Clinical trial recruitment of people who speak languages other than english: a children's oncology group report.

BACKGROUND: Persons who speak languages other than English (LOE) are underrepresented in clinical trials; this may be due in part to inadequate multilevel resources. We conducted a survey of institutions affiliated with the Children's Oncology Group (COG) to characterize current research recruitment practices and resources regarding translation and interpretation services. METHODS: In October 2022, a 20-item survey was distributed electronically to institutions affiliated with COG to assess consent practices and resources for recruiting participants who speak LOE to COG trials. Descriptive statistics were used to summarize responses; responses were compared by institution size, type, and respondent role. RESULTS: The survey was sent to a total of 230 institutions, and the response rate was 60% (n = 139). In total, 60% (n = 83) had access to short form consents. Full consent form translation was required at 50% of institutions, and 12% of Institutional Review Boards restricted use of centrally translated consent forms. Forty-six percent of institutions reported insufficient funding to support translation costs; 15% had access to no-cost translation services. Forty-four percent (n = 61) were required to use in-person interpreters for consent discussions; the most cited barrier to obtaining consent was lack of available in-person interpreters (56%). Forty-six percent (n = 69) reported that recruiting persons who speak LOE to clinical trials was somewhat or very difficult. CONCLUSIONS: Institutions affiliated with COG face resource-specific challenges that impede recruitment of participants who speak LOE in clinical trials. These findings indicate an urgent need to identify strategies aimed at reducing recruitment barriers to ensure equitable access to clinical trials.

How trauma related to sex trafficking challenges parenting: Insights from Mexican and Central American survivors in the US.

Sex trafficking, a form of human trafficking for the purpose of commercial sexual exploitation, with a global prevalence of 4.5 million, has pervasive effects in the mental and physical health of survivors. However, little is known about the experiences and needs of Latinx migrants (the majority of sex trafficking victims in the US) after trafficking, particularly regarding parenting. This QUAL-quant study examines how 14 survivors of sex trafficking (mean age = 30) from Mexico and Central America encounter and respond to parenting experiences after escaping sexual exploitation. Combining a bio-ecological model of parenting with Zimmerman's framework on human trafficking we identified how trauma related to sex trafficking can challenge parenting and how relational and contextual pre and post trafficking factors (dis)enable women to respond to such challenges. Psychological consequences of daily victimization primarily manifested in three ways: overprotective parenting in a world perceived to be unsafe, emotional withdraw when struggling with stress and mental health symptoms, and challenges building confidence as mothers. These experiences were accentuated by pre-trafficking experiences of neglect and abuse, forced separation from their older children, poverty post-trafficking, and migration-related stressors. Yet, finding meaning in the birth of their child, having social support, and faith, also enable mothers to cope with such challenges. We conclude that motherhood after surviving sex trafficking presents new challenges and opportunities in the path to recovery from trauma. Interventions at the policy, community and individual level are needed to support survivors of sex trafficking as they enter motherhood.

Predictors of patterns of weight change 1 year after delivery in a cohort of Mexican women.

OBJECTIVE: To evaluate the associations of pregestational BMI, gestational weight gain (GWG) and breast-feeding at 1 month postpartum with four patterns of weight change during the first year after delivery: postpartum weight retention (PPWR), postpartum weight gain (PPWG), postpartum weight retention + gain (PPWR + WG) and return to pregestational weight. DESIGN: In this secondary analysis of a prospective study, we categorised postpartum weight change into four patterns using pregestational weight and weights at 1, 6 and 12 months postpartum. We evaluated their associations with pregestational BMI, GWG and breast-feeding using multinomial logistic regression. Results are presented as relative risk ratios (RRR) and 95 % CI. SETTING: Mexico City. PARTICIPANTS: Women participating in the Programming Research in Obesity, Growth, Environment and Social Stressors pregnancy cohort. RESULTS: Five hundred women were included (53 % of the cohort). Most women returned to their pregestational weight by 1 year postpartum (57 %); 8 % experienced PPWR, 14 % PPWG and 21 % PPWR + WG. Compared with normal weight, pregestational overweight (RRR 2·5, 95 % CI 1·3, 4·8) and obesity (RRR 2·2, 95 % CI 1·0, 4·7) were associated with a higher risk of PPWG. Exclusive breast-feeding, compared with no breast-feeding, was associated with a lower risk of PPWR (RRR 0·3, 95 % CI 0·1, 0·9). Excessive GWG, compared with adequate, was associated with a higher risk of PPWR (RRR 3·3, 95 % CI 1·6, 6·9) and PPWR + WG (RRR 2·4, 95 % CI 1·4, 4·2). CONCLUSIONS: Targeting women with pregestational overweight or obesity and excessive GWG, as well as promoting breast-feeding, may impact the pattern of weight change after delivery and long-term women's health.

Discovery of a transcriptomic core of genes shared in 8 primary retinoblastoma with a novel detection score analysis.

PURPOSE: Expression microarrays are powerful technology that allows large-scale analysis of RNA profiles in a tissue; these platforms include underexploited detection scores outputs. We developed an algorithm using the detection score, to generate a detection profile of shared elements in retinoblastoma as well as to determine its transcriptomic size and structure. METHODS: We analyzed eight briefly cultured primary retinoblastomas with the Human transcriptome array 2.0 (HTA2.0). Transcripts and genes detection scores were determined using the Detection Above Background algorithm (DABG). We used unsupervised and supervised computational tools to analyze detected and undetected elements; WebGestalt was used to explore functions encoded by genes in relevant clusters and performed experimental validation. RESULTS: We found a core cluster with 7,513 genes detected and shared by all samples, 4,321 genes in a cluster that was commonly absent, and 7,681 genes variably detected across the samples accounting for tumor heterogeneity. Relevant pathways identified in the core cluster relate to cell cycle, RNA transport, and DNA replication. We performed a kinome analysis of the core cluster and found 4 potential therapeutic kinase targets. Through analysis of the variably detected genes, we discovered 123 differentially expressed transcripts between bilateral and unilateral cases. CONCLUSIONS: This novel analytical approach allowed determining the retinoblastoma transcriptomic size, a shared active transcriptomic core among the samples, potential therapeutic target kinases shared by all samples, transcripts related to inter tumor heterogeneity, and to determine transcriptomic profiles without the need of control tissues. This approach is useful to analyze other cancer or tissue types.

Protective Effects of Dietary Intake of Antioxidants and Treatment-Related Toxicity in Childhood Leukemia: A Report From the DALLT Cohort.

PURPOSE: The benefits and risks of supplementation with antioxidants during cancer therapy have been a controversial area. Few studies have systematically evaluated dietary intake of antioxidants with toxicity and survival in childhood cancer. We sought to determine the role of dietary intake of antioxidants on rates of infections, mucositis, relapse, and disease-free survival during induction and postinduction phases of therapy among children and adolescents with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: We enrolled 794 children in a prospective clinical trial for treatment of ALL. Dietary intake was prospectively evaluated by a food frequency questionnaire. The association between dietary intake of antioxidants and treatment-related toxicities and survival were evaluated with the Benjamini-Hochberg false discovery rate (q) and logistic regression and the Kaplan-Meier method, respectively. RESULTS: Dietary surveys were available for analysis from 614 (77%), and 561 (71%) participants at diagnosis and at end of induction, respectively. Of 513 participants who completed the dietary surveys at both time points, 120 (23%) and 87 (16%) experienced a bacterial infection and 22 (4%) and 55 (10%) experienced mucositis during the induction or postinduction phases of treatment, respectively. Increased intake of dietary antioxidants was associated with significantly lower rates of infection and mucositis. No association with relapse or disease-free survival was observed. Supplementation was not associated with toxicity, relapse, or survival. CONCLUSION: Consumption of antioxidants through dietary intake was associated with reduced rates of infection or mucositis, with no increased risk of relapse or reduced survival. Dietary counseling on a well-balanced diet that includes an array of antioxidants from food sources alone may confer a benefit from infections and mucositis during treatment of childhood ALL.

Circulating miRNome detection analysis reveals 537 miRNAS in plasma, 625 in extracellular vesicles and a discriminant plasma signature of 19 miRNAs in children with retinoblastoma from which 14 are also detected in corresponding primary tumors.

miRNAs regulate post-transcriptional gene expression in metazoans, and thus are involved in many fundamental cellular biological processes. Extracellular miRNAs are also found in most human biofluids including plasma. These circulating miRNAs constitute a long distance inter cellular communication system and are potentially useful biomarkers. High throughput technologies like microarrays are able to scan a complete miRNome providing useful detection scores that are underexplored. We proposed to answer how many and which miRNAs are detectable in plasma or extracellular vesicles as these questions have not yet been answered. We set out to address this knowledge gap by analyzing the mirRNome in plasma and corresponding extracellular vesicles (EVs) from 12 children affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy similarly aged controls. We calculated an average of 537 detectable miRNAs in plasma and 625 in EVs. The most miRNA enriched compartment were EVs from Rb cases with an average of 656 detectable elements. Using hierarchical clustering with the detection scores, we generated broad detection mirnome maps and identified a plasma signature of 19 miRNAs present in all Rb cases that is able to discriminate cases from controls. An additional 9 miRNAs were detected in all the samples; within this group, miRNA-5787 and miRNA-6732-5p were highly abundant and displayed very low variance across all the samples, suggesting both are good candidates to serve as plasma references or normalizers. Further exploration considering participant's sex, allowed discovering 5 miRNAs which corresponded only to females and 4 miRNAs corresponding only to males. Target and pathway analysis of these miRNAs revealed hormonal function including estrogen, thyroid signaling pathways and testosterone biosynthesis. This approach allows a comprehensive unbiased survey of a circulating miRNome landscape, creating the possibility to define normality in mirnomic profiles, and to locate where in these miRNome profiles promising and potentially useful circulating miRNA signatures can be found.

Fortification of bakery and corn masa-based foods in Mexico and dietary intake of folic acid and folate in Mexican national survey data.

BACKGROUND: In Mexico, wheat and corn flour fortification with folic acid (FA) was implemented in 2001 and mandated in 2008, but without direct enforcement. Current Mexican nutrient-content tables do not account for FA contained in bakery bread and corn masa-based foods, which are dietary staples in Mexico. OBJECTIVE: The objective of this study was to examine the impact of FA fortification of dietary staples on the proportion of the population consuming below the Estimated Average Requirement (EAR) for folate or above the Tolerable Upper Intake Level (UL) for FA. METHODS: We measured FA and folate content in dietary staples (bakery bread and tortillas) using microbial assays and MS, and we recalculated FA intake from 24-h recall dietary intake data collected in the 2012 Mexican National Health and Nutrition Survey (Encuesta Nacional de Salud y Nutrición) utilizing estimates from our food measurements, using nutrient concentrations from tortillas to approximate nutrient content of other corn masa-derived foods. The revised FA intake estimates were used to examine population-level intake of FA and dietary folate equivalent (DFE) accounting for geographic differences in FA content with statistical models. RESULTS: FA content in dietary staples was variable, whereas use of FA-fortified flour in corn masa tortillas increased with population size in place of residence. Accounting for dietary staples' FA fortification increased population estimates for FA and DFE intake, resulting in a lower proportion with intake below the EAR and a higher proportion with intake above the UL. Despite accounting for FA-fortified staple foods, 9-33% of women of childbearing age still have intake below the EAR, whereas up to 12% of younger children have intake above the UL. CONCLUSIONS: Unregulated FA fortification of dietary staples leads to unpredictable total folate intake without adequately impacting the intended target. Our findings suggest that monitoring, evaluation, and enforcement of mandatory fortification policies are needed. Without these, alternate strategies may be needed in order to reach women of childbearing age while avoiding overexposing children.

Correction: Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

The original version of this Article contained an error in the undergraduate degree awarded to the author Ian Halim, which was incorrectly given as BS. This has now been corrected to BA in both the PDF and HTML versions of the Article.

Evaluation of the cost and effectiveness of diverse recruitment methods for a genetic screening study.

PURPOSE: Recruitment of participants from diverse backgrounds is crucial to the generalizability of genetic research, but has proven challenging. We retrospectively evaluated recruitment methods used for a study on return of genetic results. METHODS: The costs of study design, development, and participant enrollment were calculated, and the characteristics of the participants enrolled through the seven recruitment methods were examined. RESULTS: A total of 1118 participants provided consent, a blood sample, and questionnaire data. The estimated cost across recruitment methods ranged from $579 to $1666 per participant and required a large recruitment team. Recruitment methods using flyers and staff networks were the most cost-efficient and resulted in the highest completion rate. Targeted sampling that emphasized the importance of Latino/a participation, utilization of translated materials, and in-person recruitments contributed to enrolling a demographically diverse sample. CONCLUSIONS: Although all methods were deployed in the same hospital or neighborhood and shared the same staff, each recruitment method was different in terms of cost and characteristics of the enrolled participants, suggesting the importance of carefully choosing the recruitment methods based on the desired composition of the final study sample. This analysis provides information about the effectiveness and cost of different methods to recruit adults for genetic research.

Fluctuations in dietary intake during treatment for childhood leukemia: A report from the DALLT cohort.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Nutritional morbidities are a persistent problem facing pediatric patients during and after treatment and age-gender groups that are at risk for nutritional conditions have not been clearly identified. Therapy is a contributing factor; however, the role of dietary intake remains largely unknown. Prior to conduct of interventional trials, an understanding of the effects of treatment on fluctuations in dietary intake is necessary. METHODS: We enrolled 794 children with ALL in a prospective clinical trial. Dietary intake was collected with a food frequency questionnaire at diagnosis and throughout the course of treatment for pediatric ALL. Reported values were compared to the Dietary Recommended Intake (DRI), and normative values (NHANES). Hierarchical linear models and multilevel mixed-effects ordered logistic regression models were used to evaluate longitudinal changes in dietary intake; independent samples t-test with Bonferroni correction was performed to compare to NHANES. RESULTS: Of the evaluable participants at each timepoint, dietary intake was obtained on 81% (n = 640), 74% (n = 580) and 74% (n = 558) at diagnosis, end of induction phase of treatment, and continuation, respectively. Despite exposure to corticosteroids, caloric intake decreased over therapy for most age-gender groups. Predictive models of excess intake found reduced odds of over-consuming calories (OR 0.738, P < 0.05); however, increased odds of over-consuming fat (OR 6.971, P < 0.001). When compared to NHANES, we consistently found that ≥1/3 of children were consuming calories in excess of normative values. For select micronutrients, a small proportion of participants were above or below the DRI at each time evaluated. CONCLUSIONS: Our study suggests that dietary intake fluctuates during treatment for ALL as compared to age-gender recommended and normative values. Improving our understanding of nutrient fluctuations and dietary quality will facilitate subsequent analyses addressing relationships of dietary intake, toxicity, and survival.

Quality of Prenatal and Childhood Diet Predicts Neurodevelopmental Outcomes among Children in Mexico City.

Adequate nutrition is important for neurodevelopment. Although nutrients are ingested in combination, the impact of specific nutrients within the context of a nutrient mixture has not been studied with respect to health, such as neurodevelopment. Therefore, we examined the impact of prenatal and childhood nutrient mixtures on neurodevelopmental outcomes. Participants included mother⁻child pairs in the Programming Research in Obesity, Growth, Environment, and Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed prenatal and child micro- and macronutrient profiles among 65 and 329 children, respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4⁻6-year-old children were measured using the McCarthy Scales of Children's Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to calculate indices reflecting "good" and "poor" prenatal and childhood nutrition. After adjusting for maternal education, socioeconomic status, the Home Observation for Measurement of the Environment (HOME) score, and total caloric intake, the good prenatal and childhood nutrition indices predicted more favorable neurodevelopment, while both poor nutrition indices predicted poorer neurodevelopment. These associations were stronger in prenatal than childhood models. Monounsaturated fats predicted various neurodevelopmental abilities relatively strongly in both models. Prenatal and childhood consumption of combinations of beneficial nutrients may contribute to more favorable neurodevelopment.

miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma.

BACKGROUND: miRNAs exert their effect through a negative regulatory mechanism silencing expression upon hybridizing to their target mRNA, and have a prominent position in the control of many cellular processes including carcinogenesis. Previous miRNA studies on retinoblastoma (Rb) have been limited to specific miRNAs reported in other tumors or to medium density arrays. Here we report expression analysis of the whole miRNome on 12 retinoblastoma tumor samples using a high throughput microarray platform including 2578 mature miRNAs. METHODS: Twelve retinoblastoma tumor samples were analyzed using an Affymetrix platform including 2578 mature miRNAs. We applied RMA analysis to normalize raw data, obtained categorical data from detection call values, and also used signal intensity derived expression data. We used Diana-Tools-microT-CDS to find miRNA targets and ChromDraw to map miRNAs in chromosomes. RESULTS: We discovered a core-cluster of 30 miRNAs that were highly expressed in all the cases and a cluster of 993 miRNAs that were uniformly absent in all cases. Another 1022 miRNA were variably present in the samples reflecting heterogeneity between tumors. We explored mRNA targets, pathways and biological processes affected by some of these miRNAs. We propose that the core-cluster of 30 miRs represent miRNA machinery common to all Rb, and affecting most pathways considered hallmarks of cancer. In this core, we identified miR-3613 as a potential and critical down regulatory hub, because it is highly expressed in all the samples and its potential mRNA targets include at least 36 tumor suppressor genes, including RB1. In the variably expressed miRNA, 36 were differentially expressed between males and females. Some of the potential pathways targeted by these 36 miRNAs were associated with hormonal production. CONCLUSION: These findings indicate that Rb tumor samples share a common miRNA expression profile regardless of tumor heterogeneity, and shed light on potential novel therapeutic targets such as mir-3613 This is the first work to delineate the miRNA landscape in retinoblastoma tumor samples using an unbiased approach.

Electronic Communication Channel Use and Health Information Source Preferences Among Latinos in Northern Manhattan.

Understanding key health concepts is crucial to participation in Precision Medicine initiatives. In order to assess methods to develop and disseminate a curriculum to educate community members in Northern Manhattan about Precision Medicine, clients from a local community-based organization were interviewed during 2014-2015. Health literacy, acculturation, use of Internet, email, and text messaging, and health information sources were assessed. Associations between age and outcomes were evaluated; multivariable analysis used to examine the relationship between participant characteristics and sources of health information. Of 497 interviewed, 29.4 % had inadequate health literacy and 53.6 % had access to the Internet, 43.9 % to email, and 45.3 % to text messaging. Having adequate health literacy was associated with seeking information from a healthcare professional (OR 2.59, 95 % CI 1.54-4.35) and from the Internet (OR 3.15, 95 % CI 1.97-5.04); having ≤ grade school education (OR 2.61, 95 % CI 1.32-5.17) also preferred information from their provider; persons >45 years (OR 0.29, 95 % CI 0.18-0.47) were less likely to use the Internet for health information and preferred printed media (OR 1.64, 95 % CI 1.07-2.50). Overall, electronic communication channel use was low and varied significantly by age with those ≤45 years more likely to utilize electronic channels. Preferred sources of health information also varied by age as well as by health literacy and educational level. This study demonstrates that to effectively communicate key Precision Medicine concepts, curriculum development for Latino community members of Northern Manhattan will require attention to health literacy, language preference and acculturation and incorporate more traditional communication channels for older community members.

Socioeconomic status and global variations in the incidence of neuroblastoma: call for support of population-based cancer registries in low-middle-income countries.

Global variations in the incidence of pediatric cancers have been described; however, the causes of such differences are not known. We investigated the relationship between the incidence of embryonal tumors and human development index on a global scale. Increasing incidence of neuroblastoma correlates significantly with an increasing index of human development, with greater incidence among countries with high socioeconomic development, in apparent contrast to the incidence of retinoblastoma. While more data are needed to corroborate this observation, our findings suggest new avenues for etiological research and serve as a call for support of population-based cancer registries in low-middle-income countries.

Dietary intake and childhood leukemia: The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) cohort study.

OBJECTIVE: Children with acute lymphoblastic leukemia (ALL) are at elevated risk for nutrition-related morbidity both during and after therapy. We present the demographic characteristics and nutrient intake at study entry of a prospective cohort in which evaluating dietary intake in children diagnosed with ALL was investigated. METHODS: Dietary intake data were collected for participants enrolled on the Dana-Farber Cancer Institute ALL Consortium Protocol. Dietary intake was assessed with a food frequency questionnaire and was compared with the dietary reference intake by ALL risk group (standard and high risk). RESULTS: Dietary intake data were collected from 81% of participants (n = 640). We found that 27% of participants were overweight/obese. Intake of total calories and other nutrients exceeded the dietary reference intake in up to 79% of children. This was evident in both risk groups and was pronounced among younger children. For micronutrients, dietary intake of calcium, vitamin D (females only), and zinc differed significantly between patients with standard-risk and those with high-risk ALL. CONCLUSIONS: This study was successful in collecting dietary intake data at the time of cancer diagnosis in a multicenter setting in a pediatric population at high-risk for nutrition-related morbidity. We identified "at-risk" dietary intakes, which vary by sex and ALL risk group; such patients may benefit from future dietary interventions.

Blood lead levels in Mexico and pediatric burden of disease implications.

BACKGROUND: Although there has been success in reducing lead exposure with the phase-out of leaded gasoline, exposure to lead in Mexico continues to threaten the health of millions, much of which is from lead-based glazes used in pottery that leaches into food. OBJECTIVES: An extensive historical review and analysis of available data on blood lead levels in Mexican populations was conducted. We used a calculated geometric mean to evaluate the effect of lead on the pediatric burden of disease. METHODS: An extensive bibliographic search identified 83 published articles from 1978 to 2010 with blood lead level (BLL) data in Mexican populations representing 150 data points from more than 50,000 study participants. Values from these publications were categorized into various groupings. We then calculated the incidence of disease and disability-adjusted life-years resulting from these BLLs using the World Health Organization's burden of disease spreadsheets for mild mental retardation. RESULTS: Reviewing all relevant studies, the geometric means of Mexican BLLs in urban and rural areas were found to be 8.85 and 22.24 ug/dL, respectively. Since the phase-out of leaded gasoline, the mean in urban areas was found to be 5.36 ug/dL and the average in rural areas is expected to be much higher. The U.S. Centers for Disease Control and Prevention's (CDC) upper limit of blood lead in children under the age of 6 years is 5 ug/dL and the current U.S. average is 1.2 ug/dL. Our results indicate that more than 15% of the population will experience a decrement of more than 5 IQ points from lead exposure. The analysis also leads us to believe that lead is responsible for 820,000 disability-adjusted life-years for lead-induced mild mental retardation for children aged 0 to 4 years. CONCLUSION: Lead continues to threaten the health of millions and remains a significant cause of disability in Mexico. Additional interventions in reducing or managing lead-based ceramic glazes are necessary to protect the public health.

Neighborhood Social Context and Individual Polycyclic Aromatic Hydrocarbon Exposures Associated with Child Cognitive Test Scores.

Childhood cognitive and test-taking abilities have long-term implications for educational achievement and health, and may be influenced by household environmental exposures and neighborhood contexts. This study evaluates whether age 5 scores on the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R, administered in English) are associated with polycyclic aromatic hydrocarbon (PAH) exposure and neighborhood context variables including poverty, low educational attainment, low English language proficiency, and inadequate plumbing. The Columbia Center for Children's Environmental Health enrolled African-American and Dominican-American New York City women during pregnancy, and conducted follow-up for subsequent childhood health outcomes including cognitive test scores. Individual outcomes were linked to data characterizing 1-km network buffers around prenatal addresses, home observations, interviews, and prenatal PAH exposure data from personal air monitors. Prenatal PAH exposure above the median predicted 3.5 point lower total WPPSI-R scores and 3.9 point lower verbal scores; the association was similar in magnitude across models with adjustments for neighborhood characteristics. Neighborhood-level low English proficiency was independently associated with 2.3 point lower mean total WPPSI-R score, 1.2 point lower verbal score, and 2.7 point lower performance score per standard deviation. Low neighborhood-level educational attainment was also associated with 2.0 point lower performance scores. In models examining effect modification, neighborhood associations were similar or diminished among the high PAH exposure group, as compared with the low PAH exposure group. Early life exposure to personal PAH exposure or selected neighborhood-level social contexts may predict lower cognitive test scores. However, these results may reflect limited geographic exposure variation and limited generalizability.

Diagnostic delay and sociodemographic predictors of stage at diagnosis and mortality in unilateral and bilateral retinoblastoma.

BACKGROUND: More invasive retinoblastoma, characterized by increased morbidity and mortality, with lower rates of eye salvage and higher rates of extraocular dissemination, seems more prevalent in resource-poor countries. The relationship of diagnostic delay (lag time) and sociodemographic factors on the extent of disease at diagnosis has not been examined separately for unilateral and bilateral retinoblastoma. METHODS: At diagnosis, consenting parents of 179 Mexican children with retinoblastoma were interviewed about initial symptoms and household demographic characteristics. Clinical presentation was classified using St. Jude's, International Staging System (ISS), and International Intraocular Retinoblastoma Classification (IIRC) criteria. Lag time (delay between noting symptoms and diagnosis) and sociodemographic factors were examined as predictors for higher stage at diagnosis and overall survival (OS). RESULTS: In bilateral disease, lag time predicts stage at diagnosis using St. Jude's, and ISS criteria (P < 0.005 in multivariate regression), and OS (P < 0.05, Cox hazards), but not extent of intraocular disease (by IIRC). In unilateral disease, lag time predicts neither extent of disease (using ISS, St Jude's, and IIRC), nor OS. Indicators of prenatal poverty, including lower maternal education and the presence of dirt flooring in the home, predict more advanced disease by IIRC for bilateral retinoblastoma, and for unilateral by ISS, and St Jude's (P < 0.001) as well as OS (P < 0.05). CONCLUSION: These results suggest unilateral and bilateral retinoblastoma differs in factors governing progression and extraretinal extension, possibly reflecting underlying biologic heterogeneity. IMPACT: This demonstrates differing effect of social factors on extent of intra- and extraocular disease depending on laterality with implications for screening strategies.

Validation of a food frequency questionnaire for retrospective estimation of diet during the first 2 years of life.

This study aims to validate a Food Frequency Questionnaire (FFQ), specifically designed to retrospectively estimate dietary intake and supplement consumption during the first 2 years of life in children from resource poor households in semi-rural Mexico. The FFQ querying about diet during the first 2 years of life was administered to mothers of children (N = 84), who participated in a prospective study 3-5 years earlier, in which complementary feeding practice questionnaires and 24-h recall (24hrR) were collected at several time points during the first 2 years of life to evaluate dietary and vitamin supplement intake. The resulting FFQ data were compared to intake data collected during the original study using Spearman correlations, deattenuated correlations and Wilcoxon signed-rank tests. Total energy intake, as estimated by the retrospective and original instruments, did not differ in the second year (Yr2); correlations between the measures were significant (r = 0.40, p < 0.001). The 24hrR and FFQ-Yr2 were significantly correlated for dietary intake of vitamins B6, B12 (p < 0.001) and folate (p < 0.01); however, after including vitamin supplement intake, the two dietary instruments were correlated only for vitamins A and B12 (p < 0.05). The FFQ provides a reasonable estimate of a child's dietary intake of energy and key micronutrients during the second year of life, and permits accurate ranking of intake 3-5 years after birth.

Risk of retinoblastoma is associated with a maternal polymorphism in dihydrofolatereductase (DHFR) and prenatal folic acid intake.

BACKGROUND: The incidence of unilateral retinoblastoma varies globally, suggesting possible environmental contributors to disease incidence. Maternal intake of naturally occurring folate from vegetables during pregnancy is associated inversely with the risk of retinoblastoma in offspring. METHODS: The authors used a case-control study design to examine the association between retinoblastoma risk and maternal variations in the folate-metabolizing genes methylenetetrahydrofolate reductase (MTHFR) (a cytosine-to-thymine substitution at nucleotide 677 [MTHFR677C→T]; reference single nucleotide polymorphism rs1801133) and dihydrofolate reductase (DHFR) (a 19-base-pair deletion of intron 1a [DHFR19bpdel]; rs70991108). In central Mexico, 103 mothers of children with newly diagnosed unilateral retinoblastoma were enrolled in an institutional review board-approved study along with a control group of 97 mothers who had healthy children. Mothers were interviewed regarding perinatal characteristics, including use of prenatal vitamin supplements, and gave peripheral blood samples, which were used for polymerase chain reaction-based genotyping of rs1801133 and rs70991108. RESULTS: The risk of having a child with unilateral retinoblastoma was associated with maternal homozygosity for DHFR19bpdel (odds ratio, 3.78; 95% confidence interval, 1.89-7.55; P = .0002), even after controlling for the child's DHFR19bpdel genotype (odds ratio, 2.81; 95% confidence interval, 1.32-5.99; P = .0073). In a subgroup of 167 mothers with data on prenatal intake of supplements containing folic acid (a synthetic form of folate), DHFR19bpdel-associated risk was elevated significantly only among those who reported taking folic acid supplements. Maternal MTHFR genotype was unrelated to the risk of having a child with retinoblastoma. CONCLUSIONS: Maternal homozygosity for a polymorphism in the DHFR gene necessary for converting synthetic folic acid into biologic folate was associated with an increased risk for retinoblastoma. Prenatal ingestion of synthetic folic acid supplements may be associated with increased risk for early childhood carcinogenesis in a genetically susceptible subset of the population.