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.

Breastfeeding and risk of childhood brain tumors: a report from the Childhood Cancer and Leukemia International Consortium.

PURPOSE: Studies report mixed findings regarding the association of breastfeeding with childhood brain tumors (CBT), the leading causes of cancer-related mortality in young people. Our objective was to determine whether breastfeeding is associated with CBT incidence. METHODS: We pooled data on N = 2610 cases with CBT (including 697 cases with astrocytoma, 447 cases with medulloblastoma/primitive neuroectodermal tumor [PNET], 167 cases with ependymoma) and N = 8128 age- and sex-matched controls in the Childhood Cancer and Leukemia International Consortium. We computed unconditional logistic regression models to estimate the odds ratio (OR) and 95% confidence interval (CI) of CBT, astrocytoma, medulloblastoma/PNET, and ependymoma according to breastfeeding status, adjusting for study, sex, mode of delivery, birthweight, age at diagnosis/interview, maternal age at delivery, maternal educational attainment, and maternal race/ethnicity. We evaluated any breastfeeding versus none and breastfeeding ≥ 6 months versus none. We subsequently performed random effects meta-analysis to confirm our findings, identify potential sources of heterogeneity, and evaluate for outliers or influential studies. RESULTS: Breastfeeding was reported by 64.8% of control mothers and 64.5% of case mothers and was not associated with CBT (OR 1.04, 95% CI 0.94-1.15), astrocytoma (OR 1.01, 95% CI 0.87-1.17), medulloblastoma/PNET (OR 1.11, 95% CI 0.93-1.32), or ependymoma (OR 1.06, 95% CI 0.81-1.40). Results were similar when we restricted to breastfeeding ≥ 6 months and in meta-analyses. CONCLUSION: Our data suggest that breastfeeding does not protect against CBT.

Socioeconomic Factors and Adherence to Health Care Recommendations in Adolescent and Young Adult Cancer Survivors.

Purpose: The majority of adolescent and young adult (AYA) cancer survivors do not receive recommended health care surveillance after therapy. We used cross-sectional survey data to evaluate the impact of income, education, marital status, and insurance on health care adherence among AYA survivors. Methods: Eligible survivors were 18-39 years at diagnosis with invasive malignancy, 1-5 years from therapy completion. Online surveys assessed sociodemographic factors and self-report of completion of recommended health care services. Diagnosis and treatment data were abstracted from medical records. Multivariable logistic regression calculated odds ratios (ORs) and 95% confidence intervals (CIs) for adherence in relation to socioeconomic status and support. Results: Of 344 participants, 36% were adherent to at least 80% of recommendations. Adherence varied by cancer type: 34% for breast cancer, 52% for leukemia/lymphoma, 23% for other tumors. Adherence rates were similar among White, Asian, and Hispanic/Latinx patients. Lower adherence was associated with lower education (OR: 0.43; 95% CI: 0.23-0.80 for <4-year college degree) and lower annual income (OR: 0.51; 95% CI: 0.28-0.95 for $41,000-$80,000; OR: 0.40; 95% CI: 0.19-0.86 for ≤$40,000). Adherence decreased with decreasing income levels among those who were 1 to less than 3 years after diagnosis (OR: 0.25; 95% CI: 0.07-0.93 for $81,000-$120,000; OR: 0.24; 95% CI: 0.07-0.84 for $41,000-$80,000; OR: 0.13; 95% CI: 0.03-0.60 for ≤$40,000). Conclusion: Risk of nonadherence to health care guidelines was associated with lower income and lower education among AYA cancer survivors. Identification of these risks and related barriers to adherence in AYA survivors will inform interventions designed to meet needs of these high-risk groups, particularly during the first years after diagnosis. Trial Registration: NCT02192333.

Birth Outcomes and Rehospitalizations Among Pregnant Women With Rheumatoid Arthritis and Systemic Lupus Erythematosus and Their Offspring.

OBJECTIVE: To compare obstetric/birth outcomes and rehospitalization among women with and without rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) and their infants. METHODS: This population-based retrospective cohort study identified women with RA (n = 1,223) and SLE (n = 1,354) and unexposed women with singleton births 1987-2014 in Washington State in linked vital hospital discharge records. Outcomes, including cause-specific hospitalizations <2 years postpartum, were compared by estimating adjusted relative risks (RRs) and cause-specific rehospitalization hazard ratios (HRs) with 95% confidence intervals (95% CIs). RESULTS: We observed increased risks of several adverse outcomes; RRs were often greatest for SLE. Women with RA/SLE more often required rehospitalization, most notably at <6 months postpartum (RA: 4% versus 2%; RR 2.22 [95% CI 1.62-3.04]; SLE: 6% versus 2%; RR 2.78 [95% CI 2.15-3.59]). Maternal postpartum rehospitalization was greatest for musculoskeletal conditions (RA: HR 19.1 [95% CI 13.6-26.8]; SLE: HR 29.8 [95% CI 22.1-40.1]). Infants of women with SLE more often had malformations (9% versus 6%; RR 1.46 [95% CI 1.21-1.75]), and increased mortality at <2 years (RR 2.11 [95% CI 1.21-3.67]). Infants of women with SLE also experienced more frequent rehospitalizations in their first year of life. CONCLUSION: Women with RA or SLE and their infants experienced adverse outcomes, particularly infants of women with SLE. Maternal/infant rehospitalization was more common; most marked in the early months postpartum. Close follow-up during these time periods is crucial to minimize adverse outcomes.

A Population-Based Study of the Long-Term Risk of Infections Associated With Hospitalization in Childhood Cancer Survivors.

PURPOSE: Infections pose a significant risk during therapy for childhood cancer. However, little is known about the risk of infection in long-term survivors of childhood cancer. METHODS: We performed a retrospective observational study of children and adolescents born in Washington State diagnosed with cancer before age 20 years and who survived at least 5 years after diagnosis. Survivors were categorized as having a hematologic or nonhematologic malignancy and were matched to individuals without cancer in the state birth records by birth year and sex with a comparator:survivor ratio of 10:1. The primary outcome was incidence of any infection associated with a hospitalization using diagnostic codes from state hospital discharge records. Incidence was reported as a rate (IR) per 1,000 person-years. Multivariate Poisson regression was used to calculate incidence rate ratios (IRR) for cancer survivors versus comparators. RESULTS: On the basis of 382 infection events among 3,152 survivors and 771 events among 31,519 comparators, the IR of all hospitalized infections starting 5 years after cancer diagnosis was 12.6 (95% CI, 11.4 to 13.9) and 2.4 (95% CI, 2.3 to 2.6), respectively, with an IRR 5.1 (95% CI, 4.5 to 5.8). The survivor IR during the 5- to 10-year (18.1, 95% CI, 15.9 to 20.5) and > 10-year postcancer diagnosis (8.3, 95% CI, 7.0 to 9.7) periods remained greater than comparison group IRs for the same time periods (2.3, 95% CI, 2.1 to 2.6 and 2.5, 95% CI, 2.3 to 2.8, respectively). When potentially vaccine-preventable infections were evaluated, survivors had a greater risk of infection relative to comparators (IRR, 13.1; 95% CI, 7.2 to 23.9). CONCLUSION: Infectious complications continue to affect survivors of childhood cancer many years after initial diagnosis. Future studies are needed to better understand immune reconstitution to determine specific factors that may mitigate this risk.

Population-Based Impact of Rurality and Neighborhood-Level Socioeconomic Disadvantage on Pediatric Cancer Mortality in Washington State.

BACKGROUND: Childhood cancer-related mortality differs by socioeconomic factors, but the impact of residential location, including rurality and neighborhood-level socioeconomic disadvantage, is not well-characterized. METHODS: This retrospective cohort study linked Washington State cancer registry data (1992-2013) to state birth (1974-2013) and death records (1992-2013) to identify residents <20 years diagnosed with cancer (n = 4,306). Census-based rural-urban commuting area codes and Area Deprivation Index (ADI) defined rural residence and neighborhood socioeconomic disadvantage at time of cancer diagnosis, respectively. Neighborhoods in the highest state ADI quintile were classified as the most disadvantaged. Kaplan-Meier estimates and Cox hazards models, adjusted for key characteristics, were used to compare mortality by rural and ADI classification. RESULTS: Five-year overall survival for children from non-rural low ADI neighborhoods (referent) was 80.9%±0.8%, versus 66.4%±2.9% from non-rural high ADI neighborhoods, 69.4%±3.8% from rural low ADI neighborhoods, and 66.9%±3.8% from rural high ADI neighborhoods (P < 0.01 for each comparison versus referent). Compared with the referent group, children from comparator neighborhoods had a greater mortality risk: Rural low ADI [hazard ratio (HR), 1.50; 95% confidence interval (CI), 1.12-2.02], rural high ADI (HR, 1.53; 95% CI, 1.16-2.01), and non-rural high ADI (HR, 1.64; 95% CI, 1.32-2.04). Associations of ADI and rurality with mortality varied in sub-analyses by cancer type. CONCLUSIONS: Children with cancer living in rural and/or socioeconomically disadvantaged neighborhoods at diagnosis experienced greater mortality relative to those without either factor. IMPACT: Future investigation is needed to examine how rurality and poverty potentially impact healthcare utilization and health-related outcomes in pediatric oncology.

Morbidity and rehospitalization postpartum among women with epilepsy and their infants: A population-based study.

OBJECTIVE: We compared the relative occurrence of selected pregnancy outcomes and postpartum rehospitalizations among women with and without epilepsy and their infants. Using linked vital-hospital discharge records of women with deliveries in Washington State 1987-2014, comparisons were made overall, by epilepsy type, and by time periods related to antiepileptic drug (AED) marketing changes. METHODS: This population-based retrospective cohort study identified women with, and without epilepsy per diagnosis codes in the hospital discharge record from among all deliveries during 1987-2014 to examine maternal and infant outcomes, rehospitalization and mortality <2 years postpartum. Relative risks (RRs) and 95 % confidence intervals (CI) overall, and by epilepsy type were calculated using Poisson regression. We assessed the validity of epilepsy identification based on diagnosis codes by conducting a medical chart review for a sample of women. RESULTS: Women with epilepsy had increased risks of preeclampsia (RR 1.23; 95 % CI 1.08-1.41) and gestational diabetes (RR 1.18; 95 % CI 1.02-1.36). Their infants had increased malformation (RR 1.23; 95 % C: 1.08-1.42) and small for gestational age (SGA, RR 1.39; 95 % CI 1.25-1.54) risks, and were nearly three times as likely to not be breastfed. Affected mothers (RR 5.25; 95 % CI 2.46-11.23) and their infants (RR 1.64, 95 % CI 1.41-1.89) required more ICU admissions during the delivery hospitalizations, and more postpartum rehospitalization, with greatest risk in the first six months. Maternal mortality < 2 years after delivery was increased (RR 7.11; 95 % CI 2.47-20.49). Increased risks were observed for all epilepsy subtypes for nearly all outcomes examined. Risks of preterm delivery and low birthweight increased over time (p <.05). Suggestive, but not statistically significant temporal decreases in risks of gestational diabetes and malformations and increased risk of preterm labor were noted. We observed high sensitivity of diagnosis codes for identifying pregnant women with epilepsy. CONCLUSION: These population-based results emphasize the need for frequent postpartum monitoring of women with epilepsy. Increases in risks of low birthweight and preterm delivery over time are of concern. Possible temporal changes in other outcomes warrant further investigation.

Mother's and Father's Serious Mental Illness and Risk of Child Injury in a Taiwanese Birth Cohort.

Objective: Parental serious mental illness (SMI) is associated with childhood injury. This study investigated whether child injury risk differs according to which parent is affected, SMI diagnosis, or timing of SMI onset.Methods: This cohort study included 1,999,322 singletons born in 2004-2014 identified from the national Taiwanese registries. General estimating equation Poisson models were used to estimate incidence rate ratios (IRRs) of injury events and hospitalizations before the age of 5 years among children according to which parent was affected, SMI diagnosis (schizophrenia [ICD-9-CM codes: 295, 297, 298.3, 298.4, 298.9], bipolar disorder [296.00-296.16, 296.40-296.81, 296.89-296.99, 298.1, 648.4], or major depressive disorder [MDD; 296.20-296.36, 296.82, 298.0]), and timing of diagnosis (before or after childbirth, as a proxy of timing of onset). Data analysis was performed on data obtained from April 20, 2017, to May 6, 2020.Results: Relative to unexposed children, the IRRs of injury hospitalizations for children with two SMI-affected parents, maternal SMI only, and paternal SMI only were 1.85 (95% CI, 1.38-2.48), 1.58 (95% CI, 1.48-1.68), and 1.34 (95% CI, 1.23-1.46), respectively. The IRRs of injury hospitalizations for maternal schizophrenia, bipolar disorder, and MDD were 2.09 (95% CI, 1.82-2.40), 1.77 (95% CI, 1.56-2.00), and 1.38 (95% CI, 1.26-1.50), respectively. The IRRs for paternal schizophrenia, bipolar disorder, and MDD were 1.39 (95% CI, 1.20-1.60), 1.61 (95% CI, 1.39-1.87), and 1.19 (95% CI, 1.05-1.36), respectively. The magnitude of excess risk was similar for children whose parent(s) experienced SMI diagnosed before and after childbirth.Conclusions: We found children with two SMI-affected parents or at least one parent with schizophrenia or bipolar disorder to be at greatest risk of severe injury requiring hospitalization. These parents may benefit from extra parenting support and injury prevention coaching.

Accelerated epigenetic aging in newborns with Down syndrome.

Accelerated aging is a hallmark of Down syndrome (DS), with adults experiencing early-onset Alzheimer's disease and premature aging of the skin, hair, and immune and endocrine systems. Accelerated epigenetic aging has been found in the blood and brain tissue of adults with DS but when premature aging in DS begins remains unknown. We investigated whether accelerated aging in DS is already detectable in blood at birth. We assessed the association between age acceleration and DS using five epigenetic clocks in 346 newborns with DS and 567 newborns without DS using Illumina MethylationEPIC DNA methylation array data. We compared two epigenetic aging clocks (DNAmSkinBloodClock and pan-tissue DNAmAge) and three epigenetic gestational age clocks (Haftorn, Knight, and Bohlin) between DS and non-DS newborns using linear regression adjusting for observed age, sex, batch, deconvoluted blood cell proportions, and genetic ancestry. Targeted sequencing of GATA1 was performed in a subset of 184 newborns with DS to identify somatic mutations associated with transient abnormal myelopoiesis. DS was significantly associated with increased DNAmSkinBloodClock (effect estimate = 0.2442, p < 0.0001), with an epigenetic age acceleration of 244 days in newborns with DS after adjusting for potential confounding factors (95% confidence interval: 196-292 days). We also found evidence of epigenetic age acceleration associated with somatic GATA1 mutations among newborns with DS (p = 0.015). DS was not associated with epigenetic gestational age acceleration. We demonstrate that accelerated epigenetic aging in the blood of DS patients begins prenatally, with implications for the pathophysiology of immunosenescence and other aging-related traits in DS.

Hospitalization and Mortality Outcomes Among Childhood Cancer Survivors by Race, Ethnicity, and Time Since Diagnosis.

Importance: Cancer outcomes are relatively poor in adults who belong to minoritized racial and ethnic groups. Survival and long-term outcomes by race and ethnicity in individuals with childhood cancers are less studied. Objective: To evaluate survival and hospitalization among American Indian and Alaska Native, Asian, Black, and Hispanic children compared with non-Hispanic White children with cancer. Design, Setting, and Participants: This cohort study evaluated all individuals born in Washington State who were younger than 20 years (hereafter referred to as children) and had been diagnosed with cancer during 1987 to 2012, with follow-up ranging from 1 to 27 years. The data subset was built in 2019, and statistical analyses were completed in January 2022. Exposures: Race and ethnicity. Main Outcomes and Measures: Mortality and hospitalization events for all other racial and ethnic groups relative to non-Hispanic White children estimated by Cox proportional hazards regressions for the first 5 years after diagnosis and among cancer survivors 5 or more years after diagnosis. Results: A total of 4222 children (mean [SD] age, 8.4 [6.4] years; 2199 [52.1%] male; 113 American Indian and Alaska Native [2.7%], 311 Asian [7.4%], 196 Black [4.6%], 387 Hispanic [9.2%], and 3215 non-Hispanic White [76.1%]) with cancer diagnosed at younger than 20 years during 1987 to 2012 were included. Mortality was similar across all groups. Compared with non-Hispanic White survivors at less than 5 years after diagnosis, there were no greatly increased hazard ratios (HRs) for hospitalization. Among survivors at 5 or more years after diagnosis, hospitalization HRs were 1.7 (95% CI, 1.0-3.0) for American Indian and Alaska Native survivors and 1.5 (95% CI, 0.9-2.4) for Black survivors. Significantly increased HRs among Hispanic children were observed for infection-related (HR, 1.4; 95% CI, 1.2-1.6), endocrine-related (HR, 1.3; 95% CI, 1.1-1.6), hematologic-related (HR, 1.3; 95% CI, 1.1-1.5), respiratory-related (HR, 1.3; 95% CI, 1.0-1.5), and digestive-related (HR, 1.2; 95% CI, 1.0-1.5) conditions. American Indian and Alaskan Native children had increased HRs for infection-related (HR, 2.3; 95% CI, 1.2-4.5), hematologic-related (HR, 3.0; 95% CI, 1.4-6.5), and digestive-related (HR, 2.6; 95% CI, 1.3-5.4) conditions. Both American Indian and Alaska Native (HR, 3.6; 95% CI, 1.4-9.0) and Black (HR, 2.5; 95% CI, 1.2-5.5) children had increased mental health-related hospitalizations and death. Conclusions and Relevance: In this cohort study, disproportionately increased long-term risks of hospitalization for physical and mental conditions may have contributed to worse outcomes by race. A key component to bridging the morbidity gap by race is improved understanding of reasons for greater cause-specific hospitalizations in some groups, with development of culturally appropriate intervention strategies.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention.

Sex differences in associations between birth characteristics and childhood cancers: a five-state registry-linkage study.

BACKGROUND: There is a well-recognized male excess in childhood cancer incidence; however, it is unclear whether there is etiologic heterogeneity by sex when defined by epidemiologic risk factors. METHODS: Using a 5-state registry-linkage study (cases n = 16,411; controls n = 69,816), we estimated sex-stratified odds ratios (OR) and 95% confidence intervals (95% CI) between birth and demographic characteristics for 16 pediatric cancers. Evidence of statistical interaction (p-interaction < 0.01) by sex was evaluated for each characteristic in each cancer. RESULTS: Males comprised > 50% of cases for all cancers, except Wilms tumor (49.6%). Sex interacted with a number of risk factors (all p-interaction < 0.01) including gestational age for ALL (female, 40 vs. 37-39 weeks OR: 0.84, 95% CI 0.73-0.97) and ependymoma (female, 40 vs. 37-39 OR: 1.78, 95% CI 1.14-2.79; female, ≥ 41 OR: 2.01. 95% CI 1.29-3.14), birth order for AML (female, ≥ 3rd vs. 1st OR: 1.39, 95% CI 1.01-1.92), maternal education for Hodgkin lymphoma (male, any college vs. < high school[HS] OR: 1.47, 95% CI 1.03-2.09) and Wilms tumor (female, any college vs. HS OR: 0.74, 95% CI 0.59-0.93), maternal race/ethnicity for neuroblastoma (male, black vs. white OR: 2.21, 95% CI 1.21-4.03; male, Hispanic vs. white OR: 1.86, 95% CI 1.26-2.75; female, Asian/Pacific Islander vs. white OR: 0.28, 95% CI 0.12-0.69), and paternal age (years) for hepatoblastoma in males (< 24 vs. 25-29 OR: 2.17, 95% CI 1.13-4.19; ≥ 35 vs. 25-29 OR: 2.44, 95% CI 1.28-4.64). CONCLUSIONS: These findings suggest etiologic heterogeneity by sex for childhood cancers for gestational age, maternal education, and race/ethnicity and paternal age.

Association of Antidepressant Continuation in Pregnancy and Infant Birth Weight.

PURPOSE: The aim of the study was to evaluate the association of antidepressant continuation in pregnancy with infant birth weight among women using antidepressants before pregnancy. METHODS: This retrospective cohort study used electronic health data linked with state birth records. We identified singleton live births (2001-2014) to enrolled women with 1 or more antidepressant prescriptions filled 6 months or less before pregnancy, including "continuers" (≥1 antidepressant fills during pregnancy, n = 1775) and "discontinuers" (no fill during pregnancy, n = 1249). We compared birth weight, small or large for gestational age (SGA or LGA), low birth weight (LBW; <2500 g), and macrosomia (>4500 g) between the 2 groups, using inverse probability of treatment weighting to account for pre-pregnancy characteristics, including mental health conditions. RESULTS: After weighting, infants born to antidepressant continuers weighed 71.9 g less than discontinuers' infants (95% confidence interval [CI], -115.5 to -28.3 g), with a larger difference for female infants (-106.4 g; 95% CI, -164.6 to -48.1) than male infants (-48.5 g; 95% CI, -107.2 to 10.3). For female infants, SGA risk was greater in continuers than discontinuers (relative risk [RR],1.54; 95% CI, 1.02 to 2.32). Low birth weight risk was greater in continuers with 50% or more of days covered (RR, 1.69; 95% CI, 1.11 to 2.58) and exposure in the second trimester (RR, 1.53; 95% CI, 1.02 to 2.29), as compared with discontinuers. CONCLUSIONS: Depending on infant sex, as well as duration and timing of use, continuation of antidepressant use during pregnancy may be associated with lower infant birth weight, with corresponding increases in LBW and SGA.

Hospitalization and mortality outcomes in the first 5 years after a childhood cancer diagnosis: a population-based study.

PURPOSE: Children with cancer are frequently hospitalized. However, hospitalization and death by disease category are not well defined < 5 years from diagnosis. METHODS: We conducted a retrospective cohort study using linked cancer registry-hospital discharge-vital records to identify cancer cases < 20 years at diagnosis during 1987-2012 (n = 4,567) and comparison children without cancer, matched on birth year and sex (n = 45,582). Data linkage identified serious morbidities resulting in cancer- and non-cancer-related hospitalizations or deaths < 5 years from diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to compare relative hospitalization and mortality by disease category and after excluding cancer-related outcomes. Among cancer cases, relative risks of these outcomes for children with solid tumors compared with children with leukemia/lymphoma were also estimated. RESULTS: Greater rates of all-cause hospitalization (281.5/1,000 vs. 6.2/1,000 person years) and death (40.7/1,000 vs. 0.15/1,000 person years) were observed in childhood cancer cases than comparators and across all diagnosis categories. Increased hospitalization (31.0/1,000 vs. 6.2/1,000 person years; HR 5.0, 95% CI 4.5-5.5) and death (1.0/1,000 vs. 0.15/1,000 person years; HR 10.4, 95% CI 5.6-19.1) rates remained when cancer-related outcomes were excluded. Although HRs for hospitalization and death did not differ greatly by treatment era, absolute rates of hospitalization were greater (1987-1999: 233.3/1,000; 2000-2012: 320.0/1,000 person years) and death were lesser (1987-1999: 46.3/1,000; 2000-2012: 36.8/1,000 person years) in the later treatment era among cases. Children with solid tumors were less likely to have a cancer-related hospitalization than were those with leukemia/lymphoma (RR 0.91, 95% CI 0.84-0.98). CONCLUSION: Even after excluding cancer-related diagnoses, children with cancer experience greater rates of hospitalization and death in all disease categories. Results may guide future toxicity mitigation initiatives and inform anticipatory guidance for families of children with cancer.

Pregnancy outcomes among visually impaired women in Washington State, 1987-2014.

BACKGROUND: Women with visual impairment may have reduced ability to access standard care resources, however, information on their pregnancy and neonatal outcomes is limited. OBJECTIVE: To assess risk of adverse pregnancy and neonatal outcomes among visually impaired women in Washington State from 1987 to 2014. METHODS: We conducted a retrospective cohort study using linked Washington State birth/fetal death hospital discharge records to compare outcomes among women with and without visual impairment noted at their delivery hospitalization. Pregnancy conditions and outcomes evaluated included gestational diabetes, pre-eclampsia, labor induction and cesarean delivery. Neonatal outcomes included preterm delivery and birth weight <2500 g. We assessed length of maternal and infant delivery hospitalization. We performed Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CIs) for each outcome, adjusting for year of delivery, maternal age, and parity. RESULTS: Most adverse pregnancy and neonatal outcomes were similar for visually impaired (N = 232) and comparison women (N = 2362). However, visually impaired women had increased risks of severe pre-eclampsia (RR 3.77, 95% CI 1.69-8.43), labor induction (RR 1.33, 95% CI 1.10-1.61) and preterm delivery (RR 1.60, 95% CI 1.06-2.42). They were also more likely to have delivery hospitalizations of 3 or more days following a vaginal (RR 1.86, 95% CI 1.41-2.47). Among cesarean deliveries, infants of visually impaired women had increased risk (RR 1.24, 95% CI 1.02-1.51) of hospitalization for 3 or more days postpartum. CONCLUSION: Our findings may be useful for obstetric providers in counseling their visually impaired patients.

Maternal Gestational Weight Gain in Relation to Antidepressant Continuation in Pregnancy.

OBJECTIVE: Both excessive and inadequate gestational weight gain (GWG) are associated with adverse health outcomes for the woman and her child. Antidepressant use in pregnancy could affect GWG, based on evidence in nonpregnant women that some antidepressants may cause weight gain and others weight loss. Previous studies of antidepressant use and GWG were small with limited ability to account for confounding, including by maternal mental health status and severity. We assessed the association of antidepressant continuation in pregnancy with GWG among women using antidepressants before pregnancy. STUDY DESIGN: Our retrospective cohort study included singleton livebirths from 2001 to 2014 within Kaiser Permanente Washington, an integrated health care system. Data were obtained from electronic health records and linked Washington State birth records. Among women with ≥1 antidepressant fill within 6 months before pregnancy, women who filled an antidepressant during pregnancy were considered "continuers;" women without a fill were "discontinuers." We calculated mean differences in GWG and relative risks (RR) of inadequate and excessive weight gain based on Institute of Medicine guidelines. Using inverse probability of treatment weighting with generalized estimating equations, we addressed differences in maternal characteristics, including mental health conditions. RESULTS: Among the 2,887 births, 1,689 (59%) were to women who continued antidepressants in pregnancy and 1,198 (42%) were to discontinuers. After accounting for confounding, continuers had similar weight gain to those who discontinued (mean difference: 1.3 lbs, 95% confidence interval [CI]: -0.1 to 2.8 lbs) and similar risks of inadequate and excessive GWG (RR: 0.95, 95% CI: 0.80-1.14 and RR: 1.06, 95% CI: 0.98-1.14, respectively). Findings were comparable for specific antidepressants and trimesters of exposure. CONCLUSION: We did not find evidence that continuation of antidepressants in pregnancy led to differences in GWG. KEY POINTS: · Antidepressant use is associated with weight change in nonpregnant populations.. · Prior evidence on whether antidepressant use in pregnancy affects gestational weight gain is sparse.. · We accounted for confounding by characteristics such as mental health conditions and their severity.. · We found no association between pregnancy antidepressant continuation and gestational weight gain..

Association of Parental Mental Illness With Child Injury Occurrence, Hospitalization, and Death During Early Childhood.

Importance: Injury is a leading cause of childhood morbidity and mortality worldwide. Serious mental illness (SMI) is a major contributor to the global burden of disease. Objective: To compare injury event rates in children from birth to 5 years of age among Taiwanese children with and without parents with SMI, including schizophrenia, bipolar disorder, and major depressive disorder. Design, Setting, and Participants: This population-based, retrospective cohort study of an 11-year Taiwanese birth cohort used data from the Taiwan National Health Insurance Research Database (covering 99% of Taiwanese citizens), the Maternal and Child Health Database, and birth and death certificate databases. The study included 1 999 322 singletons with Taiwanese citizenship born from January 1, 2004, to December 31, 2014, and followed up from birth to their fifth birthday, December 31, 2014, or the date of death, yielding a total of 7 741 026 person-years. Data analysis was performed from April 20, 2017, to September 24, 2019. Exposures: Physician-diagnosed parental SMI defined using outpatient and inpatient records from 6 years before the child's birth to 5 years after delivery. Main Outcome and Measures: Rates of medically attended injury events, injury hospitalization, and injury death retrieved from outpatient records, inpatient records, and death certificates. Generalized estimating equation for log-linear models estimated injury incidence rate ratios (IRRs) comparing parental SMI-exposed children and unexposed children. Results: The study cohort included 1 999 322 singletons (52.1% males without parental SMI and 52.2% males with parental SMI). Incidence rates of child injury-related outcomes were higher among children exposed to parental SMI (294.8 injury events per 1000 person-years) compared with children who were unexposed (256.1 injury events per 1000 person-years). After adjustment for sociodemographic factors, children with parental SMI had higher rates of injury events (IRR, 1.14; 95% CI, 1.13-1.15), injury hospitalization (IRR, 1.49; 95% CI, 1.42-1.57), and injury death (IRR, 1.82; 95% CI, 1.38-2.39) compared with unexposed children. The results were confirmed in sensitivity analyses. Appendicitis, a negative control outcome, was not associated with parental SMI (IRR, 1.10; 95% CI, 0.94-1.28). In addition, children with and without parental SMI had similar patterns of preventive health care. The mean (SD) number of prenatal visits was 8.09 (2.50) for children with parental SMI and 8.17 (2.47) among unaffected children. The mean (SD) number of well-child visits was 5.70 (2.24) for children with parental SMI and 5.80 (2.21) among unaffected children. Conclusions and Relevance: In this study, children with parental SMI had increased risk of injury, particularly serious injury. Excess risk may be reduced by providing effective mental health treatment, parenting support, and home safety education to parents with SMI who are raising young children.

Late infectious complications in hematopoietic cell transplantation survivors: a population-based study.

Few studies have compared the incidence of infections occurring ≥2 years after hematopoietic cell transplant (HCT) with other cancer patients and the general population. In this study, ≥2-year HCT survivors who were Washington residents treated from 1992 through 2009 (n = 1792; median age, 46 years; 52% allogeneic; 90% hematologic malignancies) were matched to individuals from the state cancer registry (n = 5455, non-HCT) and driver's license files (n = 16 340; Department of Licensing [DOL]). Based on hospital and death registry codes, incidence rate ratios (IRRs; 95% confidence interval [CI]) of infections by organism type and organ system were estimated using Poisson regression. With 7-year median follow-up, the incidence rate (per 1000 person-years) of all infections was 65.4 for HCT survivors vs 39.6 for the non-HCT group (IRR, 1.6; 95% CI, 1.3-1.9) and 7.2 for DOL (IRR, 10.0; 95% CI, 8.3-12.1). Bacterial and fungal infections were each 70% more common in HCT vs non-HCT cancer survivors (IRR, 1.7; P < .01), whereas the risk for viral infection was lower (IRR, 1.4; P = .07). Among potentially vaccine-preventable organisms, the IRR was 3.0 (95% CI, 2.1-4.3) vs the non-HCT group. Although the incidences of all infections decreased with time, the relative risk in almost all categories remained significantly increased in ≥5-year HCT survivors vs other groups. Risk factors for late infection included history of relapse and for some infections, history of chronic graft-versus-host disease. Providers caring for HCT survivors should maintain vigilance for infections and ensure adherence to antimicrobial prophylaxis and vaccination guidelines.

Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State.

Background: High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia.Material and methods: In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia.Results: Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (≥4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8).Conclusion: This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.