Risk Of Childhood Cancer Research Articles

O-274 Cancer in Children Born after Frozen-Thawed Embryo Transfer: A Cohort Study

Abstract Study question Do children conceived after assisted reproductive technology (ART), particularly after frozen/thawed embryo transfer (FET), have a higher risk of cancer? Summary answer Children born after FET have a higher risk of childhood cancer than children born after fresh embryo transfer and spontaneous conception. What is known already Previous studies on the association of ART conception and risk of childhood cancer show conflicting results. Worldwide, the number of children born after FET increases and in many countries the number of children born after FET now exceeds the number of children born after fresh embryo transfer. Children born after FET are at increased risk of macrosomia which has been associated with a higher risk of childhood cancer. Study design, size, duration This large Nordic registry-based cohort study included 171 774 children born after use of ART and 7 772 474 children born after spontaneous conception during a study period of up to three decades (Denmark 1994-2014, Finland 1990-2014, Norway 1984-2015 and Sweden 1985-2015). Participants/materials, setting, methods Cancer rates in children born after each conception method were determined by cross-linking data from national ART and birth registries, national cancer and population registries. The primary outcome was any cancer, and secondary outcomes were 12 cancer subgroups according to the International Classification of Childhood Cancer (ICCC-3). Children were followed from birth to cancer diagnosis, death, emigration, age 18 years or the end of the study period, whichever came first. Main results and the role of chance Mean follow up was 9.9 years for children born after ART and 12.5 years for children born after spontaneous conception. Incidence rate (IR) of any cancer before 18 years of age was 19.3/100 000 person-years for children born after ART (329 cases) and 16.7/100 000 person-years for children born after spontaneous conception. Adjusted hazard ratio (aHR) was 1.08, 95% confidence interval (CI) 0.96-1.21. Adjustment was performed for sex, plurality, country of birth, year of birth, maternal age at birth, and parity. Children born after FET had a higher risk of any cancer (48 cases, IR 30.1/100 000 person-years), compared to both children born after fresh embryo transfer (227 cases, IR 18.8/100 000 person-years) (aHR 1.59, 95% CI, 1.15 to 2.20) and children born after spontaneous conception (aHR 1.64, 95% CI, 1.24 to 2.19). Adjustment for macrosomia (birthweight </≥4000 g), birthweight (continuous variable) or major birth defects only slightly attenuated the association. For cancer subgroups, higher risks of epithelial tumours and melanoma after any ART and of leukaemia after FET were observed. Limitations, reasons for caution The main limitation is the number of children with cancer in the FET group. Although including a large cohort, the number of children with cancer is of moderate size. Furthermore, all data are observational, and residual confounding by factors as genetics, parental preconception health and lifestyle cannot be excluded. Wider implications of the findings While risk of any cancer was not higher in children born after any ART, we found that children born after FET had a higher risk of cancer than children born after fresh transfer and spontaneously conceived children. These findings are important considering the increasing use of the freeze-all strategy. Trial registration number ISRCTN11789826

Molecular Basis of Beckwith-Wiedemann Syndrome Spectrum with Associated Tumors and Consequences for Clinical Practice.

Simple SummaryBeckwith–Wiedemann syndrome (BWS, OMIM 130650) is an inborn overgrowth disorder caused by molecular alterations in chromosome 11p15.5. These molecular changes affect so-called imprinted genes, i.e., genes which underlie a complex regulation which is linked to the parental origin of the gene copy. Thus, either the maternal gene copy is expressed or the paternal, but this balanced regulation is prone to disturbances. In fact, different types of molecular variants have been identified in BWS, resulting in a variable phenotype; thus, it was consented that the syndromic entity was extended to the Beckwith–Wiedemann spectrum (BWSp). Some molecular subgroups of BWSp are associated with an increased embryonic tumor risk and have different likelihoods for specific tumors. Therefore, the precise determination of the molecular subgroup is needed for precise monitoring and treatment, but the molecular diagnostic procedure has several limitations and challenges which have to be considered.Beckwith–Wiedemann syndrome (BWS, OMIM 130650) is a congenital imprinting condition with a heterogenous clinical presentation of overgrowth and an increased childhood cancer risk (mainly nephroblastoma, hepatoblastoma or neuroblastoma). Due to the varying clinical presentation encompassing classical, clinical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly, the syndromic entity was extended to the Beckwith–Wiedemann spectrum (BWSp). The tumor risk of up to 30% depends on the molecular subtype of BWSp with causative genetic or epigenetic alterations in the chromosomal region 11p15.5. The molecular diagnosis of BWSp can be challenging for several reasons, including the range of causative molecular mechanisms which are frequently mosaic. The molecular basis of tumor formation appears to relate to stalled cellular differentiation in certain organs that predisposes persisting embryonic cells to accumulate additional molecular defects, which then results in a range of embryonal tumors. The molecular subtype of BWSp not only influences the overall risk of neoplasia, but also the likelihood of specific embryonal tumors.

Is neonatal phototherapy associated with a greater risk of childhood cancers?

BackgroundNeonatal phototherapy (NNPT) has long been used as an effective and relatively safe method of treating neonatal hyperbilirubinemia. Considering the subsequent evidence of long-term impacts of NNPT such as malignancies, this study was conducted to evaluate the relationship between NNPT and childhood cancers.MethodsThis case-control study assessed 116 children up to 4 years old with every kind of cancer referred to the Oncology department of Afzalipour hospital, Kerman, Iran, from 2011 to 18. Moreover, 116 pediatric patients without cancer hospitalized at the same Center were included after sex and age matching as the control group. The history of phototherapy and its duration were evaluated in these two groups.ResultsWe found no association between the NNPT and malignancies in children. However, high intensive phototherapy was higher historically among affected cancerous patients than in non-cancerous cases without any statistically significant difference (25% vs 19%; P = 0.26). Maternal educational level and history of maternal infection during pregnancy, which initially appeared to be two factors associated with malignancy in single variable regression analyses, were not significant based on the adjusted models.ConclusionsThe results did not show a positive correlation between NNPT and childhood cancers, which may partly be due to the relatively small sample size of the study. However, some other evidence is worrisome enough that NNPT should not be considered risk-free. Additional multi-centric studies should be undertaken to specify that phototherapy is really safe.

Residential road traffic and railway noise and risk of childhood cancer: A nationwide register-based case-control study in Denmark

BackgroundThe aetiology of most childhood cancers remains poorly understood. We conducted a nationwide register-based case-control study to assess the association between residential road traffic and railway noise exposure and risk of childhood cancers. MethodsWe identified all cases of first cancers diagnosed in children aged 0–19 years in 1985–2013 from the Danish Cancer Registry (N = 3962) and sampled four individually matched (by sex and date of birth) controls per case (N = 14,790) using the Central Population Register. We estimated time-weighted exposure averages of residential road traffic and railway noise at the most (Lden max) and least (Lden min) exposed façades from birth to index-date (for additional analysis: in utero period) based on the individual address history for the respective time windows. We fitted conditional logistic regression models to estimate odds ratios (OR) and their 95% confidence intervals (CI). ResultsORs varied by noise estimate and cancer type, with generally wide CIs mostly including 1.00. We found a tendency of higher ORs with increasing railway and road traffic noise for Hodgkin lymphoma (ORs for railway and road Lden min were 1.63 (95% CI 1.00; 2.66) and 1.14 (95% CI 0.87; 1.48) per 10 dB), as well as a tendency of higher ORs with increasing railway noise for non-Hodgkin lymphoma. For embryonal CNS tumours and astrocytoma and other glioma we observed also some weak suggestions of a positive association. Analysing exposure to traffic noise in utero revealed similar patterns to those of the main analyses. ConclusionsThis nationwide study with minimal risk of bias suggests no strong associations between traffic noise and risk of most childhood cancers. We found however some suggestive evidence for a positive association with Hodgkin lymphoma, non-Hodgkin lymphoma and some CNS tumours. Further research is warranted to confirm these associations in other populations and elucidate the underlying biological mechanisms.

Association between caesarean birth and childhood cancer: An age-lagged approach.

We assessed the association between caesarean birth and age-specific risks of childhood cancer. We followed a cohort of 1034049 children between 2006 and 2020 in Quebec, Canada, from birth until age 14years. The exposure was caesarean, operative vaginal, or spontaneous vaginal birth. The outcome included haematopoietic or solid tumours. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between mode of delivery and childhood cancer in age-lagged analyses, adjusted for potential confounders. A total of 249415 (24.1%) children were born by caesarean and 97411 (9.4%) by operative vaginal delivery. Compared with spontaneous vaginal birth, caesarean was associated with 1.16 times the risk of any cancer (95% CI 1.04-1.30), 1.12 times the risk of haematopoietic cancer (95% CI 0.92-1.36) and 1.21 times the risk of solid tumours (95% 1.06-1.39). Associations strengthened at 2years of age and were greatest for lymphoma and sarcoma. Operative vaginal birth was not significantly associated with the risk of cancer. Caesarean birth may be associated with selected childhood cancers, including lymphoma and sarcoma early in childhood. The underlying reasons for the associations require further investigation, including whether mucosal dysbiosis or labour hormone exposure explain the excess risk.

Childhood cancer risks estimates following CT scans: an update of the French CT cohort study.

Increased risks of central nervous system (CNS) tumors and leukemia associated with computed tomography (CT) exposure during childhood have been reported in recent epidemiological studies. However, no evidence of increased risks was suggested in a previous analysis of the French CT cohort. This study benefits from an updated cohort with a longer follow-up and a larger sample size of patients. The patients were followed from the date of their first CT (between 2000 and 2011) until their date of cohort exit defined as the earliest among the following: 31 December 2016, date of death, date of first cancer diagnosis or date of their 18th birthday. Cancer incidence, vital status, cancer predisposing factors (PFs), and additional CT scans were collected via external national databases. Hazard ratios (HRs) associated to cumulative organ doses and sex were estimated from Cox models. At the end of follow-up, mean cumulative doses were 27.7 and 10.3 mGy for the brain and the red bone marrow (RBM), respectively. In patients without PFs, an HR per 10 mGy of 1.05 (95% CI: 1.01-1.09) for CNS tumors, 1.17 (95% CI: 1.09-1.26) for leukemia, and 0.96 (95% CI: 0.63-1.45) for lymphoma was estimated. These estimates were not modified by the inclusion of CT scans performed outside the participating hospitals or after the inclusion period. This study shows statistically significant dose-response relationships for CNS tumors and leukemia for patients without PFs. • Computed tomography is the most important contributor to the collective dose for diagnostic imaging to the French population. • Concerns have been raised about possible cancer risks, particularly after exposure to CT in childhood, due to the greater radiation sensitivity of children and to their longer life expectancy. • Analysis of the updated French CT cohort shows statistically significant dose-response relationships for CNS tumors and leukemia.

The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study.

Birth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children. All individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population-based cohort study (n = 4,178,722). Individuals with CHD (n = 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (<20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes. We found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.

Quantifying cancer risk from exposures to medical imaging in the Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study: research methods and cohort profile.

The Risk of Pediatric and Adolescent Cancer Associated with Medical Imaging (RIC) Study is quantifying the association between cumulative radiation exposure from fetal and/or childhood medical imaging and subsequent cancer risk. This manuscript describes the study cohorts and research methods. The RIC Study is a longitudinal study of children in two retrospective cohorts from 6 U.S. healthcare systems and from Ontario, Canada over the period 1995-2017. The fetal-exposure cohort includes children whose mothers were enrolled in the healthcare system during their entire pregnancy and followed to age 20. The childhood-exposure cohort includes children born into the system and followed while continuously enrolled. Imaging utilization was determined using administrative data. Computed tomography (CT) parameters were collected to estimate individualized patient organ dosimetry. Organ dose libraries for average exposures were constructed for radiography, fluoroscopy, and angiography, while diagnostic radiopharmaceutical biokinetic models were applied to estimate organ doses received in nuclear medicine procedures. Cancers were ascertained from local and state/provincial cancer registry linkages. The fetal-exposure cohort includes 3,474,000 children among whom 6,606 cancers (2394 leukemias) were diagnosed over 37,659,582 person-years; 0.5% had in utero exposure to CT, 4.0% radiography, 0.5% fluoroscopy, 0.04% angiography, 0.2% nuclear medicine. The childhood-exposure cohort includes 3,724,632 children in whom 6,358 cancers (2,372 leukemias) were diagnosed over 36,190,027 person-years; 5.9% were exposed to CT, 61.1% radiography, 6.0% fluoroscopy, 0.4% angiography, 1.5% nuclear medicine. The RIC Study is poised to be the largest study addressing risk of childhood and adolescent cancer associated with ionizing radiation from medical imaging, estimated with individualized patient organ dosimetry.

Childhood cancer risk in offspring of parents occupationally exposed to dusts: A register-based nested case-control study from Sweden of 5 decades.

BackgroundSome largely inconsistent associations between parental occupational dust exposure and childhood cancer have been reported, with maternal exposures inadequately studied. The authors examined whether maternal or paternal occupational exposure to animal, wood, textile, or paper dust around a child's birth was associated with an increased risk of childhood cancer, both overall and by type (leukemias, lymphomas, central nervous system tumors, and other cancers).MethodsIn this nationwide, register‐based, case‐control study, children who were diagnosed with cancer from 1960 to 2015 were compared with up to 25 matched controls regarding maternal and paternal occupational dust exposure (9653 cases in maternal analyses and 12,521 cases in paternal analyses). Exposures were assessed using a job‐exposure matrix and occupational information from census and register data. By using conditional logistic regression models, adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated.ResultsNeither maternal nor paternal occupational exposure to animal, wood, textile, or paper dust was associated with childhood cancer overall, leukemias, or central nervous system tumors. Maternal, but not paternal, wood dust exposure was associated with an increased risk of lymphoma (OR, 1.42; 95% CI, 1.10‐1.84), particularly non‐Hodgkin lymphoma (OR, 2.03; 95% CI, 1.21‐3.40).ConclusionsThe current study did not confirm the associations reported previously but is the first to suggest a link between maternal occupational exposure to wood dust around pregnancy and lymphoma in the offspring.

Evaluation of the Fetal-Maternal Radiation Doses in CT-Pelvimetry and Estimation of the Fetal Radiation Risks in 03 Radiology Departments in Douala-Cameroon

Background: CT in pregnant patients requires careful consideration of the radiation dose and corresponding radiation risks from ionizing radiation to the unborn child. The determination of foetal dose in diagnostic radiology is of interest as a basis for risk estimates from medical exposure of the pregnant patient. Objective: To evaluate the foetal-maternal radiation doses delivered during the CT-Pelvimetry procedure and to estimate the risk to the unborn child to develop a cancer in childhood and hereditary disease. Materials and Methods: We investigate the foetal-maternal radiation doses during CT-scan Pelvimetry in Douala (Cameroon). Data of 194 helical acquisition CT-Pelvimetry were collected between May 2017 and May 2019. An average DLP for the examination was established and the average effective dose was evaluated. The fetal dose was calculated and the FetDose V5 program was used for risk estimations. Results: The average dose length product (DLP) was 56.17 mGy·cm (range: 51.69 - 59.21 mGy·cm). The average effective dose received by women pregnant was 0.78 mSv. The mean individual fetal dose was 1.5 mGy (range: 0.76 - 1.87 mGy). The risk of Childhood Cancer calculated was: range 1 in 16,000 to 1 in 10,000 and 1 in 260,000 to 1 in 106,000 to the risk of Hereditary Disease, respectively. Conclusion: This study shows that the foetal-maternal doses delivered during CT-Pelvimetry examinations are very low and the risks of childhood cancers and hereditary diseases are derisory, the technology should be further investigated to ensure its full potential for optimal diagnostic accuracy.

Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring.

Simple SummaryMaternal thyroid disease, especially hypothyroidism, is known to affect pregnancy and its outcome. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. In our study, maternal hypothyroidism was associated with an increased risk of lymphoma in the offspring. The association remained stable when possible familial cancers were excluded.Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00–2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29–10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers.

Childhood cancer and residential proximity to petrol stations: a nationwide registry-based case–control study in Switzerland and an updated meta-analysis

PurposeBenzene is a known carcinogen for adult leukemia. Exposure to benzene through parental occupation and the use of household products has been associated with childhood leukemia (CL). Ambient benzene has also been associated with CL and central nervous system (CNS) tumors. We aimed to investigate whether the higher ambient levels of benzene in proximity of petrol stations are associated with a greater risk of childhood cancers, leukemia, and CNS tumors.MethodsWe identified children diagnosed with cancer at age 0–15 years during 1985–2015 from the Swiss Childhood Cancer Registry and selected 10 age and sex-matched controls per case from national censuses. We calculated the distance from children’s home to the nearest petrol station using precise geocodes. We estimated odds ratios using conditional logistic regression adjusting for ambient levels of NO2, distance to highways, level of urbanization, and presence of a cantonal cancer registry. In addition, we ran a meta-analysis pooling current results for CL with those of previous studies.ResultsWe identified 6129 cases, of which 1880 were leukemias and 1290 CNS tumors. 24 cases lived within 50 m from a petrol station. The adjusted odds ratio of a cancer diagnosis for children thus exposed compared to unexposed children (> 500 m) was 1.29 (0.84–1.98) for all cancers combined, 1.08 (0.46–2.51) for leukemia, and 1.30 (0.51–3.35) for CNS tumors. During 2000–2015, when exposure assessment was more precise, the adjusted odds ratio for any cancer diagnosis was 1.77 (1.05–2.98). The summary relative risk estimate for CL in the meta-analysis including four studies was 2.01 (1.25–3.22).ConclusionsOur study provides weak support for an increased risk of childhood cancers among children living close to petrol stations. A meta-analysis including our study suggests an increased risk for CL.

Exposure to Nitrate from Drinking Water and the Risk of Childhood Cancer in Denmark

BACKGROUND AND AIM: There is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in a large population based case control study in Denmark with high quality estimates of individual exposures to nitrate in drinking water.. METHODS: We conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N=1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNS) who were 15 years of age at diagnosis and were identified from the Danish Cancer Registry. Approximately 100 controls were randomly selected and matched to each case on date of birth and sex. Nitrate measurements in public water systems were linked with an address registry to estimate individual average nitrate concentrations during preconception, prenatal, and postnatal periods. Odd ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression controlling for the matching variables, and birth order, birthweight, urbanicity, maternal education, employment, income and smoking, and parental age. RESULTS:There was no evidence of an association of nitrate with leukemia or lymphoma. An association between CNS and the highest category of nitrate exposure (25 mg/L nitrate) was observed for preconception (OR=1.82, 95%CI=1.09 to 3.04), prenatal (OR=1.65, 95%CI=0.97 to 2.81), and postnatal exposure (OR=1.48, 95%CI=0.82 to 2.68) in fully-adjusted models. There was also some evidence of an exposure-response in models of continuous nitrate exposure and CNS. CONCLUSIONS:Our findings provide some evidence that exposure to nitrate from drinking water may increase the risk of childhood CNS cancer, but not leukemia or lymphoma. Exposures in this study were generally well below current European and US maximum allowable concentrations, which in addition to previous studies, raises concerns about the adequacy of these standards for protecting children's health. KEYWORDS: nitrate, drinking water, childhood leukemia, lymphoma and central nervous system cancer

Association between long-term exposure to particulate matter and childhood cancer: Retrospective cohort study

BACKGROUND AND AIM: Particulate matter is known carcinogen, but its association with childhood cancer is inconsistent. The aim of the present study was to examine the association between air pollution and childhood cancer. METHODS: A retrospective cohort was constructed from claims database of the Korea National Health Insurance Service. Children who had been born in 7 metropolitan cities in Korea (Seoul, Incheon, Daejeon, Gwangju, Daegu, Busan, and Ulsan) from 2002 to 2012 were recruited and half of them were randomly selected. Children who were diagnosed with cancer within 5 years of birth were excluded. Monthly mean concentrations of particulate matter with aerodynamic diameter 10 μm (PM10) and other air pollutants (NO2, SO2, CO and O3) was calculated from AirKorea. Monthly mean concentrations of particulate matter with aerodynamic diameter 2.5 μm (PM2.5) was estimated with a concentration prediction model. The cumulative exposure was calculated by averaging monthly concentrations according to the subject's residential information. We constructed Cox proportional hazard model adjusting for potential confounders and O3 concentration. RESULTS:A total of 1,261,855 children (boys 641,704, girls 610,151) were included in the analysis. During the study period, 1,725 were newly diagnosed with cancer. Exposures to higher mean ambient PM2.5 and PM10 concentration increased the risk of childhood cancer. The hazard ratio of all cancers was 3.02 (95% confidence interval [CI]: 1.63, 5.59) and 1.04 (95% CI: 0.71, 1.45) for an increment of 10 μg/m3 of annual mean concentrations of PM2.5 and PM10, respectively. CONCLUSIONS:We observed significant positive association between particulate matter exposure and childhood cancer in a retrospective cohort of 1.2 million children. KEYWORDS: Particulate matter, Cancer, Children, Retrospective cohort

Infantile neuroblastoma and maternal occupational exposure to medical agents.

Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study aimed to examine whether such occupational exposure increased the risk of childhood cancer in offspring. We used the dataset of the Japan Environment and Children's Study, a nationwide birth cohort involving over 100,000 mother-child pairs. Information was obtained via successive questionnaires that were completed until the child turned 1 year of age. The parents were asked whether they occupationally handled medical agents during pregnancy. A total of 26 infants developed neoplasms: neuroblastoma, leukemia, and brain tumor. The incidence of neuroblastoma was significantly higher in infants whose mothers were exposed to radiation (3/2142: 140.1 per 100,000 population) than in those who were not (12/90,384: 13.3 per 100,000 population). Multivariable regression analyses revealed a close association between maternal irradiation and the development of neuroblastoma (adjusted incident rate ratio: 10.68 [95% confidence interval: 2.98‒38.27]). The present study demonstrated, for the first time, a potential association between maternal occupational exposure and the occurrence of neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results. Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study examined the association between such occupational exposure and offspring's cancers that developed until the age of 1 year. Maternal exposure to ionizing radiation was associated with infantile neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results.

Exposure to nitrate from drinking water and the risk of childhood cancer in Denmark

BackgroundThere is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in Denmark. MethodsWe conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N = 1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNC) who were ≤15 years of age at diagnosis and were identified from the Danish Cancer Registry. Approximately 100 controls were randomly selected and matched to each case on date of birth and sex. Nitrate measurements in public water systems were linked with an address registry to estimate individual average nitrate concentrations during preconception, prenatal, and postnatal periods. Odd ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression controlling for the matching variables, and birth order, birthweight, urbanicity, maternal education, employment, income and smoking, and parental age. ResultsThere was no evidence of an association of nitrate with leukemia or lymphoma. An association between CNC and the highest category of nitrate exposure (>25 mg/L nitrate) was observed for preconception (OR = 1.82, 95%CI:1.09 to 3.04), prenatal (OR = 1.65, 95%CI:0.97 to 2.81), and postnatal exposure (OR = 1.48, 95%CI:0.82 to 2.68) in fully adjusted models. There was also some evidence of an exposure–response in models of continuous nitrate exposure and CNC. ConclusionsOur findings provide some evidence that exposure to nitrate from drinking water may increase the risk of childhood CNC cancer, but not leukemia or lymphoma.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Invited Perspective: Air Pollution and Breast Cancer Risk: Current State of the Evidence and Next Steps.

Breastfeeding and the risk of childhood cancer: a systematic review and dose-response meta-analysis

BackgroundThe aim of this study was to quantitatively summarize the available evidence on the association of breastfeeding with the risk of childhood cancer.MethodsA literature search of PubMed and Embase databases was performed to identify eligible observational studies published from inception to July 17, 2020. The categorical and dose-response meta-analysis was conducted by pooling relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs). Potential sources of heterogeneity were detected by meta-regression and stratification analysis. Sensitivity analysis and publication bias test were also carried out.ResultsForty-five articles involving 475,579 individuals were included in the meta-analysis. Among the thirty-three studies on the association between breastfeeding and risk of childhood leukemia, the pooled risk estimates were 0.77 (95% CI, 0.65–0.91) and 0.77 (95% CI 0.63–0.94) for ever versus non/occasional breastfeeding and longest versus shortest breastfeeding duration group, respectively. There was clear indication for non-linear dose-response relationship between breastfeeding duration and the risk of childhood leukemia (P non-linear < 0.001). The most protective effect (OR, 0.66, 95% CI 0.62–0.70) was observed at a breastfeeding duration of 9.6 months. Four studies examined, the association between breastfeeding and risk of childhood neuroblastoma, and significant inverse associations were consistently observed in both the comparisons of ever breastfeeding versus non/occasional breastfeeding (OR = 0.59, 95% CI 0.44–0.81) and longest versus shortest breastfeeding (OR = 0.61, 95% CI 0.44–0.83). However, no associations of breastfeeding with risk of other cancers were found.ConclusionsOur study supports a protective role of breastfeeding on the risk of childhood leukemia, also suggesting a non-linear dose-response relationship. Further studies are warranted to confirm the association between breastfeeding and risk of childhood neuroblastoma.

Assessment of radiation dose to pediatric patients during routine digital chest X-ray procedure in a government medical centre in Asaba, Nigeria

Objective: Radiation dose to pediatric patients have been widely reported, it is however necessary that imaging expert keep doses as low as possible to forestall stall long term cancer risk. This study is aimed at determining pediatric entrance surface dose (ESD), 75th percentile ESD, absorbed dose (D) and effective dose (E) for 0-15 years.&#x0D; Material and Methods: The study used a digital radiography (DR) unit with a grid system for each chest X-ray. The thermoluminescent dosimeter (TLD) used was encapsulated in transparent nylon, it was then attached to the patient skin (chest wall) and the second was placed directly at the posterior end of it.&#x0D; Results: The mean ESDs for the 4 age groups were as follows: 0- &lt; 1 (1.54±0.74mGy), 1- &lt; 5 (1.53±0.83mGy), 5- &lt; 10 (0.55±0.39mGy) and 10- ≤15 (1.30±0.57mGy), with an overall mean of 1.23mGy. The 75th percentile ESD for each age group above 10 patients (excluding 5- &lt; 10yrs) was 2.18, 2.19 and 1.75mGy respectively. The absorbed dose (D) ranged from 0.03-2.39mGy. The mean effective dose (E) for the 4 age groups was 0.18±0.03mSv. There was a good correlation between ESD and D (P = 0.001). A One-Way ANOVA shows that the field size and focus to film distance (FFD) affected the ESD and D (P &lt; 0.001) respectively. The risk of childhood cancer from a single radiograph was of the order of (1.54-23.4) ×10-6.&#x0D; Conclusion: The 75th percentile ESD, E and childhood risk of cancer was higher than most studies it was compared with. The study reveals that machine parameters such as the field size and FFD played a major role in dose increase. Protocol optimization is currently needed for pediatric patients in the studied facility.

Cesarean Section Is Associated with an Increased Risk of Acute Lymphoblastic Leukemia and Hepatoblastoma in Children from Minnesota.

In recent decades, Cesarean section (C-section) rates have increased. C-section is hypothesized to negatively impact the developing immune system by altering activation of the hypothalamic-pituitary-adrenal axis and the infant microbiome, among other mechanisms, thereby potentially modulating childhood cancer risk. Using linked birth and cancer registry data from Minnesota (1976-2014), we included individuals ages 0-14 at diagnosis with one of 19 cancers. Cases and controls were frequency matched by birth year. We used logistic regression to estimate ORs and 95% confidence intervals (95% CI) as the measure of association between C-section and cancer. We assessed sex-C-section interactions for each cancer and conducted stratified analyses in acute lymphoblastic leukemia (ALL) for birth year, age at diagnosis, and maternal race. There were 3,166 cases and 20,589 controls. One third (n = 1,174) of controls born during 2004-2014 were delivered via C-section compared with 42.2% of cases (n = 285). C-section was associated with ALL (n = 819; OR: 1.20; 95% CI: 1.01-1.43) and hepatoblastoma (n = 50; OR: 1.89; 95% CI: 1.03-3.48), particularly among females (ALL OR: 1.34; 95% CI: 1.04-1.72; hepatoblastoma OR: 3.87; 95% CI: 1.30-11.57). The risk of ALL was highest during 2005-2014 (OR: 1.62; 95% CI: 1.11-2.34) and among children ages 1-5 years (OR: 1.28; 95% CI: 1.02-1.61). C-section was associated with an increased risk of ALL and hepatoblastoma. These associations require investigation to determine causality and rule out confounding by indication or reverse causality. The mechanisms underlying these associations may depend on neonatal immune system processes altered during C-section deliveries.