Underutilization of Lynch syndrome screening in a multisite study of patients with colorectal cancer

PurposeThe aim of this study was to examine Lynch syndrome screening of patients with metastatic colorectal cancer in integrated health-care-delivery organizations.MethodsWe determined the availability of Lynch syndrome screening criteria and actual Lynch syndrome screening in the medical records of 1,188 patients diagnosed with metastatic colorectal cancer between 2004 and 2009 at seven institutions in the Cancer Research Network.ResultsWe found infrequent use of Lynch syndrome screening (41/1,188). Family history was available for 937 of the 1,188 patients (79%). There was sufficient information to assess Lynch syndrome risk using family history–based criteria in 719 of the 937 patients (77%) with family history documentation. In 391 individuals with a family history of a Lynch syndrome–associated cancer, 107 (27%) could not be evaluated due to missing information such as age of cancer onset. Eleven percent of patients who met the Bethesda criteria and 25% of individuals who met the Amsterdam II criteria were screened for Lynch syndrome. Recommended guidelines were adhered to during screening, but no testing method was preferred.ConclusionThe information required for Lynch syndrome screening decisions is routinely collected but seldom used. There is a critical gap between collection of family history and its use to guide Lynch syndrome screening, which may support a case for implementation of universal screening guidelines.Genet Med15 12, 933–940.     

Clinical predictors of genetic testing outcomes in hypertrophic cardiomyopathy

PurposeGenetic testing for hypertrophic cardiomyopathy has been commercially available for almost a decade; however, low mutation detection rate and cost have hindered uptake. This study sought to identify clinical variables that can predict probands with hypertrophic cardiomyopathy in whom a pathogenic mutation will be identified.MethodsProbands attending specialized cardiac genetic clinics across Australia over a 10-year period (2002–2011), who met clinical diagnostic criteria for hypertrophic cardiomyopathy and who underwent genetic testing for hypertrophic cardiomyopathy were included. Clinical, family history, and genotype information were collected.ResultsA total of 265 unrelated individuals with hypertrophic cardiomyopathy were included, with 138 (52%) having at least one mutation identified. The mutation detection rate was significantly higher in the probands with hypertrophic cardiomyopathy with an established family history of disease (72 vs. 29%, P < 0.0001), and a positive family history of sudden cardiac death further increased the detection rate (89 vs. 59%, P < 0.0001). Multivariate analysis identified female gender, increased left-ventricular wall thickness, family history of hypertrophic cardiomyopathy, and family history of sudden cardiac death as being associated with greatest chance of identifying a gene mutation. Multiple mutation carriers (n = 16, 6%) were more likely to have suffered an out-of-hospital cardiac arrest or sudden cardiac death (31 vs. 7%, P = 0.012).ConclusionFamily history is a key clinical predictor of a positive genetic diagnosis and has direct clinical relevance, particularly in the pretest genetic counseling setting.Genet Med15 12, 972–977.     

Preliminary validation of a consumer-oriented colorectal cancer risk assessment tool compatible with the US Surgeon General’s My Family Health Portrait

PurposeThis study examines the analytic validity of a software tool designed to provide individuals with risk assessments for colorectal cancer based on personal health and family history information. The software is compatible with the US Surgeon General’s My Family Health Portrait (MFHP).MethodsAn algorithm for risk assessment was created using accepted colorectal risk assessment guidelines and programmed into a software tool (MFHP). Risk assessments derived from 150 pedigrees using the MFHP tool were compared with “gold standard” risk assessments developed by three expert cancer genetic counselors.ResultsGenetic counselor risk assessments showed substantial, but not perfect, agreement. MFHP risk assessments for colorectal cancer yielded a sensitivity for colorectal cancer risk of 81% (95% confidence interval: 54–96%) and specificity of 90% (95% confidence interval: 83–94%), as compared with genetic counselor pedigree review. The positive predictive value for risk for MFHP was 48% (95% confidence interval: 29–68%), whereas the negative predictive value was 98% (95% confidence interval: 93–99%). Agreement between MFHP and genetic counselor pedigree review was moderate (κ = 0.54).ConclusionThe analytic validity of the MFHP colorectal cancer risk assessment software is similar to those of other types of screening tools used in primary care. Future investigations should explore the clinical validity and utility of the software in diverse population groups.Genet Med17 9, 753–756.     

BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer: a PACGENE study

PurposeFamilial pancreatic cancer kindreds contain at least two affected first-degree relatives. Comprehensive data are needed to assist clinical risk assessment and genetic testing.MethodsGerm-line DNA samples from 727 unrelated probands with positive family history (521 met criteria for familial pancreatic cancer) were tested in compliance with the Clinical Laboratory Improvement Amendments for mutations in BRCA1 and BRCA2 (including analysis of deletions and rearrangements), PALB2, and CDKN2A. We compared prevalence of deleterious mutations between familial pancreatic cancer probands and nonfamilial pancreatic cancer probands (kindreds containing at least two affected biological relatives, but not first-degree relatives). We also examined the impact of family history on breast and ovarian cancers and melanoma.ResultsPrevalence of deleterious mutations (excluding variants of unknown significance) among familial pancreatic cancer probands was: BRCA1, 1.2%; BRCA2, 3.7%; PALB2, 0.6%; and CDKN2A, 2.5%. Four novel deleterious mutations were detected. Familial pancreatic cancer probands carry more mutations in the four genes (8.0%) than nonfamilial pancreatic cancer probands (3.5%) (odds ratio: 2.40; 95% confidence interval: 1.06−5.44; P = 0.03). The probability of testing positive for deleterious mutations in any of the four genes ranges up to 10.4%, depending on family history of cancers. BRCA2 and CDKN2A account for the majority of mutations in familial pancreatic cancer.ConclusionGenetic testing of multiple relevant genes in probands with a positive family history is warranted, particularly for familial pancreatic cancer.Genet Med 17 7, 569–577.     

Family history and the natural history of colorectal cancer: systematic review

PurposeFamily history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks.MethodsWe conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening.ResultsWe found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than the commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family-history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC but no evidence for differential adenoma location or adenoma progression by family history. Limited data regarding the natural history of CRC by family history suggest a differential age or stage at cancer diagnosis and mixed evidence with respect to tumor location. Adherence to recommended colonoscopy screening was higher in people with a family history of CRC.ConclusionStratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history–based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.Genet Med17 9, 702–712.     

Patient interest in recording family histories of cancer via the Internet

PurposeThis study investigated the interest of mammogram patients in using electronic tools for recording their family histories of cancer (FHC).MethodsSemistructured interviews were conducted with 65 patients visiting a breast center at a referral hospital in Cleveland, Ohio.ResultsMost (n = 40; 62%) respondents expressed interest in using an electronic tool for recording FHC and associated its use with a range of benefits to themselves, their families, and their health care providers. Women who were not interested (n = 25; 38%) in using an electronic tool for recording FHC were concerned about privacy issues, computer proficiency, and giving up the opportunity to provide family history information directly to the health care provider. Interest in using an electronic tool for recording FHC was not significantly associated with age, race, level of education or income, personal or FHC, or Internet access and frequency of use.ConclusionElectronic documentation of FHC was seen as largely desirable. However, clinical services to facilitate systematic family history documentation are likely to require more than one avenue for collecting and communicating this information, as not everyone who wants to provide a FHC to a health care provider is comfortable using the Internet to do so.     

Educational needs about cancer family history and genetic counseling for cancer risk among frontline healthcare clinicians in New York City

PurposeThis study investigated the educational needs of frontline healthcare clinicians about cancer family history and genetic counseling for cancer risk.MethodsWe conducted a voluntary, anonymous survey among (1) general medicine clinicians, (2) obstetrics/gynecology clinicians, and (3) nurse practitioners at Mount Sinai School of Medicine in New York City.ResultsA total of 143 clinicians completed the survey (response rate 81%). The majority of clinicians (77.5%) reported regularly completing family histories on cancer risk for their patients, but only 1.7% considered themselves “experts” in interpreting risk to make prevention, screening, and treatment recommendations. Numerous barriers to cancer family history collection were noted. More than half (55.8%) reported referring patients to genetic counseling, although only 14.3% reported confidence in their ability to make appropriate referrals. The majority reported that they would apply genetic counseling for cancer risk in their practice if they had the skills (84.9%). There was some variability found regarding specialty.ConclusionDespite widespread use of family histories for cancer risk, barriers remain to appropriate cancer risk management among frontline healthcare clinicians. Development of educational training programs to assist clinicians with collection of cancer family history information, interpretation, and appropriate referral along with teaching direct application of a modified form of genetic counseling for low-medium risk patients and referral of patients at genetic risk is warranted.     

Factors influencing organizational adoption and implementation of clinical genetic services

PurposeWe sought to identify characteristics of genetic services that facilitate or hinder adoption.MethodsWe conducted semi-structured key informant interviews in five clinical specialties (primary care, medical oncology, neurology, cardiology, pathology/laboratory medicine) within 13 Veterans Administration facilities.ResultsGenetic services (defined as genetic testing and consultation) were not typically characterized by informants (n = 64) as advantageous for their facilities or their patients; compatible with organizational norms of low cost and high clinical impact; or applicable to patient populations or norms of clinical care. Furthermore, genetic services had not been systematically adopted in most facilities because of their complexity: knowledge of and expertise on genetic testing was limited, and organizational barriers to utilization of genetic services were formidable. The few facilities that had some success with implementation of genetic services had knowledgeable clinicians interested in developing services and organizational-level facilitators such as accessible genetic test–ordering processes.ConclusionAdoption and implementation of genetic services will require a multilevel effort that includes education of providers and administrators, opportunities for observing the benefits of genetic medicine, strategies for reducing the complexity of genomic medicine, expanded strategies for accessing genetics expertise and streamlining utilization, and resources dedicated to assessing the value of genetic information for the outcomes that matter to health-care organizations.Genet Med 2014:16(3):238–245.     

Genetic testing impacts the utility of prospective familial screening in hypertrophic cardiomyopathy through identification of a nonfamilial subgroup

PurposeHypertrophic cardiomyopathy (HCM) is considered a hereditary autosomal dominant condition, but genetic testing is positive in only half of patients. In patients with negative genetic tests, the inheritance pattern and utility of family screening are unclear.MethodsSubjects with HCM were prospectively enrolled in a registry. A survey at a median follow-up of 4 years determined the yield of family screening.ResultsThe outcome of cardiac screening on 267 family members was reported by 120 survey respondents. Subjects with positive genetic test or family history (n=74, 62%) reported an HCM diagnosis in 34 of 203 first-degree relatives who were screened (17%). Affected family members were diagnosed at a mean age of 30–39 years, and 22 of 34 experienced HCM-related adverse events (65%). Gene test–negative subjects with no prior family history of HCM (n=46, 38%) reported an HCM diagnosis in only 2 of 64 first-degree relatives who were screened (3%, p<0.001). These two individuals were diagnosed at age >40 years without HCM-related adverse events.ConclusionHypertrophic cardiomyopathy is a heterogeneous disorder, only half of which tracks with a Mendelian inheritance pattern. Negative genetic testing and family history indicates a more complex genetic basis corresponding to low risk for family members.     

Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial

PurposeIncreasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed.MethodsIn this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH−) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months.ResultsA total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of −10; mean difference = 2.45; 95% confidence interval −2.87–7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001).ConclusionA streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448–456.     

Electronic health record interventions at the point of care improve documentation of care processes and decrease orders for genetic tests commonly ordered by nongeneticists

ObjectiveTo determine whether electronic health record (EHR) tools improve documentation of pre- and postanalytic care processes for genetic tests ordered by nongeneticists.MethodsWe conducted a nonrandomized, controlled, pre-/postintervention study of EHR point-of-care tools (informational messages and template report) for three genetic tests. Chart review assessed documentation of genetic testing processes of care, with points assigned for each documented item. Multiple linear and logistic regressions assessed factors associated with documentation.ResultsPreimplementation, there were no significant site differences (P > 0.05). Postimplementation, mean documentation scores increased (5.9 (2.1) vs. 5.0 (2.2); P = 0.0001) and records with clinically meaningful documentation increased (score >5: 59 vs. 47%; P = 0.02) at the intervention versus the control site. Pre- and postimplementation, a score >5 was positively associated with abnormal test results (OR = 4.0; 95% CI: 1.8–9.2) and trainee provider (OR = 2.3; 95% CI: 1.2–4.6). Postimplementation, a score >5 was also positively associated with intervention site (OR = 2.3; 95% CI: 1.1–5.1) and specialty clinic (OR = 2.0; 95% CI: 1.1–3.6). There were also significantly fewer tests ordered after implementation (264/100,000 vs. 204/100,000; P = 0.03), with no significant change at the control site (280/100,000 vs. 257/100,000; P = 0.50).ConclusionsEHR point-of-care tools improved documentation of genetic testing processes and decreased utilization of genetic tests commonly ordered by nongeneticists.     

Genetic testing and cancer risk management recommendations by physicians for at-risk relatives

PurposeSequence-based cancer susceptibility testing results are described as negative, deleterious mutation or variant of uncertain significance. We studied the impact of different types of test results on clinical decision making.MethodsPracticing physicians from five specialties in Texas completed an online case-based survey (n = 225). Respondents were asked to make genetic testing and management recommendations for healthy at-risk relatives of patients with cancer.ResultsWhen the patient carried a deleterious BRCA1 mutation or variant of uncertain significance, 98% and 82% of physicians, respectively, recommended testing of at-risk relatives (P < 0.0001). In both situations, comprehensive BRCA1/2 analysis was selected most with a corresponding 9-fold increase in unnecessary genetic testing costs. There was no difference in physicians with (n = 81) or without (n = 144) prior BRCA1/2 testing experience (P = 0.3869). Cancer risk management recommendations were most intense for the relative with a deleterious mutation compared with variant of uncertain significance, negative, or no testing with 63%, 13%, 5%, and 2%, respectively, recommending oophorectomy (P < 0.0001).ConclusionIndependent of experience, or specialty, physicians chose more comprehensive testing for healthy relatives than current guidelines recommend. In contrast, management decisions demonstrated the uncertainty associated with a variant of uncertain significance. Utilization of genetic professionals and education of physicians on family-centered genetic testing may improve efficacy and substantially reduce costs. Genet Med 2011:13(2):148–154.     

Diagnosing hereditary cancer predisposition in men with prostate cancer

PurposeWe describe the pathogenic variant spectrum and identify predictors of positive results among men referred for clinical genetic testing for prostate cancer.MethodsOne thousand eight hundred twelve men with prostate cancer underwent clinical multigene panel testing between April 2012 and September 2017. Stepwise logistic regression determined the most reliable predictors of positive results among clinical variables reported on test requisition forms.ResultsA yield of 9.4–12.1% was observed among men with no prior genetic testing. In this group, the positive rate of BRCA1 and BRCA2 was 4.6%; the positive rate for the mismatch repair genes was 2.8%. Increasing Gleason score (odds ratio [OR] 1.19; 95% confidence interval [CI] 0.97–1.45); personal history of breast or pancreatic cancer (OR 3.62; 95% CI 1.37–9.46); family history of breast, ovarian, or pancreatic cancer (OR 2.32 95% CI 1.48–3.65); and family history of Lynch syndrome–associated cancers (OR 1.97; 95% CI 1.23–3.15) were predictors of positive results.ConclusionThese results support multigene panel testing as the primary genetic testing approach for hereditary prostate cancer and are supportive of recommendations for consideration of germline testing in men with prostate cancer. Expanding the criteria for genetic testing should be considered as many pathogenic variants are actionable for treatment of advanced prostate cancer.     

Adopting genetics: motivations and outcomes of personal genomic testing in adult adoptees

PurposeAmerican adult adoptees may possess limited information about their biological families and turn to direct-to-consumer personal genomic testing (PGT) for genealogical and medical information. We investigated the motivations and outcomes of adoptees undergoing PGT using data from the Impact of Personal Genomics (PGen) Study.MethodsThe PGen Study surveyed new 23andMe and Pathway Genomics customers before and 6 months after receiving PGT results. Exploratory analyses compared adoptees’ and nonadoptees’ PGT attitudes, expectations, and experiences. We evaluated the association of adoption status with motivations for testing and postdisclosure actions using logistic regression models.ResultsOf 1,607 participants, 80 (5%) were adopted. As compared with nonadoptees, adoptees were more likely to cite limited knowledge of family health history (OR = 10.1; 95% CI = 5.7–19.5) and the opportunity to learn genetic disease risks (OR = 2.7; 95% CI = 1.6–4.8) as strong motivations for PGT. Of 922 participants who completed 6-month follow-up, there was no significant association between adoption status and PGT-motivated health-care utilization or health-behavior change.ConclusionPGT allows adoptees to gain otherwise inaccessible information about their genetic disease risks and ancestry, helping them to fill the void of an incomplete family health history.Genet Med 18 9, 924–932.     

Effectiveness of oncogenetics training on general practitioners’ consultation skills: a randomized controlled trial

PurposeGeneral practitioners are increasingly called upon to deliver genetic services and could play a key role in translating potentially life-saving advancements in oncogenetic technologies to patient care. If general practitioners are to make an effective contribution in this area, their genetics competencies need to be upgraded. The aim of this study was to investigate whether oncogenetics training for general practitioners improves their genetic consultation skills.MethodsIn this pragmatic, blinded, randomized controlled trial, the intervention consisted of a 4-h training (December 2011 and April 2012), covering oncogenetic consultation skills (family history, familial risk assessment, and efficient referral), attitude (medical ethical issues), and clinical knowledge required in primary-care consultations. Outcomes were measured using observation checklists by unannounced standardized patients and self-reported questionnaires.ResultsOf 88 randomized general practitioners who initially agreed to participate, 56 completed all measurements. Key consultation skills significantly and substantially improved; regression coefficients after intervention were equivalent to 0.34 and 0.28 at 3-month follow-up, indicating a moderate effect size. Satisfaction and perceived applicability of newly learned skills were highly scored.ConclusionThe general practitioner–specific training proved to be a feasible, satisfactory, and clinically applicable method to improve oncogenetics consultation skills and could be used as an educational framework to inform future training activities with the ultimate aim of improving medical care.Genet Med16 1, 45–52.     

Underutilization of BRCA1/2 testing to guide breast cancer treatment: Black and Hispanic women particularly at risk

PurposeWomen with early-onset (age ≤40 years) breast cancer are at high risk of carrying deleterious mutations in the BRCA1/2 genes; genetic assessment is thus recommended. Knowledge of BRCA1/2 mutation status is useful in guiding treatment decisions. To date, there has been no national study of BRCA1/2 testing among newly diagnosed women.MethodsWe used administrative data (2004–2007) from a national sample of 14.4 million commercially insured patients to identify newly diagnosed, early-onset breast cancer cases among women aged 20–40 years (n = 1474). Cox models assessed BRCA1/2 testing, adjusting for covariates and differential lengths of follow-up.ResultsOverall, 30% of women aged 40 years or younger received BRCA1/2 testing. In adjusted analyses, women of Jewish ethnicity were significantly more likely to be tested (hazard ratio = 2.83, 95% confidence interval: 1.52–5.28), whereas black women (hazard ratio = 0.34, 95% 0.18–0.64) and Hispanic women (hazard ratio = 0.52, 95% confidence interval: 0.33–0.81) were significantly less likely to be tested than non-Jewish white women. Those enrolled in a health maintenance organization (hazard ratio = 0.73, 95% confidence interval: 0.54–0.99) were significantly less likely to receive BRCA1/2 testing than those point of service insurance plans. Testing rates increased sharply for women diagnosed in 2007 compared with 2004.ConclusionsIn this national sample of patients with newly diagnosed breast cancer at high risk for BRCA1/2 mutations, genetic assessment was low, with marked racial differences in testing. Genet Med 2011:13(4):349–355.     

Characteristics associated with genetic counseling referral and BRCA1/2 testing among women in a large integrated health system

BackgroundEvidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing.MethodsAn ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate).ResultsAmong the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0–9.6) to report genetic counseling referral.ConclusionIn a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing.Genet Med advance online publication 19 June 2014     

Maternal reports of family history from the National Birth Defects Prevention Study, 1997–2001

PurposeTo assess usefulness of family history information obtained in pediatric practice, we evaluated maternally reported family history data.MethodsWe analyzed family history responses from the National Birth Defects Prevention Study using interview data from mothers of children with birth defects (n = 9,331) and of unaffected liveborn children (n = 3,390) with 1997–2001 estimated delivery dates. We examined the effects of demographic factors, case–control status, and type of defect on birth defect family history reports. Interview information was compared with occurrence of prenatal testing.ResultsAmong case mothers, 1,577 (17%) reported a first- or second-degree relative with a birth defect, compared with 327 (10%) control mothers (odds ratio = 1.91, 95% confidence interval = 1.68–2.16). Reports of affected relatives were also more frequent among mothers who were non-Hispanic white, were 25 years or older, had more than 12 years of education, had an annual household income greater than $20,000, were born in the United States, and completed an English-language interview.ConclusionReporting a family history of birth defects might be influenced by maternal demographic factors, which should be considered in developing pediatric family history tools.     

The association of low socioeconomic status and the risk of having a child with Down syndrome: a report from the National Down Syndrome Project

PurposeAdvanced maternal age and altered recombination are known risk factors for Down syndrome cases due to maternal nondisjunction of chromosome 21, whereas the impact of other environmental and genetic factors is unclear. The aim of this study was to investigate an association between low maternal socioeconomic status and chromosome 21 nondisjunction.MethodsData from 714 case and 977 control families were used to assess chromosome 21 meiosis I and meiosis II nondisjunction errors in the presence of three low socioeconomic status factors: (i) both parents had not completed high school, (ii) both maternal grandparents had not completed high school, and (iii) an annual household income of <$25,000. We applied logistic regression models and adjusted for covariates, including maternal age and race/ethnicity.ResultsAs compared with mothers of controls (n = 977), mothers with meiosis II chromosome 21 nondisjunction (n = 182) were more likely to have a history of one low socioeconomic status factor (odds ratio = 1.81; 95% confidence interval = 1.07–3.05) and ≥2 low socioeconomic status factors (odds ratio = 2.17; 95% confidence interval = 1.02–4.63). This association was driven primarily by having a low household income (odds ratio = 1.79; 95% confidence interval = 1.14–2.73). The same statistically significant association was not detected among maternal meiosis I errors (odds ratio = 1.31; 95% confidence interval = 0.81–2.10), in spite of having a larger sample size (n = 532).ConclusionWe detected a significant association between low maternal socioeconomic status and meiosis II chromosome 21 nondisjunction. Further studies are warranted to explore which aspects of low maternal socioeconomic status, such as environmental exposures or poor nutrition, may account for these results.Genet Med15 9, 698–705.