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Background: First Nations Peoples endure disproportionate rates of stillbirth compared with non-First Nations Peoples. Previous interventions have aimed at reducing stillbirth in First Nations Peoples and providing better bereavement care without necessarily understanding the perceptions, knowledge and beliefs that could influence the design of the intervention and implementation., Aim: The aim of this review was to understand the perceptions, knowledge and beliefs about stillbirth prevention and bereavement of First Nations Peoples from the US, Canada, Aotearoa/New Zealand, and Australia., Methods: This review was conducted in accordance with the JBI methodology for a convergent integrated mixed method systematic review. This review was overseen by an advisory board of Aboriginal Elders, researchers, and clinicians. A search of eight databases (PubMed, MEDLINE, PsycInfo, CINAHL, Embase, Emcare, Dissertations and Theses and Indigenous Health InfoNet) and grey literature was conducted. All studies were screened, extracted, and appraised for quality by two reviewers and results were categorised, and narratively summarised., Results: Ten studies were included within this review. Their findings were summarised into four categories: safeguarding baby, traditional practices of birthing and grieving, bereavement photography and post-mortem examination. The results indicate a diversity of perceptions, knowledge and beliefs primarily around smoking cessation and bereavement practices after stillbirth. However, there was a paucity of research available., Conclusions: Further research is needed to understand the perceptions, knowledge and beliefs about stillbirth among First Nations Peoples. Without research within this area, interventions to prevent stillbirth and support bereaved parents and their communities after stillbirth may face barriers to implementation., Competing Interests: Conflict of interest None declared., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Australian Aboriginal and Torres Strait Islander women with diabetes in pregnancy (DIP) are more likely to have glycaemic levels above the target range, and their babies are thus at higher risk of excessive fetal growth. Shoulder dystocia, defined by failure of spontaneous birth of fetal shoulder after birth of the head requiring obstetric maneuvers, is an obstetric emergency that is strongly associated with DIP and fetal size. The aim of this study was to investigate the epidemiology of shoulder dystocia in Aboriginal babies born to mothers with DIP., Methods: Stratifying by Aboriginal status, characteristics of births complicated by shoulder dystocia in women with and without DIP were compared and incidence and time-trends of shoulder dystocia were described. Compliance with guidelines aiming at preventing shoulder dystocia in women with DIP were compared. Post-logistic regression estimation was used to calculate the population attributable fractions (PAFs) for shoulder dystocia associated with DIP and to estimate probabilities of shoulder dystocia in babies born to mothers with DIP at birthweights > 3 kg., Results: Rates of shoulder dystocia from vaginal births in Aboriginal babies born to mothers with DIP were double that of their non-Aboriginal counterparts (6.3% vs 3.2%, p < 0.001), with no improvement over time. Aboriginal mothers with diabetes whose pregnancies were complicated by shoulder dystocia were more likely to have a history of shoulder dystocia (13.1% vs 6.3%, p = 0.032). Rates of guideline-recommended elective caesarean section in pregnancies with diabetes and birthweight > 4.5 kg were lower in the Aboriginal women (28.6% vs 43.1%, p = 0.004). PAFs indicated that 13.4% (95% CI: 9.7%-16.9%) of shoulder dystocia cases in Aboriginal (2.7% (95% CI: 2.1%-3.4%) in non-Aboriginal) women were attributable to DIP. Probability of shoulder dystocia among babies born to Aboriginal mothers with DIP was higher at birthweights > 3 kg., Conclusions: Aboriginal mothers with DIP had a higher risk of shoulder dystocia and a stronger association between birthweight and shoulder dystocia. Many cases were recurrent. These factors should be considered in clinical practice and when counselling women., (© 2024. The Author(s).)

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., (© 2023 UICC.)

Background: Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have a high prevalence of diabetes in pregnancy (DIP), which includes pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM). We aimed to characterize the impact of DIP in babies born to Aboriginal mothers., Methods: A retrospective cohort study, using routinely collected linked health data that included all singleton births (N = 510 761) in Western Australia between 1998 and 2015. Stratified by Aboriginal status, generalized linear mixed models quantified the impact of DIP on neonatal outcomes, estimating relative risks (RRs) with 95% CIs. Ratio of RRs (RRRs) examined whether RRs differed between Aboriginal and non-Aboriginal populations., Results: Exposure to DIP increased the risk of adverse outcomes to a greater extent in Aboriginal babies. PGDM heightened the risk of large for gestational age (LGA) (RR: 4.10, 95% CI: 3.56-4.72; RRR: 1.25, 95% CI: 1.09-1.43), macrosomia (RR: 2.03, 95% CI: 1.67-2.48; RRR: 1.39, 95% CI: 1.14-1.69), shoulder dystocia (RR: 4.51, 95% CI: 3.14-6.49; RRR: 2.19, 95% CI: 1.44-3.33) and major congenital anomalies (RR: 2.14, 95% CI: 1.68-2.74; RRR: 1.62, 95% CI: 1.24-2.10). GDM increased the risk of LGA (RR: 2.63, 95% CI: 2.36-2.94; RRR: 2.00, 95% CI: 1.80-2.22), macrosomia (RR: 1.95, 95% CI: 1.72-2.21; RRR: 2.27, 95% CI: 2.01-2.56) and shoulder dystocia (RR: 2.78, 95% CI: 2.12-3.63; RRR: 2.11, 95% CI: 1.61-2.77). Birthweight mediated about half of the DIP effect on shoulder dystocia only in the Aboriginal babies., Conclusions: DIP differentially increased the risks of fetal overgrowth, shoulder dystocia and congenital anomalies in Aboriginal babies. Improving care for Aboriginal women with diabetes and further research on preventing shoulder dystocia among these women can reduce the disparities., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: Maternal mental disorders have been associated with adverse perinatal outcomes such as low birthweight and preterm birth, although these links have been examined rarely among Australian Aboriginal populations. We aimed to evaluate the association between maternal mental disorders and adverse perinatal outcomes among Aboriginal births., Methods: We used whole population-based linked data to conduct a retrospective cohort study ( N  = 38,592) using all Western Australia singleton Aboriginal births (1990-2015). Maternal mental disorders were identified based on the International Classification of Diseases diagnoses and grouped into six broad diagnostic categories. The perinatal outcomes evaluated were preterm birth, small for gestational age, perinatal death, major congenital anomalies, foetal distress, low birthweight and 5-minute Apgar score. We employed log-binomial/-Poisson models to calculate risk ratios and 95% confidence intervals., Results: After adjustment for sociodemographic factors and pre-existing medical conditions, having a maternal mental disorder in the five years before the birth was associated with adverse perinatal outcomes, with risk ratios (95% confidence intervals) ranging from 1.26 [1.17, 1.36] for foetal distress to 2.00 [1.87, 2.15] for low birthweight. We found similar associations for each maternal mental illness category and neonatal outcomes, with slightly stronger associations when maternal mental illnesses were reported within 1 year rather than 5 years before birth and for substance use disorder., Conclusions: This large population-based study demonstrated an increased risk of several adverse birth outcomes among Aboriginal women with mental disorders. Holistic perinatal care, treatment and support for women with mental disorders may reduce the burden of adverse birth outcomes.

Purpose: There is scant literature about the management of stillbirth and the subsequent risk of severe maternal morbidity (SMM). We aimed to assess the risk of SMM associated with stillbirths compared with live births and whether this differed by the presence of maternal comorbidities., Methods: In this retrospective cohort study, we used a population-based dataset of all stillbirths and live births ≥ 20 weeks' gestation in Western Australia between 2000 and 2015. SMM was identified using a published Australian composite for use with routinely collected hospital morbidity data. Maternal comorbidities were identified in the Hospital Morbidity Data Collection or the Midwives Notification System using a modified Australian chronic disease composite. Multivariable Poisson regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for factors associated with SMM in analyses stratified by the presence of maternal comorbidities. Singleton and multiple pregnancies were examined separately., Results: This study included 458,639 singleton births (2319 stillbirths and 456,320 live births). The adjusted RRs for SMM among stillbirths were 2.30 (95% CI 1.77, 3.00) for those without comorbidities and 4.80 (95% CI 4.11, 5.59) (Interaction P value < 0.0001) for those with comorbidities compared to live births without and with comorbidities, respectively., Conclusion: In Western Australia between 2000 and 2015, mothers of stillbirths both with and without any maternal comorbidities had an increased risk of SMM compared with live births. Further investigation into why women who have had a stillbirth without any existing conditions or pregnancy complications develop SMM is warranted., (© 2022. The Author(s).)

Objective: The objective of this review is to investigate First Nations populations' perceptions, knowledge, attitudes, beliefs, and myths about stillbirth., Introduction: First Nations populations experience disproportionate rates of stillbirth compared with non-First Nations populations. There has been a surge of interventions aimed at reducing stillbirth and providing better bereavement care, but these are not necessarily appropriate for First Nations populations. As a first step toward developing appropriate interventions for these populations, this review will examine current perceptions, knowledge, attitudes, beliefs, and myths about stillbirth held by First Nations people from the United States, Canada, Aotearoa/New Zealand, and Australia., Inclusion Criteria: The review will consider studies that include individuals of any age (bereaved or non-bereaved) who identify as belonging to First Nations populations. Eligible studies will include the perceptions, knowledge, attitudes, beliefs, and myths about stillbirth among First Nations populations., Methods: This review will follow the JBI methodology for convergent mixed methods systematic reviews. The review is supported by an advisory panel of Aboriginal elders, lived-experience stillbirth researchers, Aboriginal researchers, and clinicians. PubMed, MEDLINE (Ovid), CINAHL (EBSCOhost), Embase (Ovid), Emcare (Ovid), PsycINFO (EBSCOhost), Indigenous Health InfoNet, Trove, Informit, and ProQuest Dissertations and Theses will be searched for relevant information. Titles and abstracts of potential studies will be screened and examined for eligibility. After critical appraisal, quantitative and qualitative data will be extracted from included studies, with the former "qualitized" and the data undergoing a convergent integrated approach., Review Registration: PROSPERO CRD42023379627., Competing Interests: DP, ZM, SH, CV, and CS are paid employees of JBI, The University of Adelaide. CS is deputy editor in chief of JBI Evidence Synthesis , but was not involved in the editorial processing of this manuscript. The other authors declare no conflicts of interest., (Copyright © 2023 JBI.)

This population-based study investigated the association of BMI and other predictors with gestational diabetes mellitus (GDM) among Australian Aboriginal and non-Aboriginal mothers. We conducted a state-wide retrospective cohort study that included all singleton births in Western Australia (n = 134,552) between 2012 and 2015 using population health datasets linked by the Western Australian Data Linkage Branch. Associations between GDM and its predictors were estimated as adjusted relative risks (aRRs) from multivariable generalised linear models. Adjusted ratio of relative risks (aRRRs) compared RRs in Aboriginal and non-Aboriginal mothers. Adjusted population attributable fractions estimated the contribution of overweight/obesity to GDM burden, and adjusted predicted probabilities for GDM were plotted against BMI levels. The following predictors had stronger associations with GDM in Aboriginal, compared to non-Aboriginal, mothers: maternal obesity (aRR [95% CI] 3.16 [2.54-3.93]; aRRR 1.57 [1.26-1.94]), previous LGA (aRR 1.70 [1.37-2.12]; aRRR 1.41 [1.13-1.76]) and previous macrosomia (birthweight ≥ 4 kg) (aRR 1.55 [1.24-1.94]; aRRR 1.53 [1.22-1.91]). 46.1% (95% CI: 36.6-54.1) of GDM cases in Aboriginal women (23.3% in non-Aboriginal mothers, 95% CI: 21.6-25.1) were attributed to overweight/obesity. Compared to non-Aboriginal mothers, adjusted GDM probabilities were higher at all BMI levels and showed greater increase with BMI. Overweight/obesity is a key driver of GDM among Aboriginal women. Association between BMI and GDM is stronger in Aboriginal, compared to non-Aboriginal, women especially at higher BMI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Background: Having a preterm (<37 weeks' gestation) birth may increase a woman's risk of early mortality. Aboriginal and Torres Strait Islander (hereafter Aboriginal) women have higher preterm birth and mortality rates compared with other Australian women., Objectives: We investigated whether a history of having a preterm birth was associated with early mortality in women and whether these associations differed by Aboriginal status., Methods: This retrospective cohort study used population-based perinatal records of women who had a singleton birth between 1980 and 2015 in Western Australia linked to Death Registry data until June 2018. The primary and secondary outcomes were all-cause and cause-specific mortality respectively. After stratification by Aboriginal status, rate differences were calculated, and Cox proportional hazard regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cause-specific mortality., Results: There were 20,244 Aboriginal mothers (1349 deaths) and 457,357 non-Aboriginal mothers (7646 deaths) with 8.6 million person-years of follow-up. The all-cause mortality rates for Aboriginal mothers who had preterm births and term births were 529.5 and 344.0 (rate difference 185.5, 95% CI 135.5, 238.5) per 100,000 person-years respectively. Among non-Aboriginal mothers, the corresponding figures were 125.5 and 88.6 (rate difference 37.0, 95% CI 29.4, 44.9) per 100,000 person-years. The HR for all-cause mortality for Aboriginal and non-Aboriginal mothers associated with preterm birth were 1.48 (95% CI 1.32, 1.66) and 1.35 (95% CI 1.26, 1.44), respectively, compared with term birth. Compared with mothers who had term births, mothers of preterm births had higher relative risks of mortality from diabetes, cardiovascular, digestive and external causes., Conclusions: Both Aboriginal and non-Aboriginal women who had a preterm birth had a moderately increased risk of mortality up to 38 years after the birth, reinforcing the importance of primary prevention and ongoing screening., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL. In unconditional multivariable logistic regression analyses of pooled data, we observed decreased odds of ALL among children breastfed 4 to 6 months (0.88, 95% CI 0.81-0.96) or 7 to 12 months (OR 0.85, 0.79-0.92). We observed a similar inverse association between breastfeeding ≥4 months and AML (0.82, 95% CI 0.71-0.95). Odds of ALL were reduced among children exclusively breastfed 4 to 6 months (OR 0.73, 95% CI 0.63-0.85) or 7 to 12 months (OR 0.70, 95% CI 0.53-0.92). Random effects metaanalyses produced similar estimates, and findings were unchanged in sensitivity analyses adjusted for race/ethnicity or mode of delivery, restricted to children diagnosed ≥1 year of age or diagnosed with B-ALL. Our pooled analyses indicate that longer breastfeeding is associated with decreased odds of ALL and AML. Few risk factors for ALL and AML have been described, therefore our findings highlight the need to promote breastfeeding for leukemia prevention., (© 2022 UICC.)

Background: It is known that a previous preterm birth increases the risk of a subsequent preterm birth, but a limited number of studies have examined this beyond two consecutive pregnancies., Aims: This study aimed to assess the risk and patterns of (recurrent) preterm birth up to the fourth pregnancy., Materials and Methods: We used Western Australian routinely linked population health datasets to identify women who had two or more consecutive singleton births (≥20 weeks gestation) from 1980 to 2015. A log-binomial model was used to calculate risk ratios (RRs) and 95% confidence interval (CIs) for preterm birth risk in the third and fourth deliveries by the combined outcomes of previous pregnancies., Results: We analysed 255 435 women with 651 726 births. About 7% of women had a preterm birth in the first delivery, and the rate of continuous preterm birth recurrence was 22.9% (second), 44.9% (third) and 58.5% (fourth) deliveries. The risk of preterm birth at the third delivery was highest for women with two prior indicated preterm births (RR 12.5, 95% CI: 11.3, 13.9) and for those whose first pregnancy was 32-36 weeks gestation, and second pregnancy was less than 32 weeks gestation (RR 11.8, 95% CI: 10.3, 13.5). There were similar findings for the second and fourth deliveries., Conclusions: Our findings demonstrate that women with any prior preterm birth were at greater risk of preterm birth in subsequent pregnancies compared with women with only term births, and the risk increased with shorter gestational length, and the number of previous preterm deliveries, especially sequential ones., (© 2022 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: There is scant literature about antepartum stillbirth management but guidelines usually recommend reserving caesarean sections for exceptional circumstances. However, little is known about caesarean section rates following antepartum stillbirth in Australia., Aims: We aimed to describe the onset of labour, mode of birth, and use of analgesia and anaesthesia following antepartum stillbirth and to identify factors associated with caesarean section., Material and Methods: In this retrospective cohort study, we used a population-based dataset of all singleton antepartum stillbirths ≥20 weeks gestation in Western Australia between 2010-2015. The overall, primary and repeat caesarean section rates for antepartum stillbirths were calculated and multivariable Poisson regression analyses were performed to identify associated factors, and to calculate relative risks (RRs) and 95% confidence intervals (CIs)., Results: This study included 634 antepartum stillbirths. Labour was spontaneous for 134 (21.1%), induced for 457 (72.1%), and 43 (6.8%) had a prelabour caesarean section. The overall, primary and repeat caesarean section rates were 8.5%, 4.6% and 23.0% respectively and increased with gestation (P trends all <0.01). Other factors associated with an increased caesarean section risk included: any placenta praevia or placental abruption, birth at a metropolitan private hospital, large-for-gestational-age birthweight, and any maternal chronic condition. During labour, the most frequently used types of analgesia were systemic narcotics (46.0%) and regional blocks (34.7%) while among those who had a caesarean section, 40.7% had a general anaesthetic., Conclusions: In Western Australia between 2010-2015, the caesarean section rates among women with antepartum stillbirths were low, in line with current guidelines., (© 2022 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Background: Diabetes in pregnancy (DIP), which includes pre-gestational and gestational diabetes, is more prevalent among Aboriginal women. DIP and its adverse neonatal outcomes are associated with diabetes and cardiovascular disease in the offspring. This study investigated the impact of DIP on trends of large for gestational age (LGA) in Aboriginal and non-Aboriginal populations, and added to the limited evidence on temporal trends of DIP burden in these populations., Methods: We conducted a retrospective cohort study that included all births in Western Australia between 1998 and 2015 using linked population health datasets. Time trends of age-standardised and crude rates of pre-gestational and gestational diabetes were estimated in Aboriginal and non-Aboriginal mothers. Mixed-effects multivariable logistic regression was used to estimate the association between DIP and population LGA trends over time., Results: Over the study period, there were 526,319 births in Western Australia, of which 6.4% were to Aboriginal mothers. The age-standardised annual rates of pre-gestational diabetes among Aboriginal mothers rose from 4.3% in 1998 to 5.4% in 2015 and remained below 1% in non-Aboriginal women. The comparable rates for gestational diabetes increased from 6.7 to 11.5% over the study period in Aboriginal women, and from 3.5 to 10.2% among non-Aboriginal mothers. LGA rates in Aboriginal babies remained high with inconsistent and no improvement in pregnancies complicated by gestational diabetes and pre-gestational diabetes, respectively. Regression analyses showed that DIP explained a large part of the increasing LGA rates over time in Aboriginal babies., Conclusions: There has been a substantial increase in the burden of pre-gestational diabetes (Aboriginal women) and gestational diabetes (Aboriginal and non-Aboriginal) in recent decades. DIP appears to substantially contribute to increasing trends in LGA among Aboriginal babies., (© 2022. The Author(s).)

Background: The health disadvantages faced by Australian Aboriginal peoples are evidenced in early life, although few studies have focused on the reasons for population-level inequalities in more severe adverse outcomes. This study aimed to examine the scale of disparity in severe neonatal morbidity (SNM) and mortality between Aboriginal and non-Aboriginal births and quantify the relative contributions of important maternal and infant factors., Method: A retrospective cohort study with singleton live births (≥32 weeks' gestation) was conducted using Western Australia linked whole population datasets, from 1999 to 2015. Aboriginal status was determined based on the mothers' self-reported ethnic origin. An Australian validated indicator was adapted to identify neonates with SNM. The Oaxaca-Blinder method was employed to calculate the contribution of each maternal and infant factor to the disparity in SNM and mortality., Results: Analyses included 425 070 births, with 15 967 (3.8%) SNM and mortality cases. The disparity in SNM and mortality between Aboriginal and non-Aboriginal births was 2.9 percentage points (95% CI 2.6 to 3.2). About 71% of this gap was explained by differences in modelled factors including maternal area of residence (23.8%), gestational age (22.2%), maternal age (7.5%) and antenatal smoking (7.2%)., Conclusions: There is a considerable disparity in SNM and mortality between Aboriginal and non-Aboriginal births in Western Australia with the majority of this related to differences in maternal sociodemographic factors, antenatal smoking and gestational age. Public health programmes targeting these factors may contribute to a reduction in early life health differentials and benefit Aboriginal population health through the life course., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Evidence about the association between maternal mental health disorders and stillbirth and infant mortality is limited and conflicting. We aimed to examine whether maternal prenatal mental health disorders are associated with stillbirth and/or infant mortality. MEDLINE, Embase, PsycINFO, and Scopus were searched for studies examining the association of any maternal prenatal (occurring before or during pregnancy) mental health disorder(s) and stillbirth or infant mortality. A random-effects meta-analysis was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). The between-study heterogeneity was quantified using the I 2 statistic. Subgroup analyses were performed to identify the source of heterogeneity. Of 4487 records identified, 28 met our inclusion criteria with 27 contributing to the meta-analyses. Over 60% of studies examined stillbirth and 54% of them evaluated neonatal or infant mortality. Thirteen studies investigated the association between maternal depression and anxiety and stillbirth/infant mortality, pooled OR, 1.42 (95% CI, 1.16-1.73; I 2 , 76.7%). Another 13 studies evaluated the association between severe maternal mental illness and stillbirth/infant mortality, pooled OR, 1.47 (95% CI, 1.28-1.68; I 2 , 62.3%). We found similar results for the association of any maternal mental health disorders and stillbirth/infant mortality (OR, 1.59; 95% CI, 1.43-1.77) and in subgroup analyses according to types of fetal/infant mortality. We found no significant evidence of publication bias. Maternal prenatal mental health disorders appear to be associated with a moderate increase in the risk of stillbirth and infant mortality, although the mechanisms are unclear. Efforts to prevent and treat these disorders may reduce the scale of stillbirth/infant deaths.

Background: Stillbirth is a critical public health issue worldwide. While the rates in high-income countries are relatively low, there are persistent between-country disparities., Objectives: To compare stillbirth rates and trends in Wales and the State of Western Australia (WA), Australia, and provide insights into any differences., Methods: In this international retrospective cohort study, we pooled population-based data collections of all births ≥24 weeks' gestation (excluding terminations for congenital anomalies) between 1993 and 2015, divided into six time periods. The stillbirth rate per 1000 births was estimated for each cohort in each time period. Multivariable Poisson regression analyses, adjusted for appropriateness of growth, socio-economic status, maternal age, and multiple birth, were performed to evaluate the interaction between cohort and time period. Relative risk (RR) and 95% confidence interval (CI) for each time period and cohort were calculated., Results: There were 767 731 births (3725 stillbirths) in Wales and 648 373 (2431 stillbirths) in WA. The overall stillbirth rate declined by 15.9% over the study period in Wales (from 5.3 in 1993-96 to 4.5 per 1000 births in 2013-15; P trend  < .01) but by 40.4% in WA (from 4.9 to 2.9 per 1000 births in WA; P trend  < .01). Using 1993-96 in WA as the reference group, the adjusted RRs for stillbirths at 37-38 weeks' gestation in the most recent study period (2013-15) were 0.85 (95% CI 0.64, 1.13) in Wales and 0.51 (95% CI 0.36, 0.73) in WA., Conclusions: The stillbirth rates between Wales and WA have widened in the last two decades (especially among late-term births), although the absolute rates for both are distinctly higher than the best-performing nations. While the differences may be partly explained by timing of birth and maternal life style behaviours such as smoking, it is important to identify and ameliorate the associated risk factors to support a reduction in preventable stillbirths., (© 2020 John Wiley & Sons Ltd.)

Objectives: To assess the scale of ethnic inequalities in severe maternal morbidity (SMM) rates and quantify the contribution of maternal characteristics to these disparities., Design: Retrospective cohort study., Setting: Whole-of-population linked administrative data from 2002 to 2015 in Western Australia., Participants: Women with 410 043 birth events (includes all births from the same pregnancy) of 20 weeks' or more gestation, including terminations for congenital anomalies., Primary and Secondary Outcome Measures: Women with SMM were identified based on a composite indicator of SMM using diagnosis and procedure codes developed for use in routinely collected data. Mothers were classified into seven ethnic groups, based on their reported ethnic origin. The associations between maternal ethnic origin and SMM were examined using a log-binomial model, which estimates risk ratios (RRs) and 95% CIs. The Blinder-Oaxaca decomposition technique was employed to partition the disparity in SMM between Aboriginal and Caucasian populations into 'explained' and 'unexplained' components., Results: During the study period, 9378 SMM cases were documented. In the adjusted model, Aboriginal (RR 1.73, 95% CI 1.59 to 1.87), African (RR 1.64, 95% CI 1.43 to 1.89) and 'other' ethnicity (RR 1.49, 95% CI 1.37 to 1.63) women were at significantly higher risk of SMM compared with Caucasian women. Teenage and older mothers and socioeconomically disadvantaged women were also at greater risk of SMM. Differences in sociodemographic characteristics explained 33.2% of the disparity in SMM between Aboriginal and Caucasian women., Conclusions: There are distinct disparities in SMM by ethnicity in Western Australia, with a greater risk among Aboriginal and African women. While improvements in SES and a reduction in teenage pregnancy can potentially support a sizeable reduction in SMM rate inequalities, future research should investigate other potential pathways and targeted interventions to close the ethnicity disparity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Pesticide exposure is a suspected risk factor for childhood cancer. We investigated the risk of developing childhood cancer in relation to parental occupational exposure to pesticides in Switzerland for the period 1990-2015., Methods: From a nationwide census-based cohort study in Switzerland, we included children aged < 16 years at national censuses of 1990 and 2000 and followed them until 2015. We extracted parental occupations reported at the census closest to the birth year of the child and estimated exposure to pesticides using a job exposure matrix. Cox proportional hazards models, adjusted for potential confounders, were fitted for the following outcomes: any cancer, leukaemia, central nervous system tumours (CNST), lymphoma, non-CNS solid tumours., Results: Analyses of maternal (paternal) exposure were based on approximately 15.9 (15.1) million-person years at risk and included 1891 (1808) cases of cancer, of which 532 (503) were leukaemia, 348 (337) lymphomas, 423 (399) CNST, and 588 (569) non-CNS solid tumours. The prevalence of high likelihood of exposure was 2.9% for mothers and 6.7% for fathers. No evidence of an association was found with maternal or paternal exposure for any of the outcomes, except for "non-CNS solid tumours" (High versus None; Father: adjusted HR [95%CI] =1.84 [1.31-2.58]; Mother: 1.79 [1.13-2.84]). No evidence of an association was found for main subtypes of leukaemia and lymphoma. A post-hoc analysis on frequent subtypes of "non-CNS solid tumours" showed positive associations with wide CIs for some cancers., Conclusion: Our study suggests an increased risk for solid tumours other than in the CNS among children whose parents were occupationally exposed to pesticides; however, the small numbers of cases limited a closer investigation of cancer subtypes. Better exposure assessment and pooled studies are needed to further explore a possible link between specific childhood cancers types and parental occupational exposure to pesticides.

Purpose: To investigate the proportion of severely growth-restricted singleton births < 3rd percentile (proxy for severe fetal growth restriction; FGR) undelivered at 40 weeks (FGR&#95;40), and compare maternal characteristics and outcomes of FGR&#95;40 births and FGR births at 37-39 weeks' (FGR&#95;37-39) to those not born small-for-gestational-age at term (Not SGA&#95;37+)., Methods: The annual rates of singleton FGR&#95;40 births from 2006 to 2015 were calculated using data from linked Western Australian population health datasets. Using 2013-2015 data, maternal factors associated with FGR births were investigated using multinomial logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI) while relative risks (RR) of birth outcomes between each group were calculated using Poisson regression. Neonatal adverse outcomes were identified using a published composite indicator (diagnoses, procedures and other factors)., Results: The rate of singleton FGR&#95;40 births decreased by 23.0% between 2006 and 2015. Factors strongly associated with FGR&#95;40 and FGR&#95;37-39 births compared to Not SGA&#95;37+ births included the mother being primiparous (ORs 3.13: 95% CI 2.59-3.79; 1.69, 95% CI 1.47, 1.94, respectively) and ante-natal smoking (ORs 2.55, 95% CI 1.97, 3.32; 4.48, 95% CI 3.74, 5.36, respectively). FGR&#95;40 and FGR&#95;37-39 infants were more likely to have a neonatal adverse outcome (RRs 1.70, 95% CI 1.41, 2.06 and 2.46 95% CI 2.18, 2.46, respectively) compared to Not SGA 37+ infants., Conclusions: Higher levels of poor perinatal outcomes among FGR births highlight the importance of appropriate management including fetal growth monitoring. Regular population-level monitoring of FGR&#95;40 rates may lead to reduced numbers of poor outcomes.

Introduction: Maternal mental health disorders such as anxiety and depression are major public health concerns. Evidence shows a link between maternal mental health disorders and preterm birth and low birth weight. However, the impacts of maternal mental health disorders on stillbirth and infant mortality have been less investigated and inconsistent findings have been reported. Thus, using the available literature, we plan to examine whether prenatal maternal mental health disorders impact the risk of stillbirth and infant mortality., Methods and Analysis: This systematic review and meta-analysis will adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and will be registered with the International Prospective Register of Systematic Reviews. Systematic searches will be conducted (from database inception to December 2019) in Medline, Embase, PsycINFO and Scopus for studies examining the association of prenatal mental health disorders and stillbirth and infant mortality. The search will be limited to studies published in English language and in humans only, with no restriction on the year of publication. Two independent reviewers will evaluate records and assess the quality of individual studies. The Newcastle-Ottawa scales and GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach will be used to assess the methodological quality and bias of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I 2 statistics will be used to assess between-study heterogeneity in the estimated effect size., Ethics and Dissemination: As it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences., Prospero Registration Number: 159834., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Quantification of stillbirth risk has potential to support clinical decision-making. Studies that have attempted to quantify stillbirth risk have been hampered by small event rates, a limited range of predictors that typically exclude obstetric history, lack of validation, and restriction to a single classifier (logistic regression). Consequently, predictive performance remains low, and risk quantification has not been adopted into antenatal practice. The study population consisted of all births to women in Western Australia from 1980 to 2015, excluding terminations. After all exclusions there were 947,025 livebirths and 5,788 stillbirths. Predictive models for stillbirth were developed using multiple machine learning classifiers: regularised logistic regression, decision trees based on classification and regression trees, random forest, extreme gradient boosting (XGBoost), and a multilayer perceptron neural network. We applied 10-fold cross-validation using independent data not used to develop the models. Predictors included maternal socio-demographic characteristics, chronic medical conditions, obstetric complications and family history in both the current and previous pregnancy. In this cohort, 66% of stillbirths were observed for multiparous women. The best performing classifier (XGBoost) predicted 45% (95% CI: 43%, 46%) of stillbirths for all women and 45% (95% CI: 43%, 47%) of stillbirths after the inclusion of previous pregnancy history. Almost half of stillbirths could be potentially identified antenatally based on a combination of current pregnancy complications, congenital anomalies, maternal characteristics, and medical history. Greatest sensitivity is achieved with addition of current pregnancy complications. Ensemble classifiers offered marginal improvement for prediction compared to logistic regression.

Neuroblastoma (NB) is the most common extra-cranial tumour in children. Little is known about the aetiology of NB. The early age at onset and the embryonic nature suggest a role for perinatal exposures. We conducted a pooled analysis of two French national population-based case-control studies to explore whether there was an association between parental smoking and alcohol consumption and the risk of NB. The mothers of 357 NB cases and 1,783 controls from general population, frequency matched by age and sex, were interviewed on demographic, socioeconomic and perinatal characteristics, maternal reproductive story, and life-style and childhood environment. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. A meta-analysis of our findings with those of previous studies was also conducted. Maternal smoking during pregnancy was slightly more often reported for the cases (24.1%) than for the controls (19.7%) (OR 1.3 [95% CI 0.9-1.7]; summary OR from meta-analysis 1.1 [95% CI 1.0-1.3]. Paternal smoking in the year before child's birth were not associated with NB as independent exposure (OR 1.1 [95% CI 0.9-1.4] but the association was stronger when both parents reported having smoked during pregnancy (OR 1.5 [95% CI 1.1-2.1]. No association was observed with maternal alcohol intake during pregnancy (OR 1.0 [95% CI 0.8-1.4], summary OR from meta-analysis 1.0 [95% CI 0.9-1.2]. Our findings provide some evidence of an association between maternal smoking during pregnancy and NB and add another reason to recommend that women refrain from smoking during pregnancy., (© 2019 UICC.)

Background: Perinatal mortality rates are typically higher in Aboriginal than non-Aboriginal populations of Australia., Objectives: This study aimed to examine the pattern of stillbirth and neonatal mortality rate disparities over time in Western Australia, including an evaluation of these disparities across gestational age groupings., Methods: All singleton births (≥20 weeks gestation) in Western Australia between 1980 and 2015 were included. Linked data were obtained from core population health datasets of Western Australia. Stillbirth and neonatal mortality rates and percentage changes in the rates over time were calculated by Aboriginal status and gestational age categories., Results: From 1980 to 2015, data were available for 930 926 births (925 715 livebirths, 5211 stillbirths and 2476 neonatal deaths). Over the study period, there was a substantial reduction in both the Aboriginal (19.6%) and non-Aboriginal (32.3%) stillbirth rates. These reductions were evident in most gestational age categories among non-Aboriginal births and in Aboriginal term births. Concomitantly, neonatal mortality rates decreased in all gestational age windows for both populations, ranging from 32.1% to 77.5%. The overall stillbirth and neonatal mortality rate differences between Aboriginal and non-Aboriginal birth decreased by 0.6 per 1000 births and 3.9 per 1000 livebirths, respectively, although the rate ratios (RR 2.51, 95% CI 2.14, 2.94) and (RR 2.94, 95% CI 2.24, 3.85), respectively reflect a persistent excess of Aboriginal perinatal mortality across the study period., Conclusions: Despite steady improvements in perinatal mortality rates in Western Australia over 3½ decades, the gap between Aboriginal and non-Aboriginal rates remains unchanged in relative terms. There is a continuing, pressing need to address modifiable risk factors for preventable early mortality in Aboriginal populations., (© 2019 John Wiley & Sons Ltd.)

Purpose: The aim of this systematic review was to evaluate the associations between pre-pregnancy body mass index and gestational weight gain and placental abruption., Methods: Relevant studies were identified from PubMed, EMBASE, Scopus and CINAHL. Unpublished findings from analyses of linked population-based data sets from Western Australia (2012-2015, n = 114,792) were also included. Studies evaluating pre-pregnancy body mass index and/or gestational weight gain and placental abruption were included. Two independent reviewers evaluated studies for inclusion and quality. Data including odds ratios (ORs) and 95% confidence intervals (CIs) were extracted and analysed by random effects meta-analysis., Results: 21 studies were included, of which 15 were eligible for meta-analyses. The summary ORs for the association of being underweight, overweight and obese, and placental abruption, compared to normal weight women, were 1.4 (95% CI 1.1, 1.7), 0.8 (95% CI 0.8, 0.9) and 0.8 (95% CI 0.7, 0.9), respectively. These findings remained unchanged when each study was eliminated from the analysis and in subgroup analyses. Although data were scarce, women with gestational weight gain below the Institute of Medicine recommendations appeared to be at greater risk of abruption compared with women who had optimal weight gain., Conclusions: Mothers that are underweight prior to or in early pregnancy are at a moderately increased risk of placental abruption.

Purpose: Although some specific genetic syndromes such as neurofibromatosis (NF) have been identified as risk factor of childhood brain tumors (CBT), the potential role of inherited susceptibility in CBT has yet to be elucidated., Methods: To further investigate this, we conducted a pooled analysis of two nationwide case-control studies ESCALE and ESTELLE. The mothers of 509 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, responded to a telephone interview conducted by trained interviewers. Pooled odds ratio (OR) and 95% confidence intervals (95% CI) were estimated using unconditional logistic regression., Results: CBT was significantly associated with the family history of cancer in relatives (OR 1.2, 95% CI 1.0-1.5). The OR was slightly higher for maternal relatives than for paternal relatives, and when at least two relatives had a history of cancer. CBT was significantly associated with a family history of brain tumor (OR 2.1, 95% CI 1.3-3.7). This association seemed stronger for first-degree relatives (mother, father, and siblings), for whom, by contrast, no association was seen for cancers other than CBT. No specificity by CBT subtypes or by age of the children were found for any of these findings., Conclusion: Our findings support the hypothesis of a familial susceptibility of CBT, not due to being a known NF carrier.

Purpose: The early onset of childhood acute lymphoblastic leukemia (ALL) suggests that critical exposures occurring during pregnancy may increase risk. We investigated the effects of maternal coffee and tea consumption during pregnancy on ALL risk by pooling data from eight case-control studies participating in the Childhood Leukemia International Consortium., Method: Data on maternal coffee intake were available for 2,552 cases and 4,876 controls, and data on tea intake were available for 2,982 cases and 5,367 controls. Coffee and tea intake was categorized into 0, > 0-1, > 1-2, and > 2 cups/day, and covariates were combined and harmonized. Data on genetic variants in NAT2, CYP1A1, and NQO1 were also available in a subset. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression, and linear trends across categories were assessed., Results: No association was seen with 'any' maternal coffee consumption during pregnancy, but there was evidence of a positive exposure-response; the pooled OR for > 2 cups/day versus none was 1.27 (95% CI 1.09-1.43), p trend = 0.005. No associations were observed with tea consumption. No interactions were seen between coffee or tea intake and age, maternal smoking or genotype, and there was little or no evidence that associations with coffee or tea differed among cases with and without chromosomal translocations., Conclusions: Despite some limitations, our findings suggest that high coffee intake during pregnancy may increase risk of childhood ALL. Thus, current advice to limit caffeine intake during pregnancy to reduce risk of preterm birth may have additional benefits.

The associations between childhood acute lymphoblastic leukemia (ALL) and several factors related to early stimulation of the immune system, that is, farm residence and regular contacts with farm animals (livestock, poultry) or pets in early childhood, were investigated using data from 13 case-control studies participating in the Childhood Leukemia International Consortium. The sample included 7847 ALL cases and 11,667 controls aged 1-14 years. In all studies, the data were obtained from case and control parents using standardized questionnaires. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Contact with livestock in the first year of life was inversely associated with ALL (OR = 0.65, 95% CI: 0.50, 0.85). Inverse associations were also observed for contact with dogs (OR = 0.92, 95% CI: 0.86, 0.99) and cats (OR = 0.87, 95% CI: 0.80, 0.94) in the first year of life. There was no evidence of a significant association with farm residence in the first year of life. The findings of these large pooled and meta-analyses add additional evidence to the hypothesis that regular contact with animals in early childhood is inversely associated with childhood ALL occurrence which is consistent with Greaves' delayed infection hypothesis., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Some previous epidemiological studies have suggested that pesticide exposure during pregnancy may have a possible role in the development of childhood brain tumors (CBT). We pooled data from two French national population-based, case-control studies to investigate the association between maternal residential use of pesticides during pregnancy and the risk of CBT. The mothers of 437 CBT cases and 3,102 controls aged under 15 years who resided in France at diagnosis/interview, frequency-matched by age and gender, answered a structured telephone interview conducted by trained interviewers. Unconditional logistic regression was used to estimate pooled odds ratio (OR) and 95% confidence intervals (95% CI). CBT was significantly associated with the maternal home use of pesticides during pregnancy (OR 1.4, 95% CI 1.2-1.8) and, more specifically, with insecticide (OR 1.4, 1.2-1.8). We could not draw any conclusions about herbicides and/or fungicides because few women used them during pregnancy and most of these mothers also used insecticides. Although potential recall bias cannot be excluded, our findings of this pooled analysis support the hypothesis that residential maternal use of pesticides during pregnancy and particularly insecticides may increase the risk of CBT. Future investigations to verify these findings and to explore for CBT subtypes and dose-response are necessary to have a better understanding of the possible role of pesticides in etiology of CBT., (© 2017 UICC.)

Background: Few studies have investigated whether early infections and factors potentially related to early immune stimulation might be involved in the aetiology of childhood brain tumours (CBT). In this study, we investigated the associations between CBT with early day-care attendance, history of early common infections, atopic conditions (asthma/wheezing, eczema, allergic rhinitis), early farm residence/visits and contact with animals., Methods: We pooled data from two nationwide French case-control studies, the ESCALE and ESTELLE studies. Children with a CBT diagnosed between 1 and 14 years of age were identified directly from the French National Registry of Childhood Cancers, while population controls were recruited from telephone subscribers. Odds-ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression adjusted for potential confounders., Results: The analyses included 469 cases and 2719 controls. We found no association between attending a day-care centre (OR: 0.9, 95%CI: 0.7-1.2) or having had repeated common infections (OR: 0.9, 95%CI: 0.7-1.2) in the first year of life and the risk of CBT. There was also no association with a history of asthma/wheezing (OR: 0.8, 95%CI: 0.56-1.1). Farm visits (OR: 0.6, 95%CI: 0.5-0.8) as well as contact with pets (OR: 0.8, 95%CI: 0.6-1.0) in the first year of life were inversely associated with CBT., Conclusions: Our findings suggest a protective effect of early farm visits and contact with pets, but not with other markers of early immune stimulation. This might be related to immune stimulation but needs further investigation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

We are continually bombarded by information arriving to each of our senses; however, the brain seems to effortlessly integrate this separate information into a unified percept. Although multisensory integration has been researched extensively using simple computer tasks and stimuli, much less is known about how multisensory integration functions in real-world contexts. Additionally, several recent studies have demonstrated that multisensory integration varies tremendously across naturalistic stimuli. Virtual reality can be used to study multisensory integration in realistic settings because it combines realism with precise control over the environment and stimulus presentation. In the current study, we investigated whether multisensory integration as measured by the redundant signals effects (RSE) is observable in naturalistic environments using virtual reality and whether it differs as a function of target and/or environment cue-richness. Participants detected auditory, visual, and audiovisual targets which varied in cue-richness within three distinct virtual worlds that also varied in cue-richness. We demonstrated integrative effects in each environment-by-target pairing and further showed a modest effect on multisensory integration as a function of target cue-richness but only in the cue-rich environment. Our study is the first to definitively show that minimal and more naturalistic tasks elicit comparable redundant signals effects. Our results also suggest that multisensory integration may function differently depending on the features of the environment. The results of this study have important implications in the design of virtual multisensory environments that are currently being used for training, educational, and entertainment purposes.

Purpose: Neuroblastoma (NB) is an embryonic tumor that occurs almost exclusively in infancy and early childhood. While considerable evidence suggests that it may be initiated during embryonic development, the etiology of NB is still unknown. The aim of this study was to explore whether there is an association between maternal use of household pesticides during pregnancy and the risk of NB in the offspring., Methods: We conducted a pooled analysis of two French national-based case-control studies. The mothers of 357 NB cases and 1,783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on sociodemographic and perinatal characteristics, childhood environment, and life-style. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals., Results: After controlling for matching variables, study of origin, and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with NB (OR 1.5 [95% CI 1.2-1.9]). The most commonly used type of pesticides were insecticides and there was a positive association with their use alone (OR 1.4 [95% CI 1.1-1.9]) or with other pesticides (OR 2.0 [95% CI 1.1-3.4])., Conclusions: Although there is the potential for recall bias due to the study design, our findings add to the evidence of an association between the household use of pesticides and NB. Until a better study design can be found, our findings add yet another reason why to advise pregnant women to limit pesticide exposure during the periconceptional period.

Purpose: To investigate whether parental smoking around the time of pregnancy or maternal consumption of beverages (alcohol, coffee, or tea) during pregnancy were associated with the risk of CBT., Methods: We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender, were interviewed through telephone, which included questions about prenatal parental smoking and maternal consumption of alcohol, coffee and tea. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex and study of origin., Results: No association was seen between CBT and the mother smoking or drinking alcohol, coffee, or tea during the index pregnancy. The OR between CBT and paternal smoking in the year before birth (as reported by the mother) was 1.25 (95% CI 1.03, 1.52) with an OR of 1.09 (0.99, 1.19) for every 10 cigarettes per day (CPD) smoked. The association between paternal smoking and CBT appeared to be stronger in children diagnosed before the age of five years (OR 1.52, 95% CI 1.14, 2.02) and for astrocytoma (OR 1.86, 95% CI 1.26, 2.74)., Conclusion: We found some evidence of a weak association between paternal smoking in the year before the child's birth and CBT, especially astrocytomas. These findings need to be replicated in other samples, using similar classifications of tumour subtypes.

Little is known of the causes of childhood brain tumors (CBT). The aims of this study were to investigate whether extremes of birth weight were associated with increased risk of CBT and whether maternal preconceptional folic acid supplementation or breastfeeding reduced the risk. In addition, other maternal characteristics and birth related factors were also investigated. We pooled data from two French national population-based case-control studies with similar designs conducted in 2003-2004 and 2010-2011. The mothers of 510 CBT cases (directly recruited from the national childhood cancer register) and 3,102 controls aged under 15 years, frequency matched by age and gender did a telephone interview, which focussed on demographic and perinatal characteristics, and maternal life style habits and reproductive history. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional logistic regression, adjusted for age, sex, study of origin and relevant confounders. No association was found between CBT and birth weight or fetal growth. The use of preconceptional folic acid supplementation was rare (5.3% in cases and 7.8% in controls) and the OR was 0.8 (95% CI 0.5, 1.4). There was no association with breastfeeding, even prolonged (six months or more; OR 1.0, 95% CI 0.8, 1.4). Neither was there any association between CBT and other investigated factors (maternal body mass index, gestational weight gain, congenital abnormality, maternal reproductive history or use of fertility treatments. Although large, this study was underpowered for subtype analyses. Pooling data with other population-based studies may provide further insight into findings by CBT subtypes., (© 2017 UICC.)

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention., (© 2016 UICC.)

Objective: The aim of this study was to assess the risk of childhood central nervous system (CNS) tumors associated with parental occupational pesticide exposure., Methods: We pooled three population-based case-control studies from France, Germany, and the United Kingdom. Cases were children below 15 years of age with CNS tumors; controls were matched by gender and age. A general population job-exposure matrix assessed parental occupational pesticide exposure. Logistic regressions estimated odds ratios (ORs) and 95% confidence intervals (CIs)., Results: The study included 1361 cases and 5498 controls. Prevalence of maternal occupational pesticide exposure during pregnancy was low and no association with childhood CNS tumors was detected (OR 0.76, 95% CI: 0.41 to 1.41). Around conception, OR for childhood CNS tumors associated with paternal occupational pesticide exposure was 0.71 (95% CI: 0.53 to 0.95)., Conclusion: Our results do not suggest a role of parental occupational pesticide exposure in the etiology of childhood CNS tumors.

Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood., (© 2015 UICC.)

Purpose: It has been suggested that home paint exposure increases the risk of childhood acute lymphoblastic leukemia (ALL)., Methods: We obtained individual level data from eight case-control studies participating in the Childhood Leukemia International Consortium. All studies had home paint exposure data (sometimes including lacquers and varnishes) for the pregnancy period with additional data for the 1-3-month period before conception in five, the year before conception in two, and the period after birth in four studies, respectively. Cytogenetic subtype data were available for some studies. Data were harmonized to a compatible format. Pooled analyses of individual data were undertaken using unconditional logistic regression., Results: Based on 3,002 cases and 3,836 controls, the pooled odds ratio (OR) for home paint exposure in the 1-3 months before conception and risk of ALL was 1.54 [95% confidence interval (CI) 1.28, 1.85], while based on 1,160 cases and 1,641 controls for exposure in the year before conception, it was 1.00 (95% CI 0.86, 1.17). For exposure during pregnancy, using 4,382 cases and 5,747 controls, the pooled OR was 1.14 (95% CI 1.04, 1.25), and for exposure after birth, the OR was 1.22 (95% CI 1.07, 1.39), based on data from 1,962 cases and 2,973 controls. The risk was greater for certain cytogenetic subtypes and if someone other than the parents did the painting., Conclusions: Home paint exposure shortly before conception, during pregnancy, and/or after birth appeared to increase the risk of childhood ALL. It may be prudent to limit exposure during these periods., Competing Interests: The authors declare that they have no conflict of interest.

Purpose: The etiology of childhood brain tumors (CBT) is poorly understood, but dietary factors could be involved. In this case-control study of CBT, the possible associations of childhood intake of dietary and supplemental folate, vitamin B6, and vitamin B12 with the risk of CBT were investigated, along with various food groups., Methods: Cases diagnosed between 2005 and 2010 were identified from 10 pediatric oncology centers in Australia and controls by nationwide random-digit dialling. For study children of ages 3-14 years, diet in the year before diagnosis (or recruitment) was assessed using food frequency questionnaires. Folate intake was adjusted for bioavailability, and dietary micronutrient intake was energy-adjusted. Micronutrients and food groups were analyzed using logistic regression adjusting for relevant confounders. Principal components analysis was conducted to assess food group intake patterns for analysis., Results: Food and micronutrient data were available for 216 cases and 523 controls. Folate intake was associated with a reduced risk of CBT overall (odds ratio for highest tertile vs. lowest: 0.63, 95% confidence interval 0.41, 0.97) and particularly low-grade gliomas (odds ratio for highest tertile vs. lowest: 0.52, 95% confidence interval 0.29, 0.92). Vitamin B6 and B12 intake was not associated with CBT risk, nor was processed meat., Conclusions: High folate intake during childhood may reduce the risk of CBT. This potentially important finding needs to be corroborated in other studies. If replicated, these results could have important implications for public health recommendations regarding diet during childhood.

It is biologically plausible that a paternal preconception diet low in nutrients related to DNA integrity could affect sperm DNA and subsequently risk of cancer in the offspring. The aim of this analysis was to investigate whether paternal preconception dietary folate, B6, or B12 intake was associated with the risk of childhood brain tumors (CBT) in an Australian case-control study. Cases <15 years of age were recruited from 10 Australian pediatric oncology centers between 2005 and 2010, and controls from random-digit dialing, frequency-matched to cases on age, sex, and state of residence. Paternal dietary information was obtained by food-frequency questionnaires. Nutrient values were energy adjusted and divided into tertiles for analysis by unconditional logistic regression. In fathers with relevant data (237 cases and 629 controls), no association with dietary folate and B6 and risk of CBT was seen; high B12 intake was associated with an increased risk of CBT (odds ratio highest vs. lowest tertile: 1.74, 95% confidence interval: 1.14, 2.66) without an increasing trend. These results do not support the hypothesis that paternal dietary folate intake influences the risk of CBT. The increased OR observed between dietary B12 intake and risk of CBT is without any certain explanation.

Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

Background: Several studies suggest that maternal folic acid supplementation before or during pregnancy protects against childhood acute lymphoblastic leukemia (ALL). We investigated associations between ALL risk and folate pathway gene polymorphisms, and their modification by maternal folic acid supplements, in a population-based case-control study (2003-2007)., Methods: All Australian pediatric oncology centers provided cases; controls were recruited by national random digit dialing. Data from 392 cases and 535 controls were included. Seven folate pathway gene polymorphisms (MTHFR 677C>T, MTHFR 1298A>C, MTRR 66A>G, MTR 2756 A>G, MTR 5049 C>A, CBS 844 Ins68, and CBS 2199 T>C) were genotyped in children and their parents. Information on prepregnancy maternal folic acid supplement use was collected. ORs were estimated with unconditional logistic regression adjusted for frequency-matched variables and potential confounders. Case-parent trios were also analyzed., Results: There was some evidence of a reduced risk of ALL among children who had, or whose father had, the MTRR 66GG genotype: ORs 0.60 [95% confidence interval (CI) 0.39-0.91] and 0.64 (95% CI, 0.40-1.03), respectively. The ORs for paternal MTHFR 677CT and TT genotypes were 1.41 (95% CI, 1.02-1.93) and 1.81 (95% CI, 1.06-3.07). ORs varied little by maternal folic acid supplementation., Conclusions: Some folate pathway gene polymorphisms in the child or a parent may influence ALL risk. While biologically plausible, underlying mechanisms for these associations need further elucidation., Impact: Folate pathway polymorphisms may be related to risk of childhood ALL, but larger studies are needed for conclusive results., (©2014 American Association for Cancer Research.)

Purpose: To assess the risk of childhood central nervous system (CNS) tumors associated with parental occupational exposure to polycyclic aromatic hydrocarbons (PAH), diesel motor exhaust (DME), asbestos, crystalline silica, and metals, which are established carcinogens in adults., Methods: We pooled data from three population-based case-control studies from Germany, France, and the UK. Cases were children aged up to 15 years and diagnosed with CNS tumor, and controls were frequency-matched by age and sex. Socio-demographic data and parental occupation around conception/pregnancy and at diagnosis were collected using standardized interviews, face-to-face or by telephone. A general population job-exposure matrix was used to assign a level of exposure to each job. Logistic regression models were fitted to compute odds ratios and 95 % confidence intervals., Results: Our study included 1,361 cases of CNS tumors and 5,500 controls. Paternal exposure to PAH, asbestos, and metals around conception was associated with an increased moderate risk of CNS tumors, although statistically non-significant. The association with exposure to asbestos around conception and diagnosis was stronger when fathers were exposed to high levels. Paternal exposure to DME and silica, and maternal exposure to PAH, DME, asbestos, silica, and metals, were not associated with an increased risk of CNS tumors., Conclusion: Our large pooled study showed weak evidence of a modest association between paternal occupational exposure to PAH and CNS tumor risk. Our findings need further exploration in the future studies.

Purpose: We investigated whether paternal dietary intake of folate before conception is associated with the risk of childhood acute lymphoblastic leukemia (ALL) in a nationwide case-control study., Methods: Data on dietary folate intake during the 6 months before the child's conception were collected from 285 case fathers and 595 control fathers using a dietary questionnaire. Nutrient intake was quantified using a customized computer software package based on Australian food composition databases. Data on folate intake were analyzed using unconditional logistic regression, adjusting for study-matching variables, total energy, and potentially confounding variables. In a subset of 229 cases and 420 controls, data on vitamin B6 and vitamin B12 intake were also analyzed., Results: No consistent associations were seen with paternal dietary intake of folate or vitamin B6. Higher levels of paternal dietary vitamin B12 were appeared to be associated with an increased risk of childhood ALL, with those in the highest tertile of consumption having an OR of 1.51 (0.97, 2.36). The use of supplements containing folate and vitamins B6 or B12 was rare., Conclusions: We did not find any biologically plausible evidence that paternal nutrition in the period leading up to conception was associated with childhood ALL. Our finding for vitamin B12 may be a chance finding, given the number of analyses performed, or be attributable to participation bias because parents with a tertiary education had the lowest level of B12 intake and tertiary education was more common among control than case parents.

Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms., (© 2014 UICC.)