OBJECTIVE: The purpose of this study was to determine whether women with multiple sclerosis who deliver singleton infants are more likely to have pregnancy or delivery complications or to have ...infants with low birth weight, preterm gestation, or malformations than women without multiple sclerosis and to compare their need for rehospitalization during the 2 years after delivery. Study Design: This was a population-based cohort study that used Washington State linked birth certificate-hospital discharge records for singleton births from 1987 through 1996. Pregnancy course, birth outcomes, and need for rehospitalization within 2 years after delivery were compared for 198 women with multiple sclerosis and a comparison group of 1584 women. RESULTS: With the exception of maternal anemia, women with multiple sclerosis were no more likely to have pregnancy or delivery complications, nor were their infants more likely to be low birth weight or preterm or to have malformations. Affected women were, however, twice as likely to be rehospitalized during the 3 months after delivery. CONCLUSION: The increased risk of rehospitalization emphasizes a need for strong support systems and close monitoring during the 3 months after delivery. (Am J Obstet Gynecol 2002;186:446-52.)
Objective: Major depressive disorder (MDD) occurs frequently in adolescents, but the neurobiology of depression in youth is poorly understood. Structural neuroimaging studies in both adult and ...pediatric populations have implicated frontolimbic neural networks in the pathophysiology of MDD. Diffusion tensor imaging (DTI), which measures white matter (WM) microstructure, is a promising tool for examining neural connections and how they may be abnormal in MDD. Method: We used two separate approaches to analyze DTI data in adolescents with MDD (n = 14) compared with healthy volunteers (n = 14). Results: The first, hypothesis-driven approach was to use probabilistic tractography to delineate tracts arising from the subgenual anterior cingulate cortex (ACC). Adolescents with MDD demonstrated lower fractional anisotropy (FA) in the WM tract connecting subgenual ACC to amygdala in the right hemisphere. The second, exploratory approach was to conduct a voxelwise comparison of FA. This analysis revealed 10 clusters where adolescents with MDD had significantly lower (uncorrected) FA than the healthy group within WM tracts including right and left uncinate and supragenual cingulum. Conclusions: These preliminary data support the hypothesis that altered WM microstructure in frontolimbic neural pathways may contribute to the pathophysiology of MDD in adolescents. (Contains 3 figures and 3 tables.)
Household firearms are associated with an elevated risk of firearm death to occupants in the home. Many organizations and health authorities advocate locking firearms and ammunition to prevent access ...to guns by children and adolescents. The association of these firearm storage practices with the reduction of firearm injury risk is unclear.
To measure the association of specific household firearm storage practices (locking guns, locking ammunition, keeping guns unloaded) and the risk of unintentional and self-inflicted firearm injuries.
Case-control study of firearms in events identified by medical examiner and coroner offices from 37 counties in Washington, Oregon, and Missouri, and 5 trauma centers in Seattle, Spokane, and Tacoma, Wash, and Kansas City, Mo. CASES AND CONTROLS: Case firearms were identified by involvement in an incident in which a child or adolescent younger than 20 years gained access to a firearm and shot himself/herself intentionally or unintentionally or shot another individual unintentionally. Firearm assaults and homicides were excluded. We used records from hospitals and medical examiners to ascertain these incidents. Using random-digit dial telephone sampling, control firearms were identified by identification of eligible households with at least 1 firearm and children living or visiting in the home. Controls were frequency matched by age group and county.
The key exposures of interest in this study were: (1) whether the subject firearm was stored in a locked location or with an extrinsic lock; (2) whether the firearm was stored unloaded; (3) whether the firearm was stored both unloaded in a locked location; (4) whether the ammunition for the firearm was stored separately; and (5) whether the ammunition was stored in a locked location. Data regarding the storage status of case and control guns were collected by interview with respondents from the households of case and control firearms.
We interviewed 106 respondents with case firearms and 480 with control firearms. Of the shootings associated with the case firearms, 81 were suicide attempts (95% fatal) and 25 were unintentional injuries (52% fatal). After adjustment for potentially confounding variables, guns from case households were less likely to be stored unloaded than control guns (odds ratio OR, 0.30; 95% confidence interval CI, 0.16-0.56). Similarly, case guns were less likely to be stored locked (OR, 0.27; 95% CI, 0.17-0.45), stored separately from ammunition (OR, 0.45; 95% CI, 0.34-0.93), or to have ammunition that was locked (OR, 0.39; 95% CI, 0.23-0.66) than were control guns. These findings were consistent for both handguns and long guns and were also similar for both suicide attempts and unintentional injuries.
The 4 practices of keeping a gun locked, unloaded, storing ammunition locked, and in a separate location are each associated with a protective effect and suggest a feasible strategy to reduce these types of injuries in homes with children and teenagers where guns are stored.
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.
What's new?
Little is known about whether nonchromosomal birth defects serve etiological roles in childhood leukemia. Birth defects potentially associated with childhood leukemia include congenital disorders affecting the heart and circulatory system, nervous system, or digestive system. Here, the authors sought to identify associations between childhood leukemia and nonchromosomal birth defects using data from the Childhood Cancer and Leukemia International Consortium. Certain defects, including those of the circulatory, nervous and digestive systems, were strongly associated with increased risk of leukemia. The newly described associations open the way to better understanding links between nonchromosomal birth defects, genetic and environmental factors and increased leukemia susceptibility.
Objective: We propose and develop a novel biclustering (N-BiC) approach for performing N-way biclustering of neuroimaging data. Our approach is applicable to an arbitrary number of features from both ...imaging and behavioral data (e.g., symptoms). We applied it to structural MRI data from patients with schizophrenia. Methods: It uses a source-based morphometry approach i.e., independent component analysis of gray matter segmentation maps to decompose the data into a set of spatial maps, each of which includes regions that covary among individuals. Then, the loading parameters for components of interest are entered to an exhaustive search, which incorporates a modified depth-first search technique to carry out the biclustering, with the goal of obtaining submatrices where the selected rows (individuals) show homogeneity in their expressions of selected columns (components) and vice versa. Results: Findings demonstrate that multiple biclusters have an evident association with distinct brain networks for the different types of symptoms in schizophrenia. The study identifies two components: inferior temporal gyrus (16) and brainstem (7), which are related to positive (distortion/excess of normal function) and negative (diminution/loss of normal function) symptoms in schizophrenia, respectively. Conclusion: N-BiC is a data-driven method of biclustering MRI data that can exhaustively explore relationships/substructures from a dataset without any prior information with a higher degree of robustness than earlier biclustering applications. Significance: The use of such approaches is important to investigate the underlying biological substrates of mental illness by grouping patients into homogeneous subjects, as the schizophrenia diagnosis is known to be relatively nonspecific and heterogeneous.
Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of ...published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1-05, 95% CI 1.00-1.11; ORNCC 1-04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I² = 58%, p = 0.002; ORNCC 1-05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing dataseis with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
Background: Few risk factors for childhood cancer are well-established. We investigated whether advancing parental age increases childhood cancer risk. Methods: We assessed the relationship between ...parental age and childhood cancer in a case-control study using pooled population-based data. Our pooling was based on linked cancer and birth registry records from New York, Washington, Minnesota, Texas, and California. Subjects included 17,672 cancer cases diagnosed at ages 0–14 years during 1980–2004 and 57,966 controls born during 1970–2004. Individuals with Down syndrome were excluded. Odds ratios and 95% confidence intervals were calculated by logistic regression for the association between parental age and childhood cancer after adjustment for sex, birth weight, gestational age, birth order, plurality, maternal race, birth year, and state. Results: Positive linear trends per 5-year maternal age increase were observed for childhood cancers overall (odds ratio = 1.08 95% confidence interval = 1.06–1.10) and 7 of the 10 most frequent diagnostic groups: leukemia (1.08 1.05–1.11), lymphoma (1.06 1.01–1.12), central nervous system tumors (1.07 1.03–1.10), neuroblastoma (1.09 1.04–1.15), Wilms' tumor (1.16 1.09–1.22), bone tumors (1.10 1.00–1.20), and soft tissue sarcomas (1.10 1.04–1.17). No maternal age effect was noted for retinoblastoma, germ cell tumors, or hepatoblastoma. Paternal age was not independently associated with most childhood cancers after adjustment for maternal age. Conclusions: Our results suggest that older maternal age increases risk for most common childhood cancers. Investigation into possible mechanisms for this association is warranted.
The challenges of appropriate drug dosing in patients with renal failure requiring renal replacement therapy (RRT) have been exacerbated by recent trends in both RRT technology and practices. Nearly ...all these changes have resulted in augmented drug clearance, making most existing RRT drug dosing recommendations obsolete. Many barriers exist to conducting research to update our knowledge of appropriate drug dosing in the context of contemporary RRT. Recommendations on how this research could be conducted, including the use of in vitro techniques, are offered here.
Clinical Pharmacology & Therapeutics (2009) 86 5, 479–482. doi:10.1038/clpt.2009.150
Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. ...In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.
Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed.
A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio OR: 1.49, 95% confidence interval CI: 1.03–2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05–1.71) and 25% in boys aged 0–14 years (OR: 1.25, 95% CI: 1.06–1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15–2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00–1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers.
Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.
•Accelerated foetal growth was associated with childhood acute myeloid leukaemia.•The association was marked in large-for-gestational-age newborns.•The association was stronger in infant boys and minimally differentiated leukaemia.•Accelerated foetal growth age-, sex- and subtype- related differentials were showed.•These associations could shed light into the biology of AML and its subtypes.
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.
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