Publications by authors named "Philip J Lupo"

208 Publications

Neighborhood Socioeconomic Deprivation and Mortality in Children with Central Nervous System Tumors.

Cancer Epidemiol Biomarkers Prev 2021 Oct 7. Epub 2021 Oct 7.

Dan L. Duncan Cancer Center, Baylor College of Medicine.

Background: While there is evidence of socioeconomic disparities in survival of children diagnosed with central nervous system (CNS) tumors, the impact of neighborhood socioeconomic deprivation on the survival of these malignancies has not been adequately studied. We investigated the association between area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, and pediatric CNS tumor survival.

Methods: Demographic and clinical characteristics, geocoded addresses at diagnosis, and vital status of pediatric CNS tumor cases (n=5,477) for the period 1995-2017 were obtained from the Texas Cancer Registry. ADI scores were computed for census tracts in Texas using the U.S. Census Bureau 2010 geography. Tracts were classified into quartiles as least, third-most, second-most, and most disadvantaged. Children were mapped to quartiles based on residency at diagnosis. The adjusted hazard ratio (HR) and 95% confidence interval (CI) were calculated.

Results: The results showed a significantly increased HR for death among children in the most (HR 1.29, 95%CI: 1.09-1.51), second-most (HR 1.18, 95%CI: 1.01-1.38) and third-most disadvantaged census tracts (HR 1.18, 95%CI: 1.02-1.37) compared to children in the least disadvantaged tracts.

Conclusion: Children living in the most disadvantaged neighborhoods experienced a significantly higher risk of mortality, indicating the important role of socioeconomic disparities in the survival of pediatric CNS tumors.

Impact: The demographic and socioeconomic disparities identified by this study should be considered when planning treatment strategies for these susceptible groups and thus, lead to a better outcome in socioeconomically disadvantaged children diagnosed with CNS tumors.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0368DOI Listing
October 2021

Comparison of the blood, bone marrow, and cerebrospinal fluid metabolomes in children with b-cell acute lymphoblastic leukemia.

Sci Rep 2021 Oct 4;11(1):19613. Epub 2021 Oct 4.

Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Metabolomics may shed light on treatment response in childhood acute lymphoblastic leukemia (ALL), however, most assessments have analyzed bone marrow or cerebrospinal fluid (CSF), which are not collected during all phases of therapy. Blood is collected frequently and with fewer risks, but it is unclear whether findings from marrow or CSF biomarker studies may translate. We profiled end-induction plasma, marrow, and CSF from N = 10 children with B-ALL using liquid chromatography-mass spectrometry. We estimated correlations between plasma and marrow/CSF metabolite abundances detected in ≥ 3 patients using Spearman rank correlation coefficients (r). Most marrow metabolites were detected in plasma (N = 661; 81%), and we observed moderate-to-strong correlations (median r 0.62, interquartile range [IQR] 0.29-0.83). We detected 328 CSF metabolites in plasma (90%); plasma-CSF correlations were weaker (median r 0.37, IQR 0.07-0.70). We observed plasma-marrow correlations for metabolites in pathways associated with end-induction residual disease (pyruvate, asparagine) and plasma-CSF correlations for a biomarker of fatigue (gamma-glutamylglutamine). There is considerable overlap between the plasma, marrow, and CSF metabolomes, and we observed strong correlations for biomarkers of clinically relevant phenotypes. Plasma may be suitable for biomarker studies in B-ALL.
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http://dx.doi.org/10.1038/s41598-021-99147-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490393PMC
October 2021

Parental perceptions of genetic testing for children with autism spectrum disorders.

Am J Med Genet A 2021 Sep 25. Epub 2021 Sep 25.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Children with autism spectrum disorder (ASD) routinely undergo genetic testing (GT) to identify the causative genetic etiology of their ASD. As there are questions about the impact of GT beyond clinical diagnosis, we conducted a mixed methods study to assess the perceived benefits of GT by exploring factors that lead parents to pursue these tests and the benefits experienced. Respondents were part of a pretest or posttest group. The pretest group (N = 22) expressed intent to pursue GT and the posttest group (N = 32) had undergone GT and received results at least 3 months prior to completing the survey. Responses were compared between and within groups. Free text responses were coded for themes and selection questions were analyzed using Fisher's exact tests. Our results demonstrate significant differences between the groups with participants in the pretest group more likely to choose "increased access to therapies" (p = 0.026) and "improved healthcare" (p < 0.000) as reasons to pursue testing. Benefits were also significantly different with "improved healthcare" (p = 0.009), "improved access to services" (p = 0.012), and "improved access to therapies" (p = 0.003) more frequently anticipated by the pretest group than reported by the posttest group. A relationship between GT and clinical management changes was reported by 34.4-50.0% of the posttest group. Among that group, genetic result type (positive, negative, or variant of uncertain significance) was associated with differing perceived benefits of testing. Thematic analysis revealed increased knowledge and coping as reported benefits in both groups. Our findings indicate a discrepancy between parental expectations and experiences of GT. Comprehensive pretest and posttest genetic counseling are necessary to improve information retention, address potential outcomes, and set expectations of GT for parents of children with ASD.
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http://dx.doi.org/10.1002/ajmg.a.62517DOI Listing
September 2021

Residence in a Hispanic Enclave Is Associated with Inferior Overall Survival among Children with Acute Lymphoblastic Leukemia.

Int J Environ Res Public Health 2021 Sep 2;18(17). Epub 2021 Sep 2.

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.

Hispanic children with acute lymphoblastic leukemia (ALL) experience poorer overall survival (OS) than non-Hispanic White children; however, few studies have investigated the social determinants of this disparity. In Texas, many Hispanic individuals reside in ethnic enclaves-areas with high concentrations of immigrants, ethnic-specific businesses, and language isolation, which are often socioeconomically deprived. We determined whether enclave residence was associated with ALL survival, overall and among Hispanic children. We computed Hispanic enclave index scores for Texas census tracts, and classified children ( = 4083) as residing in enclaves if their residential tracts scored in the highest statewide quintile. We used Cox regression to evaluate the association between enclave residence and OS. Five-year OS was 78.6% for children in enclaves, and 77.8% for Hispanic children in enclaves, both significantly lower ( < 0.05) than the 85.8% observed among children not in enclaves. Children in enclaves had increased risk of death (hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.01-1.49) after adjustment for sex, age at diagnosis, year of diagnosis, metropolitan residence and neighborhood socioeconomic deprivation and after further adjustment for child race/ethnicity (HR 1.19, 95% CI 0.97-1.45). We observed increased risk of death when analyses were restricted to Hispanic children specifically (HR 1.30, 95% CI 1.03-1.65). Observations suggest that children with ALL residing in Hispanic enclaves experience inferior OS.
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http://dx.doi.org/10.3390/ijerph18179273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430860PMC
September 2021

Detecting methylation quantitative trait loci using a methylation random field method.

Brief Bioinform 2021 Aug 19. Epub 2021 Aug 19.

Department of Epidemiology and Biostatistics, Indiana University, Bloomington, IN, USA.

DNA methylation may be regulated by genetic variants within a genomic region, referred to as methylation quantitative trait loci (mQTLs). The changes of methylation levels can further lead to alterations of gene expression, and influence the risk of various complex human diseases. Detecting mQTLs may provide insights into the underlying mechanism of how genotypic variations may influence the disease risk. In this article, we propose a methylation random field (MRF) method to detect mQTLs by testing the association between the methylation level of a CpG site and a set of genetic variants within a genomic region. The proposed MRF has two major advantages over existing approaches. First, it uses a beta distribution to characterize the bimodal and interval properties of the methylation trait at a CpG site. Second, it considers multiple common and rare genetic variants within a genomic region to identify mQTLs. Through simulations, we demonstrated that the MRF had improved power over other existing methods in detecting rare variants of relatively large effect, especially when the sample size is small. We further applied our method to a study of congenital heart defects with 83 cardiac tissue samples and identified two mQTL regions, MRPS10 and PSORS1C1, which were colocalized with expression QTL in cardiac tissue. In conclusion, the proposed MRF is a useful tool to identify novel mQTLs, especially for studies with limited sample sizes.
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http://dx.doi.org/10.1093/bib/bbab323DOI Listing
August 2021

Urban-rural residence and birth defects prevalence in Texas: a phenome-wide association study.

Pediatr Res 2021 Aug 16. Epub 2021 Aug 16.

Center for Epidemiology and Population Health, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.

Background: Some assessments indicate the prevalence of certain birth defects varies by urban-rural status. We evaluated associations between urban-rural residence and a spectrum of birth defects, using a phenome-wide association study approach in Texas, a state with large urban centers and expansive rural areas.

Methods: Data for birth defects and livebirths during 1999-2015 were obtained from the Texas Birth Defects Registry and the Center for Health Statistics. Maternal residence was classified as urban or rural, and prevalence ratios (PR) and 95% confidence intervals (CI) were calculated for any defect and 140 specific defects by Poisson regression.

Results: Overall, birth defects were less frequent in rural compared to urban counties (PR = 0.88, 95% CI: 0.87-0.89). Twelve specific defects were less prevalent in rural counties, including ventricular septal defects (VSDs; PR = 0.76, 95% CI: 0.73-0.79) and hypospadias (PR = 0.86, 95% CI: 0.82-0.89). For some birth defects, including VSDs, there was evidence of decreasing prevalence with decreasing population size.

Conclusions: In our large population-based assessment, we demonstrated that several birth defects were less prevalent in rural counties, suggesting that characteristics of urban settings may be relevant to their etiologies, diagnosis, or surveillance. Further research is needed to identify specific exposures underlying these associations.

Impact: There are few studies of birth defects prevalence in urban versus rural settings. To address this, we investigated a comprehensive range of birth defects, including several rare defects that have not been previously studied, in a large and diverse population. We identified 12 structural birth defects that were less prevalent in rural areas. Findings suggest possible differential exposures among urban and rural women, and/or possible underdiagnosis of certain birth defects in rural areas. Findings highlight the need for further study of geographically referenced risk factors for birth defects, and of the completeness of birth defects ascertainment in rural areas.
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http://dx.doi.org/10.1038/s41390-021-01700-6DOI Listing
August 2021

The frequency and efficacy of genetic testing in individuals with scimitar syndrome.

Cardiol Young 2021 Jul 2:1-8. Epub 2021 Jul 2.

Department of Pediatrics, Section of Pediatric Cardiology, Texas Children's Hospital and Baylor College of Medicine, Houston, Texas, USA.

Background: Scimitar syndrome is a rare CHD composed of partial anomalous pulmonary venous connection from the right lung, via a scimitar vein, to the inferior vena cava rather than the left atrium. Genetic conditions associated with scimitar syndrome have not been well investigated at present.

Methods: Our study included patients with scimitar syndrome diagnosed at Texas Children's Hospital from January 1987 to July 2020. Medical records were evaluated to determine if genetic testing was performed, including chromosomal microarray analysis or whole-exome sequencing. Copy number variants identified as pathogenic/likely pathogenic and variants of unknown significance were collected. Analyses of cardiac and extracardiac findings were performed via chart review.

Results: Ninety-eight patients were identified with scimitar syndrome, 89 of which met inclusion criteria. A chromosome analysis or chromosomal microarray analysis was performed in 18 patients (20%). Whole-exome sequencing was performed in six patients following negative chromosomal microarray analysis testing. A molecular genetic diagnosis was made in 7 of 18 cases (39% of those tested). Ninety-six per cent of the cohort had some type of extracardiac finding, with 43% having asthma and 20% having a gastrointestinal pathology. Of the seven patients with positive genetic testing, all had extracardiac anomalies with all but one having gastrointestinal findings and 30% having congenital diaphragmatic hernia.

Conclusions: Genetic testing revealed an underlying diagnosis in roughly 40% of those tested. Given the relatively high prevalence of pathogenic variants, we recommend chromosomal microarray analysis and whole-exome sequencing for patients with scimitar syndrome and extracardiac defects.
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http://dx.doi.org/10.1017/S1047951121002535DOI Listing
July 2021

Birth defect co-occurrence patterns in the Texas Birth Defects Registry.

Pediatr Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.

Background: The population-level landscape of co-occurring birth defects among infants without a syndromic diagnosis is not well understood.

Methods: We analyzed data from 40,771 infants with two or more major birth defects in the Texas Birth Defects Registry (TBDR; 1999-2014). We calculated adjusted observed-to-expected (O/E) ratios for all two, three, four, and five-way combinations of 138 major defects.

Results: Among 530 patterns with the highest adjusted O/E ratios (top 5% of 10,595 patterns), 66% included only defects co-occurring within one organ system and 28% were suggestive of known patterns (e.g., midline developmental defects). Of the remaining patterns, the combination of defects with the highest O/E ratio (193.8) encompassed the diaphragm, spine, spleen, and heart defects. Fourteen patterns involved heart and spine defects with or without rib defects. Ten additional patterns primarily involved two hallmark components of VACTERL association (specifically, vertebral defects, anal atresia, cardiac defects, renal, or limb defects, but not tracheoesophageal fistula).

Conclusions: Our analyses provide a description of the birth defect co-occurrence patterns in a multi-ethnic, population-based sample, and revealed several patterns of interest. This work complements prior work that has suggested etiologic connections between select defects (e.g., diaphragmatic hernia and heart and spleen anomalies; heart and spine defects).

Impact: In this large-scale, population-based study of birth defect co-occurrence patterns, we found several birth defect combinations of potential interest that warrant further investigation: congenital diaphragmatic hernia, heart, spine, and spleen defects and scimitar syndrome with vertebral defects. The majority of patterns of co-occurring defects observed more frequently than expected involved multiple defects within the same system and combinations suggestive of known associations. Nearly all of the top patterns (beyond the same system and those suggestive of known associations) involved organ systems that are components of the VACTERL association, with heart, spine, and rib defect patterns being the most common.
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http://dx.doi.org/10.1038/s41390-021-01629-wDOI Listing
June 2021

Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease.

BMC Genom Data 2021 06 10;22(1):20. Epub 2021 Jun 10.

Rady Children's Institute for Genomic Medicine, San Diego, CA, 92123, USA.

Background: Most congenital heart defects (CHDs) result from complex interactions among genetic susceptibilities, epigenetic modifications, and maternal environmental exposures. Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation will enhance our understanding of pathogenesis in this important type of congenital disorder. We investigated cis-acting effects of genetic single nucleotide polymorphisms (SNPs) on local DNA methylation patterns within 83 cardiac tissue samples and prioritized their contributions to CHD risk by leveraging results of CHD genome-wide association studies (GWAS) and their effects on cardiac gene expression.

Results: We identified 13,901 potential methylation quantitative trait loci (mQTLs) with a false discovery threshold of 5%. Further co-localization analyses and Mendelian randomization indicated that genetic variants near the HLA-DRB6 gene on chromosome 6 may contribute to CHD risk by regulating the methylation status of nearby CpG sites. Additional SNPs in genomic regions on chromosome 10 (TNKS2-AS1 gene) and chromosome 14 (LINC01629 gene) may simultaneously influence epigenetic and transcriptomic variations within cardiac tissues.

Conclusions: Our results support the hypothesis that genetic variants may influence the risk of CHDs through regulating the changes of DNA methylation and gene expression. Our results can serve as an important source of information that can be integrated with other genetic studies of heart diseases, especially CHDs.
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http://dx.doi.org/10.1186/s12863-021-00975-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194170PMC
June 2021

Using primary teeth and archived dried spots for exposomic studies in children: Exploring new paths in the environmental epidemiology of pediatric cancer.

Bioessays 2021 Sep 9;43(9):e2100030. Epub 2021 Jun 9.

Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

It is estimated that 300,000 children 0-14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high-income countries. In spite of this, the etiologies of pediatric cancer are largely unknown. Environmental exposures have long been thought to play an etiologic role. However, to date, there are few well-established environmental risk factors for pediatric malignancies, likely due to technical barriers in collecting biological samples prospectively in pediatric populations for direct measurements. In this review, we propose the use of novel or underutilized biospecimens (dried blood spots and teeth) and molecular approaches for exposure assessment (epigenetics, metabolomics, and somatic mutational profiles). Future epidemiologic studies of pediatric cancer should incorporate novel exposure assessment methodologies, data on molecular features of tumors, and a more complete assessment of gene-environment interactions.
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http://dx.doi.org/10.1002/bies.202100030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390438PMC
September 2021

Pathogenic Germline Variants in Cancer Susceptibility Genes in Children and Young Adults With Rhabdomyosarcoma.

JCO Precis Oncol 2021 11;5. Epub 2021 Jan 11.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma and accounts for 3% of all pediatric cancer. In this study, we investigated germline sequence and structural variation in a broad set of genes in two large, independent RMS cohorts.

Materials And Methods: Genome sequencing of the discovery cohort (n = 273) and exome sequencing of the secondary cohort (n = 121) were conducted on germline DNA. Analyses were performed on 130 cancer susceptibility genes (CSG). Pathogenic or likely pathogenic (P/LP) variants were predicted using the American College of Medical Genetics and Genomics (ACMG) criteria. Structural variation and survival analyses were performed on the discovery cohort.

Results: We found that 6.6%-7.7% of patients with RMS harbored P/LP variants in dominant-acting CSG. An additional approximately 1% have structural variants (, ) in CSGs. CSG variants did not influence survival, although there was a significant correlation with an earlier age of tumor onset. There was a nonsignificant excess of P/LP variants in dominant inheritance genes in the patients with fusion-negative RMS patients versus the patients with fusion-positive RMS. We identified pathogenic germline variants in CSGs previously (, , , mismatch repair genes), rarely (, , , ), or never () reported in RMS. Numerous genes (, , mismatch repair) were on the ACMG Secondary Findings 2.0 list.

Conclusion: In two cohorts of patients with RMS, we identified pathogenic germline variants for which gene-specific therapies and surveillance guidelines may be beneficial. In families with a proband with an RMS-risk P/LP variant, genetic counseling and cascade testing should be considered, especially for ACMG Secondary Findings genes and/or with gene-specific surveillance guidelines.
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http://dx.doi.org/10.1200/PO.20.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169077PMC
January 2021

Pediatric Rhabdomyosarcoma: Epidemiology and Genetic Susceptibility.

J Clin Med 2021 May 9;10(9). Epub 2021 May 9.

Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX 77030, USA.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children, yet little is known about its etiology. Studies that examine either environmental exposures or germline genetic predisposition in RMS have begun to identify factors that contribute to this malignancy. Here, we summarize epidemiological reports of RMS incidence in terms of several factors, including age at diagnosis, biological sex, and geographic location. We then describe findings from association studies, which explore the role of parental exposures, birth and perinatal characteristics, and childhood exposures in RMS. Further, we discuss RMS predisposition syndromes and large-scale sequencing studies that have further identified RMS-associated genes. Finally, we propose future directions of study, which aim to advance our understanding of the origin of RMS and can provide knowledge for novel RMS therapies.
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http://dx.doi.org/10.3390/jcm10092028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125975PMC
May 2021

A retrospective analysis of growth hormone therapy in children with Schaaf-Yang syndrome.

Clin Genet 2021 09 6;100(3):298-307. Epub 2021 Jun 6.

Institute of Human Genetics, Heidelberg University, Heidelberg, Germany.

Short stature is a common phenotype in children with Schaaf-Yang syndrome (SYS). Prader-Willi syndrome (PWS) and SYS share several phenotypic features including short stature, muscular hypotonia and developmental delay/intellectual disability. Evidence exists that similar to PWS, growth hormone (GH) deficiency may also be a feature of SYS. Recombinant human GH (rhGH) therapy has been approved for PWS, but the effects of rhGH therapy in individuals with SYS have not yet been documented. This retrospective, questionnaire-based study analyzes the prevalence of rhGH therapy in children with SYS, the effects of rhGH therapy on anthropometric measures, and parental perception of the treatment. Twenty-six individuals with SYS were sent a clinical questionnaire and a request for growth charts. We found a significant increase in height z-score (p* = 0.04) as well as a significant decrease in body mass index 6 months after rhGH therapy initiation (p* = 0.04). Furthermore, height z-scores of the treated group (mean z-score = -1.00) were significantly higher than those of the untreated group (mean z-score = -3.36, p = 0.01) at time of enrollment. All parents reported an increase in muscle strength and endurance, and several families noted beneficial effects such as improved cognition and motor development.
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http://dx.doi.org/10.1111/cge.14000DOI Listing
September 2021

Maternal and perinatal factors are associated with risk of pediatric central nervous system tumors and poorer survival after diagnosis.

Sci Rep 2021 05 17;11(1):10410. Epub 2021 May 17.

Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX, USA.

Central nervous system (CNS) tumors are the most common solid tumors in children. Findings on the role of maternal and perinatal factors on the susceptibility or outcome of these tumors are inconclusive. Therefore, we investigated the association between these early-life factors, risk, and survival of pediatric CNS tumors, using data from one of the world's largest and most diverse cancer registries. Information on pediatric CNS tumor cases (n = 1950) for the period 1995-2011 was obtained from the Texas Cancer Registry. Birth certificate controls were frequency-matched on birth year at a ratio of 10:1 for the same period. Evaluated maternal and perinatal variables were obtained from birth records. Unconditional logistic regression was used to generate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for etiological factors. Additionally, Cox proportional hazards regression was employed to assess adjusted hazard ratios (HRs) and 95% CIs for survival factors. The results indicated that Hispanic and non-Hispanic black mothers were less likely to have children with CNS tumors compared to non-Hispanic white mothers (OR 0.88 [95% CI 0.78-0.98] P-value = 0.019; OR 0.79 [95% CI 0.67-0.93 P-value = 0.004], respectively). Infants born large for gestational age (OR 1.26 [95% CI 1.07-1.47] P-value = 0.004) and those delivered pre-term (OR 1.19 [95% CI 1.04-1.38] P-value = 0.013) showed an increased risk of CNS tumors. Infants born by vaginal forceps or vacuum delivery had a higher risk of CNS tumors compared to those born by spontaneous vaginal delivery (OR 1.35 [95% CI 1.12-1.62] P-value = 0.002). Additionally, offspring of Hispanic and non-Hispanic black mothers showed a higher risk of death (HR 1.45 [95% CI 1.16-1.80] P-value = 0.001; HR 1.53 [95% CI 1.12-2.09] P-value = 0.008, respectively). Infants born by cesarean had a higher risk of death compared to those delivered vaginally (HR 1.28 [95% CI 1.05-1.57] P-value = 0.016). These findings indicate the important role of maternal and perinatal characteristics in the etiology and survival of these clinically significant malignancies.
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http://dx.doi.org/10.1038/s41598-021-88385-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129132PMC
May 2021

Synovial Sarcoma of the Hand and Foot: An Institutional Review.

Am J Clin Oncol 2021 07;44(7):361-368

Departments of Sarcoma Medical Oncology.

Objectives: Synovial sarcomas (SS) arising in distal extremities are rare and have been studied using mostly case reports and small series. We aimed to evaluate clinical presentation and survival outcomes for patients with hand or foot SS.

Materials And Methods: We conducted a retrospective review of 84 patients diagnosed with primary hand (n=20) and foot (n=64) SS between 1979 and 2019. Progression-free survival (PFS), overall survival (OS), local recurrence-free survival and metastasis-free survival were estimated using the Kaplan-Meier method and log-rank test. Cox-proportional hazards regression was used to estimate the hazard ratios.

Results: Of 84 patients, 63 (75%) presented with localized disease with 36 years median age at diagnosis (range: 4 to 76) and 21 (25%) with metastasis with 30 years median age at diagnosis (range: 15 to 64). Among patients presenting with localized disease, (1) 5 years-PFS, OS, local recurrence-free survival, and metastasis-free survival rates were 82%, 88%, 100%, and 86%, respectively. (2) Tumor size <3.0 cm corresponded to 95% 5 years-PFS (vs. 84% for 3.0 to 4.9 cm, 53% for ≥5.0 cm; P=0.007) and 100% 5 years-OS (vs. 77% for ≥3.0 cm; P=0.04). (3) Patients with ≥5.0 cm (vs. <3.0 cm) tumor size had 7.99 (95% confidence interval: 1.68, 37.91) times higher hazard of progression. Remarkably, patients presenting with metastasis had 50% 5 years-OS rate. Also, younger age (15 to 39 vs. 40 y and above) predicted better OS among patients presenting with localized disease (P=0.04) and with metastasis (P=0.03).

Conclusions: Survival outcomes are favorable for younger patients with <3.0 cm hand or foot SS. Local control is excellent, but we observed larger tumor size to be associated with poorer outcomes. Therefore, we recommend consideration of systemic therapy for patients with ≥3.0 cm hand or foot SS.
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http://dx.doi.org/10.1097/COC.0000000000000822DOI Listing
July 2021

Birth Defect Co-Occurrence Patterns Among Infants With Cleft Lip and/or Palate.

Cleft Palate Craniofac J 2021 Apr 28:10556656211010060. Epub 2021 Apr 28.

Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA.

Objective: To investigate 2- to 5-way patterns of defects co-occurring with orofacial clefts using data from a population-based registry.

Design: We used data from the Texas Birth Defects Registry for deliveries between 1999 and 2014 to Texas residents, including 1884 cases with cleft palate (CP) and 5289 cases with cleft lip with or without cleft palate (CL±P) without a known syndrome. We identified patterns of defects co-occurring with CP and with CL±P observed more frequently than would be expected if these defects occurred independently. We calculated adjusted observed-to-expected (/) ratios to account for the known tendency of birth defects to cluster nonspecifically.

Results: Among infants without a syndrome, 23% with CP and 21% with CL±P had at least 1 additional congenital anomaly. Several combinations of defects were observed much more often than expected. For example, the combination of CL±P, congenital hydrocephaly, anophthalmia, and other nose anomalies had an / ratio of 605. For both CP and CL±P, co-occurrence patterns with the highest / ratios involved craniofacial and brain abnormalities, and many included the skeletal, cardiovascular, and renal systems.

Conclusions: The patterns of defects we observed co-occurring with clefts more often than expected may help improve our understanding of the relationships between multiple defects. Further work to better understand some of the top defect combinations could reveal new phenotypic subgroups and increase our knowledge of the developmental mechanisms that underlie the respective defects.
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http://dx.doi.org/10.1177/10556656211010060DOI Listing
April 2021

Novel risk factors for glucarpidase use in pediatric acute lymphoblastic leukemia: Hispanic ethnicity, age, and the ABCC4 gene.

Pediatr Blood Cancer 2021 Aug 31;68(8):e29036. Epub 2021 Mar 31.

Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA.

Background: Carboxypeptidase G (CPDG ; glucarpidase) is a rescue drug for patients at risk for kidney injury from high-dose methotrexate (MTX). As there are no strategies for predicting patients who will require CDPG , we evaluated the role of demographic, clinical, and genetic factors for CPDG use.

Procedure: Cases who received CPDG and controls who did not were identified by chart review of acute lymphoblastic leukemia (ALL) patients who received MTX doses between 1000 and 5000 mg/m between 2010 and 2017. We used multivariable Bayesian logistic regression to evaluate the association of CPDG use with demographic and clinical variables and, on a subset of patients, with genetic ancestry and 49 single nucleotide variants previously associated with MTX toxicity.

Results: We identified 423 patients who received 1592 doses of MTX. Of the 18 patients who received CPDG , 17 (94%) were Hispanic. No patients who received 1000 or 2000 mg/m of MTX received CPDG . Hispanic ethnicity (odds ratio: 4.68; 95% compatibility interval: 1.63-15.06) and older age (1.87 [1.17-3.17]) were associated with receiving CPDG . Of the 177 patients in the genomic cohort, 11 received CPDG . Each additional G allele of rs7317112 in ABCC4 increased the odds of requiring CPDG (3.10 [1.12-6.75]). Six other loci (NTRK1/rs10908521, TSG1/rs9345389, STT3B/rs1353327, SCLO1B1/rs4149056, GATA3/rs3824662, ARID5B/rs10821936) demonstrated probabilities of association between 88% and 97%.

Conclusion: We demonstrated that demographic characteristics, including Hispanic ethnicity and age, are associated with CPDG use. Additionally, we provide evidence that inherited genetic variation is associated with risk of requiring CPDG . If validated in independent populations, this information could be leveraged to develop targeted toxicity prevention strategies for children with ALL.
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http://dx.doi.org/10.1002/pbc.29036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238882PMC
August 2021

Patterns of congenital anomalies among individuals with trisomy 13 in Texas.

Am J Med Genet A 2021 06 22;185(6):1787-1793. Epub 2021 Mar 22.

Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, Texas, USA.

Few population-based studies have analyzed patterns of co-occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co-occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999-2014. We calculated the observed-to-expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non-specifically. To address potential ascertainment differences among live births and non-live births, we repeated analyses specifically among live births. The combination of defects with the largest observed-to-expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed-to-expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition.
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http://dx.doi.org/10.1002/ajmg.a.62175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193718PMC
June 2021

Risks of nonchromosomal birth defects, small-for-gestational age birthweight, and prematurity with in vitro fertilization: effect of number of embryos transferred and plurality at conception versus at birth.

J Assist Reprod Genet 2021 Apr 5;38(4):835-846. Epub 2021 Feb 5.

Epidemiology Program, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA.

Purpose: Excess embryos transferred (ET) (> plurality at birth) and fetal heartbeats (FHB) at 6 weeks' gestation are associated with reductions in birthweight and gestation, but prior studies have been limited by small sample sizes and limited IVF data. This analysis evaluated associations between excess ET, excess FHB, and adverse perinatal outcomes, including the risk of nonchromosomal birth defects.

Methods: Live births conceived via IVF from Massachusetts, New York, North Carolina, and Texas included 138,435 children born 2004-2013 (Texas), 2004-2016 (Massachusetts and North Carolina), and 2004-2017 (New York) were classified by ET and FHB. Major birth defects were reported by statewide registries within the first year of life. Logistic regression was used to estimate adjusted odds ratios (AORs) and 95% CIs of the risks of a major nonchromosomal birth defect, small-for-gestational age birthweight (SGA), low birthweight (LBW), and preterm birth (≤36 weeks), by excess ET, and excess ET + excess FHB, by plurality at birth (singletons and twins).

Results: In singletons with [2 ET, FHB =1] and [≥3 ET, FHB=1], risks [AOR (95% CI)] were increased, respectively, for major nonchromosomal birth defects [1.13 (1.00-1.27) and 1.18 (1.00-1.38)], SGA [1.10 (1.03-1.17) and 1.15 (1.05-1.26)], LBW [1.09 (1.02-1.13) and 1.17 (1.07-1.27)], and preterm birth [1.06 (1.00-1.12) and 1.14 (1.06-1.23)]. With excess ET + excess FHB, risks of all adverse outcomes except major nonchromosomal birth defects increased further for both singletons and twins.

Conclusion: Excess embryos transferred are associated with increased risks for nonchromosomal birth defects, reduced birthweight, and prematurity in IVF-conceived births.
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http://dx.doi.org/10.1007/s10815-021-02095-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079460PMC
April 2021

The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.

Nat Commun 2021 02 5;12(1):821. Epub 2021 Feb 5.

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Down syndrome is associated with genome-wide perturbation of gene expression, which may be mediated by epigenetic changes. We perform an epigenome-wide association study on neonatal bloodspots comparing 196 newborns with Down syndrome and 439 newborns without Down syndrome, adjusting for cell-type heterogeneity, which identifies 652 epigenome-wide significant CpGs (P < 7.67 × 10) and 1,052 differentially methylated regions. Differential methylation at promoter/enhancer regions correlates with gene expression changes in Down syndrome versus non-Down syndrome fetal liver hematopoietic stem/progenitor cells (P < 0.0001). The top two differentially methylated regions overlap RUNX1 and FLI1, both important regulators of megakaryopoiesis and hematopoietic development, with significant hypermethylation at promoter regions of these two genes. Excluding Down syndrome newborns harboring preleukemic GATA1 mutations (N = 30), identified by targeted sequencing, has minimal impact on the epigenome-wide association study results. Down syndrome has profound, genome-wide effects on DNA methylation in hematopoietic cells in early life, which may contribute to the high frequency of hematological problems, including leukemia, in children with Down syndrome.
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http://dx.doi.org/10.1038/s41467-021-21064-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865055PMC
February 2021

Disparities in Cancer Survival Among Adolescents and Young Adults: A Population-Based Study of 88 000 Patients.

J Natl Cancer Inst 2021 Aug;113(8):1074-1083

Harold C. Simmons Comprehensive Cancer Center, Dallas, TX, USA.

Background: Adolescents and young adults (AYA, aged 15-39 years) diagnosed with cancer comprise a growing, yet understudied, population. Few studies have examined disparities in cancer survival in underserved and diverse populations of AYA.

Methods: Using population-based data from the Texas Cancer Registry, we estimated 5-year relative survival of common AYA cancers and examined disparities in survival by race and ethnicity, neighborhood poverty, urban or rural residence, and insurance type. We also used multivariable Cox proportional hazards regression models to examine associations of race or ethnicity, neighborhood poverty, urban or rural residence, and insurance type with all-cause mortality.

Results: We identified 55 316 women and 32 740 men diagnosed with invasive cancer at age 15-39 years between January 1, 1995, and December 31, 2016. There were disparities in relative survival by race and ethnicity, poverty, and insurance for many cancer types. Racial and ethnic disparities in survival for men with non-Hodgkin lymphoma (74.5% [95% confidence interval (CI) = 72.1% to 76.7%] White vs 57.0% [95% CI = 51.9% to 61.8%] Black) and acute lymphocytic leukemia (66.5% [95% CI = 61.4% to 71.0%] White vs 44.4% [95% CI = 39.9% to 48.8%] Hispanic) were striking, and disparities remained even for cancers with excellent prognosis, such as testicular cancer (96.6% [95% CI = 95.9% to 97.2%] White vs 88.7% [95% CI = 82.4% to 92.8%] Black). In adjusted analysis, being Black or Hispanic, living in high-poverty neighborhoods, and having Medicaid, other government insurance, or no insurance at diagnosis were associated with all-cause mortality in both women and men (all 2-sided P < .01).

Conclusions: Our study adds urgency to well-documented disparities in cancer survival in older adults by demonstrating persistent differences in relative survival and all-cause mortality in AYAs. Findings point to several areas of future research to address disparities in this unique population of cancer patients.
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http://dx.doi.org/10.1093/jnci/djab006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328976PMC
August 2021

Germline Cancer Predisposition Variants in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group.

J Natl Cancer Inst 2021 Jul;113(7):875-883

Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX, USA.

Background: Several cancer-susceptibility syndromes are reported to underlie pediatric rhabdomyosarcoma (RMS); however, to our knowledge there have been no systematic efforts to characterize the heterogeneous genetic etiologies of this often-fatal malignancy.

Methods: We performed exome-sequencing on germline DNA from 615 patients with newly diagnosed RMS consented through the Children's Oncology Group. We compared the prevalence of cancer predisposition variants in 63 autosomal-dominant cancer predisposition genes in these patients with population controls (n = 9963). All statistical tests were 2-sided.

Results: We identified germline cancer predisposition variants in 45 RMS patients (7.3%; all FOXO1 fusion negative) across 15 autosomal dominant genes, which was statistically significantly enriched compared with controls (1.4%, P = 1.3 × 10-22). Specifically, 73.3% of the predisposition variants were found in predisposition syndrome genes previously associated with pediatric RMS risk, such as Li-Fraumeni syndrome (TP53) and neurofibromatosis type I (NF1). Notably, 5 patients had well-described oncogenic missense variants in HRAS (p.G12V and p.G12S) associated with Costello syndrome. Also, genetic etiology differed with histology, as germline variants were more frequent in embryonal vs alveolar RMS patients (10.0% vs 3.0%, P = .02). Although patients with a cancer predisposition variant tended to be younger at diagnosis (P = 9.9 × 10-4), 40.0% of germline variants were identified in those older than 3 years of age, which is in contrast to current genetic testing recommendations based on early age at diagnosis.

Conclusions: These findings demonstrate that genetic risk of RMS results from germline predisposition variants associated with a wide spectrum of cancer susceptibility syndromes. Germline genetic testing for children with RMS should be informed by RMS subtypes and not be limited to only young patients.
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http://dx.doi.org/10.1093/jnci/djaa204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246828PMC
July 2021

Prevalence of structural birth defects among infants with Down syndrome, 2013-2017: A US population-based study.

Birth Defects Res 2021 01 21;113(2):189-202. Epub 2020 Dec 21.

Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas, USA.

Background: Down syndrome is the most common chromosomal disorder at birth and is often accompanied by structural birth defects. Current data on major structural defects in this population are limited.

Methods: States and territorial population-based surveillance programs submitted data on identified cases of Down syndrome and identified structural birth defects during 2013-2017. We estimated prevalence by program type and maternal and infant characteristics. Among programs with active case ascertainment, we estimated the prevalence of birth defects by organ system and for specific defects by maternal age (<35, ≥35) and infant sex.

Results: We identified 13,376 cases of Down syndrome. Prevalence among all programs was 12.7 per 10,000 live births. Among these children, 75% had at least one reported co-occurring birth defect diagnosis code. Among 6,210 cases identified by active programs, 66% had a cardiovascular defect with septal defects being the most common: atrial (32.5%), ventricular (20.6%), and atrioventricular (17.4%). Defect prevalence differed by infant sex more frequently than by maternal age. For example, atrioventricular septal defects were more common in female children (20.1% vs. 15.1%) while limb deficiencies were more prevalent in male children (0.4% vs. 0.1%).

Conclusions: Our study provides updated prevalence estimates for structural defects, including rare defects, among children with Down syndrome using one of the largest and most recent cohorts to date. These data may aid clinical care and surveillance.
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http://dx.doi.org/10.1002/bdr2.1854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978493PMC
January 2021

A Comprehensive Assessment of Co-occurring Birth Defects among Infants with Non-Syndromic Anophthalmia or Microphthalmia.

Ophthalmic Epidemiol 2021 10 20;28(5):428-435. Epub 2020 Dec 20.

Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, Texas.

Purpose: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate.

Methods: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases.

Results: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects.

Conclusion: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.
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http://dx.doi.org/10.1080/09286586.2020.1862244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214631PMC
October 2021

Operational Definitions for Chronic Liver Disease Manifestations and Recurring Clinical Events in Biliary Atresia.

J Pediatr Gastroenterol Nutr 2021 04;72(4):584-591

Division of Gastroenterology, Hepatology, and Nutrition.

Background: The disease course of biliary atresia (BA) may be complicated by development of chronic liver disease (CLD) manifestations (eg, ascites) and recurring clinical events (eg, cholangitis). Most pediatric CLD-manifestations/events lack standardized operational definitions, leading to inconsistent identification in clinical research. This study aimed to develop operational research definitions of CLD-manifestations/events in BA for application in retrospective analysis.

Methods: Operational definitions of CLD-manifestations/events were developed by literature review and revised by a panel of experienced pediatric hepatologists. Definitions were applied to a single-center review of infants with BA post-Kasai. Manifestations/events were captured until last clinical visit with native liver (SNL), liver transplantation (LT), or death. Native liver survival and event-free survival were estimated by Kaplan-Meier method. Cluster analysis was performed to identify similar patterns of manifestation/event development.

Results: Of 65 infants with BA post-Kasai (2006-18; median Kasai 56.8 days; 65% girls), 29 underwent LT (median 12.9 months) and 4 died without LT (median 6.9 months). Seventy-six percent of CLD-manifestations/events presented within the first year. Presence of definite clinically evident portal hypertension, thrombocytopenia, and dCE ascites were associated with poor transplant-free survival (P < 0.01). Similar pattern developments of CLD-manifestations/events identified 3 outcome groups: poor outcomes (87.8% LT/death), SNL with manifestations/events, and SNL with few/no events.

Conclusions: Operational definitions can provide a timely description of the disease course progression in infants with BA. Research definitions may provide better consistency in future pediatric CLD studies. Furthermore, definitions may serve as endpoints in therapeutic trials or used as variables for disease pattern identification in potential multicenter studies.
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http://dx.doi.org/10.1097/MPG.0000000000002992DOI Listing
April 2021

Patterns of co-occurring birth defects among infants with hypospadias.

J Pediatr Urol 2021 02 12;17(1):64.e1-64.e8. Epub 2020 Nov 12.

Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA. Electronic address:

Introduction: Hypospadias, one of the most common male genital birth defects, occurs in 1 out of every 200 male births in the United States and is increasing in prevalence globally.

Objective: This study aimed to characterize the combinations of birth defects that co-occur with hypospadias more often than expected by chance, while accounting for the complex clustering patterns of congenital defects.

Study Design: We analyzed cases with hypospadias and at least one additional co-occurring defect from the Texas Birth Defect Registry born between 1999 and 2014. For each combination, we calculated adjusted observed-to-expected (O/E) ratios, using Co-Occurring Defect Analysis (CODA).

Results: Among 16,442 cases with hypospadias and without known syndromes, 2,084 (12.7%) had at least one additional defect. Many of the birth defect combinations within the highest adjusted O/E ratios included cardiac, musculoskeletal, and additional urogenital defects. For example, a top combination with an adjusted O/E of 139.0 included renal agenesis and dysgenesis, reduction defects of the upper limb, and other anomalies of upper limb (including shoulder girdle). High adjusted O/E ratios were also observed in combinations that included defects outside of the urogenital developmental field. For instance, the combination with the highest O/E ratio included buphthalmos, and congenital cataract and lens anomalies (adjusted O/E ratio: 192.9). Similar results were obtained when we restricted our analyses to cases with second- or third-degree hypospadias.

Discussion: Many combinations in the top results were expected (e.g., multiple urogenital defects); however, some combinations with seemingly unrelated patterns of defects may suggest the presence of some etiologic mechanisms yet to be identified.

Conclusion: In summary, this study described patterns of co-occurring defect combinations with hypospadias that can inform further study and may provide insights for screening and diagnostic practices.
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http://dx.doi.org/10.1016/j.jpurol.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935759PMC
February 2021

Leveraging a phenome-wide approach to identify novel exposure-birth defect associations: A proof of concept using maternal smoking and a spectrum of birth defects.

Birth Defects Res 2021 03 4;113(5):439-445. Epub 2020 Dec 4.

Center for Epidemiology and Population Health, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

Background: There are often questions about the impact of exposures on a range of birth defects, but there are few rigorous approaches for evaluating these associations. Using maternal smoking as an example we applied a phenome-wide association study (PheWAS) approach to evaluate the impact of this exposure on a comprehensive range of birth defects.

Methods: Cases were obtained from the Texas Birth Defects Registry for the period 1999-2015. A total of 127 birth defects were examined. Maternal smoking at any time during the pregnancy was ascertained from the vital record. Data were randomly divided into discovery (60%) and replication (40%) partitions. Poisson regression models were run in the discovery partition, using a Bonferroni threshold of p < 3.9×10 . Birth defects passing that threshold in adjusted models were evaluated in the replication partition using p < 0.05 to determine statistical significance.

Results: Four birth defects were positively and significantly associated with maternal smoking in both partitions: cleft palate, anomalies of the pulmonary artery, other specified anomalies of the mouth and pharynx, and congenital hypertrophic pyloric stenosis. Obstructive defects of the renal pelvis and ureter showed consistent negative associations. All five defects exhibited significant dose-response relationships.

Conclusions: We demonstrated that a statistically rigorous approach can be applied to birth defects registry data to examine the association between specified exposures and a range of birth defects. While we confirmed previously reported associations, others were not validated, likely due to misclassification in exposure based on vital records.
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http://dx.doi.org/10.1002/bdr2.1851DOI Listing
March 2021

Neighborhood deprivation index is associated with weight status among long-term survivors of childhood acute lymphoblastic leukemia.

J Cancer Surviv 2021 Oct 23;15(5):767-775. Epub 2020 Nov 23.

Section of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, MS BCM622, Houston, TX, 77030, USA.

Purpose: Area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, has been linked to metabolic outcomes in the general population but has received limited attention in survivors of childhood acute lymphoblastic leukemia (ALL), a population with high rates of overweight and obesity.

Methods: We retrospectively reviewed heights and weights of ≥ 5 year survivors of pediatric ALL (diagnosed 1990-2013). Residential addresses were geocoded using ArcGIS to assign quartiles of ADI, a composite of 17 measures of poverty, housing, employment, and education, with higher quartiles reflecting greater deprivation. Odds ratios (OR) and 95% confidence intervals (CI) for the association between ADI quartiles and overweight/obesity or obesity alone were calculated with logistic regression.

Results: On average, participants (n = 454, 50.4% male, 45.2% Hispanic) were age 5.5 years at diagnosis and 17.4 years at follow-up. At follow-up, 26.4% were overweight and 24.4% obese. Compared to the lowest ADI quartile, survivors in the highest quartile were more likely to be overweight/obese at follow-up (OR = 2.33, 95% CI: 1.23-4.44) after adjusting for race/ethnicity, sex, age at diagnosis, and age at follow-up. The highest ADI quartile remained significantly associated with obesity (OR = 5.28, 95% CI: 1.79-15.54) after accounting for weight status at diagnosis.

Conclusions: This study provides novel insights into possible social determinants of health inequalities among survivors of childhood ALL by reporting a significant association between neighborhood deprivation and overweight/obesity.

Implications For Cancer Survivors: Survivors of childhood ALL residing in neighborhood with greater socioeconomic disadvantage may be at increased risk of overweight and obesity and candidates for targeted interventions.
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http://dx.doi.org/10.1007/s11764-020-00968-7DOI Listing
October 2021
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