Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Assessment of the Accuracy of Identification of Selected Disabilities and Conditions in Hospital Discharge Data for Pregnant Women.

BACKGROUND: Linked birth certificate-hospital discharge records are a valuable resource for examining pregnancy outcomes among women with disability conditions. Few studies relying on these data have been able to assess the accuracy of identification of preexisting disability conditions. We assessed the accuracy of International Classification of Diseases version 9 (ICD9) codes for identifying selected physical, sensory, and intellectual conditions that may result in disability. As ICD9 codes were utilized until recently in most states, this information is useful to inform analyses with these records. METHODS: We reviewed 280 of 311 (90%) medical records of pregnant women with disabilities based on ICD9 codes and 390 of 8,337 (5%) records of pregnant women without disabilities who had deliveries at a large university medical center. We estimated sensitivity, specificity, and positive predictive values (PPV) using the medical record as gold standard. We adjusted for verification bias using inverse probability weighting and imputation. RESULTS: The estimated sensitivity of ICD9 codes to identify women with disabilities with deliveries 2009-2012 was 44%; PPV was 98%, improving over time. Although sensitivity was <50% for some conditions, PPVs were 87%-100% for all conditions except intellectual disability (67%). Many physical conditions had complete verification and no underreporting. CONCLUSIONS: These results are helpful for new studies using historical data comparing outcomes among women with and without these conditions and to inform interpretation of results from earlier studies. Assessment of the accuracy of disabilities as identified by ICD version 10 codes is warranted.

Antidepressant continuation in pregnancy and risk of gestational diabetes.

PURPOSE: Previous studies observed modestly higher risk of gestational diabetes (GDM) associated with antidepressant use in pregnancy, potentially due to confounding by indication. We assessed the association of antidepressant continuation in pregnancy with GDM, as well as blood glucose levels, after accounting for confounding. METHODS: We conducted a retrospective cohort study of singleton live births from 2001 to 2014 to women enrolled in Kaiser Permanente Washington, an integrated health care delivery system, utilizing electronic health data and linked Washington State birth records. We required that women have ≥1 antidepressant prescription fills ≤6 months before pregnancy. Women with an antidepressant fill during pregnancy were categorized as "continuers" (n = 1634); those without a fill were "discontinuers" (n = 1211). We calculated relative risks (RRs) for GDM and mean differences in screening blood glucose levels using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including mental health conditions and indicators of mental health severity. RESULTS: Compared with discontinuers, antidepressant continuers had comparable risk of GDM (RR: 1.10; 95% confidence interval [CI], 0.84-1.44) and blood glucose levels (mean difference: 2.3 mg/dL; 95% CI, -1.5 to 6.1 mg/dL). We observed generally similar results for specific antidepressants, with the potential exceptions of risk of GDM associated with sertraline (RR: 1.30; 95% CI, 0.90-1.88) and venlafaxine (RR: 1.52; 95% CI, 0.87-2.68), but neither association was statistically significant. CONCLUSIONS: Our study suggests that overall, women who continue antidepressants in pregnancy are not at increased risk for GDM or higher blood glucose, although further study may be warranted for sertraline and venlafaxine.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

IMPORTANCE: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes. OBJECTIVES: To identify specific birth defect-childhood cancer (BD-CC) associations and characterize cancer risk in children by increasing number of nonchromosomal birth defects. DESIGN, SETTING, AND PARTICIPANTS: This multistate, population-based registry linkage study pooled statewide data on births, birth defects, and cancer from Texas, Arkansas, Michigan, and North Carolina on 10 181 074 children born from January 1, 1992, to December 31, 2013. Children were followed up to 18 years of age for a diagnosis of cancer. Data were retrieved between September 26, 2016, and September 21, 2017, and data analysis was performed from September 2, 2017, to March 21, 2019. EXPOSURES: Birth defects diagnoses (chromosomal anomalies and nonchromosomal birth defects) recorded by statewide, population-based birth defects registries. MAIN OUTCOMES AND MEASURES: Cancer diagnosis before age 18 years, as recorded in state cancer registries. Cox regression models were used to generate hazard ratios (HRs) and 95% CIs to evaluate BD-CC associations and the association between number of nonchromosomal defects and cancer risk. RESULTS: Compared with children without any birth defects, children with chromosomal anomalies were 11.6 (95% CI, 10.4-12.9) times more likely to be diagnosed with cancer, whereas children with nonchromosomal birth defects were 2.5 (95% CI, 2.4-2.6) times more likely to be diagnosed with cancer before 18 years of age. An increasing number of nonchromosomal birth defects was associated with a corresponding increase in the risk of cancer. Children with 4 or more major birth defects were 5.9 (95% CI, 5.3-6.4) times more likely to be diagnosed with cancer compared with those without a birth defect. In the analysis of 72 specific BD-CC patterns, 40 HRs were statistically significant (adjusted P < .05) after accounting for multiple comparisons. Cancers most frequently associated with nonchromosomal defects were hepatoblastoma and neuroblastoma. CONCLUSIONS AND RELEVANCE: Several significant and novel associations were observed between specific birth defects and cancers. Among children with nonchromosomal birth defects, the number of major birth defects diagnosed was significantly and directly associated with cancer risk. These findings could inform clinical treatment for children with birth defects and may elucidate mechanisms that lead to these complex outcomes.

Comprehensive smoke alarm coverage in lower economic status homes: alarm presence, functionality, and placement.

The objectives of this study are to estimate smoke alarm coverage and adherence with national guidelines in low- to mid-value owner-occupied residences, and to identify resident demographic, behavioral, and building characteristics and other fire and burn safety practices associated with smoke alarm utilization. Baseline visits were conducted with 779 households in King County, Washington, for a randomized trial of smoke alarm functionality. Presence, functionality, features, and location of pre-existing smoke alarms were ascertained by staff observation and testing. Household and building descriptors were collected using questionnaires. Households were classified by presence of smoke alarms, functional alarms, and functional and properly mounted alarms placed in hallways and on each floor but not in recommended avoidance locations. Smoke alarms were present in 89%, and functional units in 78%, of households. Only 6-38% met all assessed functionality and placement recommendations. Homes frequently lacked alarms in any bedrooms or on each floor. Building age, but not renovation status, was associated with all dimensions of smoke alarm coverage; post-1980 constructions were 1.7 times more likely to comply with placement recommendations than were pre-1941 homes (95% CI: 1.1-2.6). Respondent education and race/ethnicity, children <5 years, residency duration, number of floors, wood stoves and fireplaces, number of smoke alarms, recency of smoke alarm testing, carbon monoxide monitors, and fire ladders displayed varying relationships with alarm presence, functionality, and placement. Strategies for maintaining smoke alarms in functional condition and improving compliance with placement recommendations are necessary to achieve universal coverage, and will benefit the majority of households.

A comparison of record linkage yield for health research using different variable sets.

As part of a study on childbearing and survival, we linked records of young women with invasive breast cancer identified through three population-based cancer registries, to state birth certificate records. In Michigan prior to 1989, only maternal social security number (SSN) was available for matching; other data became available in 1989 including name, birth date, address, and infant's surname. To examine the quality of the linkage using SSN as the sole matching criterion, we conducted two procedures using data for 1989-1994 to compare linkages identified by SSN, to linkages identified using other available variables. Linkage was conducted using a deterministic approach based on seven variables and 14 steps. In each step a string of relevant variables was created and in successive phases selected variables were substituted or removed with decreasingly stringent requirements. A manual review was done to check for accuracy. Utilizing all available variables, the linkage process yielded 793 matches (live births) among 4496 patients, 780 [98%] of which would have been identified using SSN alone. Five of seven matches identified by SSN were not confirmed by manual review. SSN appears to be fairly accurate for linkage and can be valuable for linking cancer registries to other data sources.