracial Black/White faces and 12 biracial Asian/White faces in a dichotomous forced-choice task and completed a racial constancy measurement. Results: Regarding biracial Black/White faces, Taiwanese and Asian American children both categorized the faces as White significantly more often compared to chance levels, regardless of racial constancy beliefs. For biracial Asian/White faces, Taiwanese children with racial constancy beliefs categorized the faces significantly more often as White, whereas Taiwanese children without racial constancy beliefs categorized the faces significantly more often as Asian. However, Asian American children did not show a bias in categorizing biracial Asian/White faces. Conclusions: Results suggest that hyperdescent over hypodescent for more commonly studied biracial Black/White faces generalizes in both cultural contexts. However, biracial Asian/White stimuli may be perceived in more fixed-like patterns in predominately Asian contexts, since only Taiwanese children showed increased outgroup categorizations once racial constancy beliefs were endorsed.