High parental occupational social contact and risk of childhood hematopoietic,brain and bone cancers

BackgroundThe etiology of childhood cancer is largely unknown, though some research suggests an infectious origin of hematopoietic, central nervous system (CNS) and bone cancers.MethodsWe examined parental occupational social contact as a proxy for exposure to infectious agents and risk of childhood cancer. This population-based case-control study utilized a linkage of four Danish data-registries, and included 3581 cases (<17 years, diagnosed 1973–2012) and 358,100 age-matched controls. We examined the risks of leukemia, lymphoma, CNS and bone cancer related to high occupational social contact from (1) conception to birth and (2) birth to diagnosis.ResultsAcute lymphoblastic leukemia (ALL) and bone cancer were inversely associated with high maternal social contact from conception to birth (OR: 0.86, 95% CI: 0.67–1.10) and birth to diagnosis (OR: 0.54, 95% CI: 0.34–0.86). Children of fathers with high social contact from birth to diagnosis had an increased risk of bone cancers, particularly in rural areas (OR: 1.65, 95% CI: 1.03–2.63). Parental social contact was associated with increased risk of astrocytoma, with strongest associations found in first-born children (maternal: OR: 1.54, 95% CI: 1.02–2.32; paternal: OR: 1.82, 95% CI: 1.05–3.17).ConclusionOur results support the notion of a role of infections for some cancer types.     

Associations of demographic and perinatal factors with childhood neuroblastoma in Texas, 1995–2011

BackgroundNeuroblastoma, the most common extracranial solid tumor in children, contributes disproportionately to childhood cancer mortality and few risk factors have been identified. Our objective was to evaluate associations between parental and infant characteristics and neuroblastoma incidence.MethodsChildren born in Texas between January 1995 and December 2011 were eligible for the present study. Cases (N = 637) were diagnosed with neuroblastoma in Texas during the same period; controls (N = 6370) matched on year of birth were randomly selected from birth certificates that did not link to a record in the Texas Cancer Registry. We obtained data on birth and parental demographic/reproductive characteristics from birth certificates, and estimated odds ratios (OR) and 95% confidence intervals (CIs) for neuroblastoma using logistic regression.ResultsGestational age 34–36 weeks at birth was associated with neuroblastoma (OR 1.45, CI 1.09–1.90), whereas female sex was inversely associated (OR 0.68, CI 0.58–0.81). Relative to children of non-Hispanic White women, children of Hispanic (OR 0.53, CI 0.43–0.64) or non-Hispanic Black (OR 0.52, CI 0.38–0.71) women were at reduced odds of neuroblastoma. When maternal and paternal race/ethnicity were evaluated jointly, similar patterns were observed (two non-Hispanic Black parents: OR 0.55, 95%CI 0.36–0.79; two Hispanic parents: OR 0.53, 95%CI 0.41–0.67). Older maternal age was also positively associated with neuroblastoma (OR 1.41, CI 1.04–1.90 for 35–39 years; OR 1.62, CI 0.87–2.81 for ≥40 years, relative to 25–29 years).ConclusionsFindings provide further evidence of racial/ethnic disparities in neuroblastoma incidence, determinants of which are unknown. In contrast to most published studies, we observed an association between maternal age and neuroblastoma. Further studies with more robust control for confounding are warranted.     

Predicting the Outcome of Sjogren’s Syndrome-Associated Non-Hodgkin’s Lymphoma Patients

BackgroundNon-Hodgkin''s lymphoma (NHL) development in Sjögren’s syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions.MethodsIn order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated.ResultsMALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14–95.80%) and the EFS was 77.92% (95% CI: 67.37–85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034–26.568) or for event (OR = 4.317, 95% CI: 1.146–9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772–11.637) and OS (HR = 5.946, 95% CI: 1.259–28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656–72.387 and OR = 12.589, 95% CI: 3.911–40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477–21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414–53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes.ConclusionsAt the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.     

Postnatal Environmental Tobacco Smoke Exposure Related to Behavioral Problems in Children

ObjectiveThe purpose of this study was to examine the association between pre and post environmental tobacco smoke (ETS) exposure and behavioral problems in schoolchildren.MethodsIn the cross-sectional 6 cities Study conducted in France, 5221 primary school children were investigated. Pre- and postnatal exposure to secondhand tobacco smoke at home was assessed using a parent questionnaire. Child’s behavioral outcomes (emotional symptoms and conduct problems) were evaluated by the Strengths and Difficulties Questionnaire (SDQ) completed by the parents.ResultsETS exposure during the postnatal period and during both pre- and postnatal periods was associated with behavioral problems in children. Abnormal emotional symptoms (internalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.72 (95% Confidence Interval (CI)= 1.36-2.17), whereas the OR was estimated to be 1.38 (95% CI= 1.12-1.69) in the case of postnatal exposure only. Abnormal conduct problems (externalizing problems) were related to ETS exposure in children who were exposed during the pre- and postnatal periods with an OR of 1.94 (95% CI= 1.51-2.50), whereas the OR was estimated to be 1.47 (95% CI=1.17-1.84) in the case of postnatal exposure only. Effect estimates were adjusted for gender, study center, ethnic origin, child age, low parental education, current physician diagnosed asthma, siblings, preterm birth and single parenthood.ConclusionPostnatal ETS exposure, alone or in association with prenatal exposure, increases the risk of behavioral problems in school-age children.     

Low serum creatinine is associated with type 2 diabetes in morbidly obese women and men: a cross-sectional study

Background

Iodine deficiency is a global problem representing the most common preventable cause of mental retardation. Recently, the impact of subtle deficiencies in iodine intake on children and pregnant women has been questioned. This study was designed to compare hypothyroidism among infants born to US military families in countries of varied iodine nutrition status.

Methods

A cohort design was used to analyze data from the Department of Defense Birth and Infant Health Registry for infants born in 2000-04 (n = 447,691). Hypothyroidism was defined using ICD-9-CM codes from the first year of life (n = 698). The impact of birth location on hypothyroidism was assessed by comparing rates in Germany, Japan, and US territories with the United States, while controlling for infant gender, plurality, gestational age, maternal age, maternal military status, and military parent's race/ethnicity.

Results

Hypothyroidism did not vary by birth location with adjusted odds ratios (OR) as follows: Germany (OR 0.82, [95% CI 0.50, 1.35]), Japan (OR 0.67, [95% CI 0.37, 1.22]), and US territories (OR 1.29, [95% CI 0.57, 2.89]). Hypothyroidism was strongly associated with preterm birth (OR 5.44, [95% CI 4.60, 6.42]). Hypothyroidism was also increased among infants with civilian mothers (OR 1.24, [95% CI 1.00, 1.54]), and older mothers, especially ages 40 years and older (OR 2.09, [95% CI 1.33, 3.30]).

Conclusions

In this study, hypothyroidism in military-dependent infants did not vary by birth location, but was associated with other risk factors, including preterm birth, civilian maternal status, and advanced maternal age.     

Genetic Ancestry and Asthma and Rhinitis Occurrence in Hispanic Children: Findings from the Southern California Children’s Health Study

BackgroundAsthma and rhinitis are common childhood health conditions. Being an understudied and rapidly growing population in the US, Hispanic children have a varying risk for these conditions that may result from sociocultural (including acculturative factors), exposure and genetic diversities. Hispanic populations have varying contributions from European, Amerindian and African ancestries. While previous literature separately reported associations between genetic ancestry and acculturation factors with asthma, whether Amerindian ancestry and acculturative factors have independent associations with development of early-life asthma and rhinitis in Hispanic children remains unknown. We hypothesized that genetic ancestry is an important determinant of early-life asthma and rhinitis occurrence in Hispanic children independent of sociodemographic, acculturation and environmental factors.MethodsSubjects were Hispanic children (5–7 years) who participated in the southern California Children’s Health Study. Data from birth certificates and questionnaire provided information on acculturation, sociodemographic and environmental factors. Genetic ancestries (Amerindian, European, African and Asian) were estimated based on 233 ancestry informative markers. Asthma was defined by parental report of doctor-diagnosed asthma. Rhinitis was defined by parental report of a history of chronic sneezing or runny or blocked nose without a cold or flu. Sample sizes were 1,719 and 1,788 for investigating the role of genetic ancestry on asthma and rhinitis, respectively.ResultsChildren had major contributions from Amerindian and European ancestries. After accounting for potential confounders, per 25% increase in Amerindian ancestry was associated with 17.6% (95% confidence interval [CI]: 0.74–0.99) and 13.6% (95% CI: 0.79–0.98) lower odds of asthma and rhinitis, respectively. Acculturation was not associated with either outcome.ConclusionsEarlier work documented that Hispanic children with significant contribution from African ancestry are at increased asthma risk; however, in Hispanic children who have little contribution from African ancestry, Amerindian ancestry was independently associated with lower odds for development of early-childhood asthma and rhinitis.     

Are there ethnic disparities in risk of preterm birth among infants born with congenital heart defects?

BACKGROUND: Birth defects and preterm birth (PTB) are leading causes of infant morbidity and mortality in the United States. Infants with birth defects are more likely to be born preterm (<37 weeks), yet the roles of maternal ethnicity and fetal growth in this relationship are unclear. This study aimed to assess the risk of PTB among non-Hispanic (NH) Black, NH-White, and Hispanic infants with congenital heart defects (CHD), adjusting for fetal growth. METHODS: Florida Birth Defects Registry data were used to conduct a retrospective cohort study on 14,319 live-born infants with CHDs born January 1, 1998 to December 31, 2002. ORs and 95% CIs were computed for each growth category (small-for-gestational age [SGA], appropriate-for-gestational-age [AGA], and large-for-gestational-age [LGA]) by ethnicity and adjusted for maternal and infant covariates using logistic regression. RESULTS: After adjusting for potential confounders, SGA and AGA NH-Black infants with CHDs had increased risk of PTB compared to NH-White infants with CHDs (OR 1.79; 95% CI: 1.40, 2.30 and OR 1.89; 95% CI: 1.68, 2.13, respectively). Hispanic SGA, AGA, and infants with CHDs had no increased risk of PTB compared to NH-White infants. CONCLUSIONS: The increased risk of PTB among SGA and AGA NH-Black infants with CHDs is not explained by the overall disparities in risk of PTB between NH-Blacks and NH-Whites. Additional studies are needed to determine the specific subtypes of CHD for which these relationships are present and if these findings are seen among infants with other birth defects.     

Developmental trajectories of overweight during childhood: role of early life factors

Objective: Our goal was to identify developmental trajectories of overweight in children and to assess early life influences on these trajectories. Research Methods and Procedures: Participants consisted of 1739 white, black, and Hispanic children who were younger than 2 years at the first survey and were followed up to 12 years of age. Repeated measures of overweight, defined as BMI ≥95th percentile, were used to identify overweight trajectories with a latent growth mixture modeling approach. Results: Three distinct overweight trajectories were identified: 1) early onset overweight (10.9%), 2) late onset overweight (5.2%), and 3) never overweight (83.9%). After adjustment for multiple potential risk factors, male gender [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.0 to 2.2], black ethnicity (OR, 1.7; 95% CI, 1.1 to 2.6), maternal 25 ≤ BMI <30 kg/m² (OR, 2.2; 95% CI, 1.3 to 3.7) or ≥30 kg/m² (OR, 5.1; 95% CI, 2.9 to 9.1), maternal weight gain during pregnancy ≥20.43 kg (OR, 1.7; 95% CI, 1.0 to 2.9), and birth weight ≥4000 g (OR, 2.0; 95% CI, 1.2 to 3.4) were associated with an increased risk of early onset overweight. These risk factors, except maternal weight gain, exerted similar effects on late onset overweight. In addition, maternal smoking (OR, 1.6; 95% CI, 0.8 to 3.1) and birth order ≥3 (OR, 2.3; 95% CI, 1.0 to 5.2) were associated with an increased risk of late onset overweight only. Breastfeeding ≥4 months was associated with a decreased risk of both early (OR, 0.7; 95% CI, 0.3 to 1.3) and late onset overweight (OR, 0.7; 95% CI, 0.3 to 1.7). Discussion: Two trajectories of overweight and one never overweight group were identified. Early life predictors may have a significant influence on the developmental trajectories of overweight in children.     

CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis

CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4⁺ and CD8⁺ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08–1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25–1.66; p = 3.1 × 10^?7), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01–1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02–1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47–0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.     

Association of Germline CHEK2 Gene Variants with Risk and Prognosis of Non-Hodgkin Lymphoma

The checkpoint kinase 2 gene (CHEK2) codes for the CHK2 protein, an important mediator of the DNA damage response pathway. The CHEK2 gene has been recognized as a multi-cancer susceptibility gene; however, its role in non-Hodgkin lymphoma (NHL) remains unclear. We performed mutation analysis of the entire CHEK2 coding sequence in 340 NHL patients using denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation-dependent probe amplification (MLPA). Identified hereditary variants were genotyped in 445 non-cancer controls. The influence of CHEK2 variants on disease risk was statistically evaluated. Identified CHEK2 germline variants included four truncating mutations (found in five patients and no control; P = 0.02) and nine missense variants (found in 21 patients and 12 controls; P = 0.02). Carriers of non-synonymous variants had an increased risk of NHL development [odds ratio (OR) 2.86; 95% confidence interval (CI) 1.42–5.79] and an unfavorable prognosis [hazard ratio (HR) of progression-free survival (PFS) 2.1; 95% CI 1.12–4.05]. In contrast, the most frequent intronic variant c.319+43dupA (identified in 22% of patients and 31% of controls) was associated with a decreased NHL risk (OR = 0.62; 95% CI 0.45–0.86), but its positive prognostic effect was limited to NHL patients with diffuse large B-cell lymphoma (DLBCL) treated by conventional chemotherapy without rituximab (HR-PFS 0.4; 94% CI 0.17–0.74). Our results show that germ-line CHEK2 mutations affecting protein coding sequence confer a moderately-increased risk of NHL, they are associated with an unfavorable NHL prognosis, and they may represent a valuable predictive biomarker for patients with DLBCL.     

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma among women in Connecticut

Several hereditary syndromes characterized by defective DNA repair are associated with high risk of non-Hodgkin lymphoma (NHL). To explore whether common polymorphisms in DNA repair genes affect risk of NHL in the general population, we evaluated the association between single nucleotide polymorphisms (SNPs) in DNA repair genes and risk of NHL in a population-based case–control study among women in Connecticut. A total of 518 NHL cases and 597 controls recruited into the study provided a biologic sample. Thirty-two SNPs in 18 genes involved in several DNA repair pathways were genotyped. Genotype data were analyzed by unconditional logistic regression adjusting for age and race. SNPs in four genes (ERCC5, ERCC2, WRN, and BRCA1) were associated with altered risk of NHL and diffuse large B-cell lymphoma (DLBCL), the major B cell subtype. In particular, ERCC5 Asp1104His was associated with increased risk of NHL overall (OR: 1.46; 95% CI: 1.13–1.88; P = 0.004), DLBCL (OR: 1.44; 95% CI: 0.99–2.09; P = 0.058), and also T cell lymphoma. WRN Cys1367Arg was associated with decreased risk of NHL overall (OR: 0.71; 95% CI: 0.56–0.91; P = 0.007) and DLBCL (OR: 0.66; 95% CI: 0.45–0.95; P = 0.024), as well as follicular and marginal zone lymphomas. Genetic polymorphisms in DNA repair genes, particularly ERCC5 and WRN, may play a role in the pathogenesis of NHL, especially for DLBCL. Further work is needed to extend these findings by carrying out extended haplotype analyses of these and related genes and to replicate the observations in other studies.     

Case-control study of birth characteristics and the risk of hepatoblastoma

Background: Hepatoblastoma is a malignant embryonal tumor typically diagnosed in children younger than five years of age. Little is known on hepatoblastoma etiology. Methods: We matched California Cancer Registry records of hepatoblastomas diagnosed in children younger than age 6 from 1988 to 2007 to birth records using a probabilistic record linkage program, yielding 261 cases. Controls (n = 218,277), frequency matched by birth year to all cancer cases in California for the same time period, were randomly selected from California birth records. We examined demographic and socioeconomic information, birth characteristics, pregnancy history, complications in pregnancy, labor and delivery, and abnormal conditions and clinical procedures relating to the newborn, with study data taken from birth certificates. Results: We observed increased risks for hepatoblastoma among children with low [1500–2499 g, Odds Ratio (OR) = 2.02, 95% confidence interval (CI) 1.29–3.15] and very low birthweight (<1500 g, OR = 15.4, 95% CI 10.7–22.3), preterm birth <33 weeks (OR = 7.27, 95% CI 5.00, 10.6), small size for gestational age (OR = 1.75, 95% CI 1.25–2.45), and with multiple birth pregnancies (OR = 2.52, 95% CI 1.54–4.14). We observed a number of pregnancy and labor complications to be related to hepatoblastoma, including preeclampsia, premature labor, fetal distress, and congenital anomalies. Conclusion: These findings confirm previously reported associations with low birthweight and preeclampsia. The relation with multiple birth pregnancies has been previously reported and may indicate a relation to infertility treatments.     

Photodynamic therapy and tumor imaging of hypericin-treated squamous cell carcinoma

Background

The use of cellular and cordless telephones has increased dramatically during the last decade. There is concern of health problems such as malignant diseases due to microwave exposure during the use of these devices. The brain is the main target organ.

Methods

Since the second part of the 1990's we have performed six case-control studies on this topic encompassing use of both cellular and cordless phones as well as other exposures. Three of the studies concerned brain tumours, one salivary gland tumours, one non-Hodgkin lymphoma (NHL) and one testicular cancer. Exposure was assessed by self-administered questionnaires.

Results

Regarding acoustic neuroma analogue cellular phones yielded odds ratio (OR) = 2.9, 95 % confidence interval (CI) = 2.0–4.3, digital cellular phones OR = 1.5, 95 % CI = 1.1–2.1 and cordless phones OR = 1.5, 95 % CI = 1.04–2.0. The corresponding results were for astrocytoma grade III-IV OR = 1.7, 95 % CI = 1.3–2.3; OR = 1.5, 95 % CI = 1.2–1.9 and OR = 1.5, 95 % CI = 1.1–1.9, respectively. The ORs increased with latency period with highest estimates using > 10 years time period from first use of these phone types. Lower ORs were calculated for astrocytoma grade I-II. No association was found with salivary gland tumours, NHL or testicular cancer although an association with NHL of T-cell type could not be ruled out.

Conclusion

We found for all studied phone types an increased risk for brain tumours, mainly acoustic neuroma and malignant brain tumours. OR increased with latency period, especially for astrocytoma grade III-IV. No consistent pattern of an increased risk was found for salivary gland tumours, NHL, or testicular cancer.     

Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis

Background

Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.

Methods and Findings

Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations. We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%.Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding.

Conclusions

There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.

Review Registration

PROSPERO CRD42013004965 Please see later in the article for the Editors'' Summary     

Cyclin D1 splice variant and risk for non-Hodgkin lymphoma

To investigate the role of cell cycle gene variations in lymphomagenesis, we evaluated associations (odds ratios [OR] and 95% confidence intervals [CI]) in polymorphisms from seven candidate genes in 1,172 non-Hodgkin lymphoma (NHL) cases and 982 population-based controls. The cyclin D1 (CCND1) splice variant G870A (rs603965) increased NHL risk (OR_AA = 1.4, 95% CI = 1.1–1.8, P-trend = 0.021), which was consistent for four B-cell subtypes. As CCND1 expression indicates poor NHL prognosis, our results, if true, would support its potentially dual importance in NHL etiology and survival.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .     

Separating parental and treatment contributions to perinatal health after fresh and frozen embryo transfer in assisted reproduction: A cohort study with within-sibship analysis

BackgroundCompared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors.Methods and findingsThis registry-based cohort study with nationwide data from Denmark (1994–2014), Norway (1988–2015), and Sweden (1988–2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (<37 weeks, versus ≥37), and very preterm birth (<32 weeks, versus ≥32). Singletons born after fresh-ET had lower mean birthweight (−51 g, 95% CI −58 to −45, p < 0.001) and increased odds of small for gestational age (odds ratio [OR] 1.20, 95% CI 1.08 to 1.34, p < 0.001), while those born after frozen-ET had higher mean birthweight (82 g, 95% CI 70 to 94, p < 0.001) and increased odds of large for gestational age (OR 1.84, 95% CI 1.56 to 2.17, p < 0.001), compared to naturally conceived siblings. Conventional population analyses gave similar results. Compared to naturally conceived siblings, mean gestational age was lower after fresh-ET (−1.0 days, 95% CI −1.2 to −0.8, p < 0.001), but not after frozen-ET (0.3 days, 95% CI 0.0 to 0.6, p = 0.028). There were increased odds of preterm birth after fresh-ET (OR 1.27, 95% CI 1.17 to 1.37, p < 0.001), and in most models after frozen-ET, versus naturally conceived siblings, with somewhat stronger associations in population analyses. For very preterm birth, population analyses showed increased odds for both fresh-ET (OR 2.03, 95% CI 1.90 to 2.12, p < 0.001) and frozen-ET (OR 1.66, 95% CI 1.42 to 1.94, p < 0.001) compared with natural conception, but results were notably attenuated within siblings (OR 1.18, 95% CI 1.0 to 1.41, p = 0.059, and OR 0.92, 95% CI 0.67 to 1.27, p = 0.6, for fresh-ET and frozen-ET, respectively). Sensitivity analyses in full siblings, in siblings born within 3-year interval, by birth order, and restricting to single embryo transfers and blastocyst transfers were consistent with the main analyses. Main limitations were high proportions of missing data on maternal body mass index and smoking.ConclusionsWe found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias.Trial registrationClinicalTrials.gov ISRCTN11780826.

Kjersti Westvik-Johari and co-workers report on perinatal outcomes following fresh and frozen embryo transfer.     

The Role of Prenatal Care and Social Risk Factors in the Relationship between Immigrant Status and Neonatal Morbidity: A Retrospective Cohort Study

Background and Aim

Literature evaluating association between neonatal morbidity and immigrant status presents contradictory results. Poorer compliance with prenatal care and greater social risk factors among immigrants could play roles as major confounding variables, thus explaining contradictions. We examined whether prenatal care and social risk factors are confounding variables in the relationship between immigrant status and neonatal morbidity.

Methods

Retrospective cohort study: 231 pregnant African immigrant women were recruited from 2007–2010 in northern Spain. A Spanish population sample was obtained by simple random sampling at 1:3 ratio. Immigrant status (Spanish, Sub-Saharan and Northern African), prenatal care (Kessner Index adequate, intermediate or inadequate), and social risk factors were treated as independent variables. Low birth weight (LBW < 2500 grams) and preterm birth (< 37 weeks) were collected as neonatal morbidity variables. Crude and adjusted odds ratios (OR) were estimated by unconditional logistic regression with 95% confidence intervals (95% CI).

Results

Positive associations between immigrant women and higher risk of neonatal morbidity were obtained. Crude OR for preterm births in Northern Africans with respect to nonimmigrants was 2.28 (95% CI: 1.04–5.00), and crude OR for LBW was 1.77 (95% CI: 0.74–4.22). However, after adjusting for prenatal care and social risk factors, associations became protective: adjusted OR for preterm birth = 0.42 (95% CI: 0.14–1.32); LBW = 0.48 (95% CI: 0.15–1.52). Poor compliance with prenatal care was the main independent risk factor associated with both preterm birth (adjusted OR inadequate care = 17.05; 95% CI: 3.92–74.24) and LBW (adjusted OR inadequate care = 6.25; 95% CI: 1.28–30.46). Social risk was an important independent risk factor associated with LBW (adjusted OR = 5.42; 95% CI: 1.58–18.62).

Conclusions

Prenatal care and social risk factors were major confounding variables in the relationship between immigrant status and neonatal morbidity.     

Occupational exposure to immunologically active agents and risk for lymphoma: The European Epilymph case–control study

ObjectivesAllergies and asthma may be protective for the development of lymphoma. We evaluated whether occupational allergens that provoke immune reactivity and asthma through an IgE-mediated pathway are protective for lymphoma.MethodsThe Epilymph study includes histologically or cytologically confirmed Hodgkin, B-cell, and T-cell lymphoma cases from six European countries (Spain, France, Germany, Italy, Ireland, and Czech Republic) recruited in 1998–2004. Controls were frequency matched to cases by age, gender, and study centre. Lifetime occupational exposure to seven high molecular weight (HMW) agents was evaluated through an asthma-specific job-exposure matrix. 2205 lymphoma cases and 2296 controls with complete occupational history could be included in the analysis. Associations between HMW exposures and lymphoma were evaluated using pooled unconditional logistic regression analyses.ResultsIndividuals exposed to HMW agents had a non-statistically significant decreased risk of any lymphoma (OR, 0.88: 95% CI, 0.74–1.05) and of B-cell lymphoma (OR, 0.91; 95% CI, 0.76–1.09), and a significantly decreased risk for Hodgkin lymphoma (OR, 0.62; 95% CI, 0.40–0.98). A decrease in risk for lymphoma was found for exposure to latex (OR, 0.74; 95% CI, 0.55–0.99).ConclusionsFurther epidemiologic and mechanistic research is needed to confirm that occupational exposure to HMW agents predisposing to asthma can reduce the risk of lymphoma.     

Pre- and Postnatal Risk Factors in Relation to Allergic Rhinitis in School-Aged Children in China

ObjectiveThe objective of this study was to investigate the relationship between prenatal and postnatal risk factors and the prevalence of allergic rhinitis (AR) in Chinese children of specific ages.ResultsThe overall prevalence of AR was found in this study to be 9.8%. After adjusting for several likely confounders, there was a higher likelihood of AR in school-aged children who were not exclusively breastfed in the first 4 months of their lives (odds ratio [OR]: 1.28; 95% confidence interval [CI]: 1.16–1.41), children who were born post-term (OR: 1.34; 95% CI: 1.12–1.60), children delivered by cesarean section (OR: 1.07; 95% CI: 1.00–1.19), or children born to mothers who experienced depressive symptoms during the pre- and postnatal periods (OR: 1.28; 95% CI: 1.15–1.42).ConclusionsAR in school-aged children was found to be associated with pre- and postnatal events. These findings indicate that strategies to reduce exposure to risk factors during pre- and postnatal periods for childhood allergies might be warranted.     

Blood Erythrocyte Concentrations of Cadmium and Lead and the Risk of B-Cell Non-Hodgkin’s Lymphoma and Multiple Myeloma: A Nested Case-Control Study

Background

Cadmium (Cd) and lead (Pb) are hypothesised to be risk factors for non-Hodgkin’s lymphoma (NHL), a group of haematological malignancies with a suspected environmental aetiology. Within the EnviroGenoMarkers study we utilised pre-diagnostic erythrocyte concentrations of Cd and Pb to determine whether exposure was associated with risk of B-cell NHL and multiple myeloma.

Methods

194 incident cases of B-cell NHL and 76 cases of multiple myeloma diagnosed between 1990 and 2006 were identified from two existing cohorts; EPIC-Italy and the Northern Sweden Health and Disease Study. Cases were matched to healthy controls by centre, age, gender and date of blood collection. Cd and Pb were measured in blood samples provided at recruitment using inductively coupled plasma-mass spectrometry. Logistic regression was applied to assess the association with risk. Analyses were stratified by cohort and gender and by subtype where possible.

Results

There was little evidence of an increased risk of B-cell NHL or multiple myeloma with exposure to Cd (B-cell NHL: OR 1.09 95%CI 0.61, 1.93, MM: OR 1.16 95% CI: 0.40, 3.40 ) or Pb (B-cell NHL: 0.93 95% CI 0.43, 2.02, multiple myeloma: OR 1.63 95%CI 0.45, 5.94) in the total population when comparing the highest to the lowest quartile of exposure. However, gender and cohort specific differences in results were observed. In females the risk of B-cell NHL was more than doubled in those with a body burden of Cd >1µg/L (OR 2.20 95%CI; 1.04, 4.65).

Conclusions

This nested case-control study does not support a consistent positive association between Cd or Pb and NHL, but there is some indication of a gender specific effect suggesting further research is warranted.