Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

BACKGROUND AND AIMS: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. APPROACH AND RESULTS: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. CONCLUSIONS: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Gestational age at birth and type 1 diabetes in childhood and young adulthood: a nationwide register study in Finland, Norway and Sweden.

AIMS/HYPOTHESIS: Children and adults born preterm have an increased risk of type 1 diabetes. However, there is limited information on risk patterns across the full range of gestational ages, especially after extremely preterm birth (23-27 weeks of gestation). We investigated the risk of type 1 diabetes in childhood and young adulthood across the full range of length of gestation at birth. METHODS: Data were obtained from national registers in Finland, Norway and Sweden. In each country, information on study participants and gestational age was collected from the Medical Birth Registers, information on type 1 diabetes diagnoses was collected from the National Patient Registers, and information on education, emigration and death was collected from the respective national register sources. Individual-level data were linked using unique personal identity codes. The study population included all individuals born alive between 1987 and 2016 to mothers whose country of birth was the respective Nordic country. Individuals were followed until diagnosis of type 1 diabetes, death, emigration or end of follow-up (31 December 2016 in Finland, 31 December 2017 in Norway and Sweden). Gestational age was categorised as extremely preterm (23-27 completed weeks), very preterm (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks), early term (37-38 weeks), full term (39-41 weeks; reference) and post term (42-45 weeks). HRs and 95% CIs from country-specific covariate-adjusted Cox regression models were combined in a meta-analysis using a common-effect inverse-variance model. RESULTS: Among 5,501,276 individuals, 0.2% were born extremely preterm, 0.5% very preterm, 0.7% moderately preterm, 4.2% late preterm, 17.7% early term, 69.9% full term, and 6.7% post term. A type 1 diabetes diagnosis was recorded in 12,326 (0.8%), 6364 (0.5%) and 16,856 (0.7%) individuals at a median age of 8.2, 13.0 and 10.5 years in Finland, Norway and Sweden, respectively. Individuals born late preterm or early term had an increased risk of type 1 diabetes compared with their full-term-born peers (pooled, multiple confounder-adjusted HR 1.12, 95% CI 1.07, 1.18; and 1.15, 95% CI 1.11, 1.18, respectively). However, those born extremely preterm or very preterm had a decreased risk of type 1 diabetes (adjusted HR 0.63, 95% CI 0.45, 0.88; and 0.78, 95% CI 0.67, 0.92, respectively). These associations were similar across all three countries. CONCLUSIONS/INTERPRETATION: Individuals born late preterm and early term have an increased risk of type 1 diabetes while individuals born extremely preterm or very preterm have a decreased risk of type 1 diabetes compared with those born full term.

Female reproductive histories and the risk of chronic obstructive pulmonary disease.

BACKGROUND: Female reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess whether age at menarche, number of children, infertility, miscarriage, stillbirth and age at natural menopause were associated with the risk of COPD. METHODS: Women from three cohorts with data on reproductive factors, COPD and covariates were included. Cause specific Cox regression models were adjusted for birth year, race, educational level, body mass index and pack years of smoking, stratified by asthma, and incorporating interaction between birth year and time. Between cohort differences and within cohort correlations were taken into account. RESULTS: Overall, 2 83 070 women were included and 10 737 (3.8%) developed COPD after a median follow-up of 11 (IQR 10-12) years. Analyses revealed a U shaped association between age at menarche and COPD (≤11 vs 13: HR 1.17, 95% CI 1.11 to 1.23; ≥16 vs 13: HR 1.24, 95% CI 1.21 to 1.27). Women with three or more children (3 vs 2: HR 1.14, 95% CI 1.12 to 1.17; ≥4 vs 2: HR 1.34, 95% CI 1.28 to 1.40), multiple miscarriages (2 vs 0: HR 1.28, 95% CI 1.24 to 1.32; ≥3 vs 0: HR 1.36, 95% CI 1.30 to 1.43) or stillbirth (1 vs 0: HR 1.38, 95% CI 1.25 to 1.53; ≥2 vs 0: HR 1.67, 95% CI 1.32 to 2.10) were at a higher risk of COPD. Among postmenopausal women, earlier age at natural menopause was associated with an increased risk of COPD (<40 vs 50-51: HR 1.69, 95% CI 1.63 to 1.75; 40-44 vs 50-51: HR 1.42, 95% CI 1.38 to 1.47). CONCLUSIONS: Multiple female reproductive factors, including age at menarche, number of children, miscarriage, stillbirth, and age at natural menopause were associated with the risk of COPD.

Preterm delivery and maternal obesity remain common complications in pregnancies with type 1 diabetes-A nationwide study in Sweden.

AIM: A primary goal of obstetric care of women with type 1 diabetes (T1D) is to reduce the risks of preterm birth (PTB). Besides hyperglycaemia, maternal obesity is an important risk factor for PTB in T1D. However, it's unclear if public health efforts decreased risks of maternal obesity and PTB in pregnancies with T1D. We examined time-trends over the last 20 years in the distribution of gestational ages at birth (GA) in offspring of women with T1D in Sweden, and in maternal BMI in the same mothers. METHODS: Population-based cohort study, using data from national registries in Sweden. To capture differences not only in the median values, we used quantile regression models to compare the whole distributions of GA's and early pregnancy BMI between deliveries in 1998-2007 (P1) and 2008-2016 (P2). Multivariable models were adjusted for differences in maternal age, smoking and education between periods 1 and 2. RESULTS: The study included 7639 offspring of women with T1D between 1998 and 2016. The 10% percentile GA, increased with 0.09 days (95% CI: -0.11 to 0.35) between P1 and P2. The 90% percentile for BMI was 1.20 kg/m2 higher (95% CI: 0.57 to 1.83) in P2. Risks of PTB remained stable over time also when adjusting for maternal BMI. CONCLUSION: Despite modern diabetes management, the distribution of GA, and consequently the risk of PTB in T1D, remained unchanged from 1998 to 2016. During the same time, maternal BMI increased, particularly in the already obese.

Association of infertility and recurrent pregnancy loss with the risk of dementia.

Emerging evidence has shown the association between female reproductive histories (e.g., menarche age, parity, premature and early menopause) and the risk of dementia. However, little attention has been given to infertility and pregnancy loss. To examine the associations of infertility, recurrent miscarriages, and stillbirth with the risk of dementia, this study used data from four cohorts in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events. Women with data on at least one of the reproductive exposures of interest, dementia, and all covariates were included. Histories of infertility, miscarriage, and stillbirth were self-reported. Dementia (including Alzheimer's disease) was identified through surveys, aged care, pharmaceutical, hospital, and death registry data. Cause-specific Cox regression models were used to estimate the hazard ratios of dementia, accounting for well-established risk factors of dementia, study variability, and within-study correlation. Overall, 291,055 women were included at a median (interquartile range) age of 55.0 (47.0-62.0) at baseline. During the median (interquartile range) follow-up period of 13.0 (12.0-14.0) years, 3334 (1.2%) women developed dementia. Compared to women without stillbirth, a history of recurrent stillbirths (≥ 2) was associated with 64% higher risk of dementia (adjusted hazard ratio = 1.64, 95% confidence interval: 1.46-1.85). Compared to women without miscarriage, women with recurrent miscarriages (≥ 3) were at 22% higher risk of dementia (adjusted hazard ratio = 1.22, 95% confidence interval: 1.19-1.25). These findings suggest that recurrent stillbirths is a risk factor for dementia and may need to be considered in risk assessment of dementia in women.

Paternal and maternal psychiatric history and risk of preterm and early term birth: A nationwide study using Swedish registers.

BACKGROUND: Women with psychiatric diagnoses are at increased risk of preterm birth (PTB), with potential life-long impact on offspring health. Less is known about the risk of PTB in offspring of fathers with psychiatric diagnoses, and for couples where both parents were diagnosed. In a nationwide birth cohort, we examined the association between psychiatric history in fathers, mothers, and both parents and gestational age. METHODS AND FINDINGS: We included all infants live-born to Nordic parents in 1997 to 2016 in Sweden. Psychiatric diagnoses were obtained from the National Patient Register. Data on gestational age were retrieved from the Medical Birth Register. Associations between parental psychiatric history and PTB were quantified by relative risk (RR) and two-sided 95% confidence intervals (CIs) from log-binomial regressions, by psychiatric disorders overall and by diagnostic categories. We extended the analysis beyond PTB by calculating risks over the whole distribution of gestational age, including "early term" (37 to 38 weeks). Among the 1,488,920 infants born throughout the study period, 1,268,507 were born to parents without a psychiatric diagnosis, of whom 73,094 (5.8%) were born preterm. 4,597 of 73,500 (6.3%) infants were born preterm to fathers with a psychiatric diagnosis, 8,917 of 122,611 (7.3%) infants were born preterm to mothers with a pscyhiatric diagnosis, and 2,026 of 24,302 (8.3%) infants were born preterm to both parents with a pscyhiatric diagnosis. We observed a shift towards earlier gestational age in offspring of parents with psychiatric history. The risks of PTB associated with paternal and maternal psychiatric diagnoses were similar for different psychiatric disorders. The risks for PTB were estimated at RR 1.12 (95% CI [1.08, 1.15] p < 0.001) for paternal diagnoses, at RR 1.31 (95% CI [1.28, 1.34] p < 0.001) for maternal diagnoses, and at RR 1.52 (95% CI [1.46, 1.59] p < 0.001) when both parents were diagnosed with any psychiatric disorder, compared to when neither parent had a psychiatric diagnosis. Stress-related disorders were associated with the highest risks of PTB with corresponding RRs estimated at 1.23 (95% CI [1.16, 1.31] p < 0.001) for a psychiatry history in fathers, at 1.47 (95% CI [1.42, 1.53] p < 0.001) for mothers, and at 1.90 (95% CI [1.64, 2.20] p < 0.001) for both parents. The risks for early term were similar to PTB. Co-occurring diagnoses from different diagnostic categories increased risk; for fathers: RR 1.10 (95% CI [1.07, 1.13] p < 0.001), 1.15 (95% CI [1.09, 1.21] p < 0.001), and 1.33 (95% CI [1.23, 1.43] p < 0.001), for diagnoses in 1, 2, and ≥3 categories; for mothers: RR 1.25 (95% CI [1.22, 1.28] p < 0.001), 1.39 (95% CI [1.34, 1.44] p < 0.001) and 1.65 (95% CI [1.56, 1.74] p < 0.001). Despite the large sample size, statistical precision was limited in subgroups, mainly where both parents had specific psychiatric subtypes. Pathophysiology and genetics underlying different psychiatric diagnoses can be heterogeneous. CONCLUSIONS: Paternal and maternal psychiatric history were associated with a shift to earlier gestational age and increased risk of births before full term. The risk consistently increased when fathers had a positive history of different psychiatric disorders, increased further when mothers were diagnosed and was highest when both parents were diagnosed.

Hypertensive conditions of pregnancy, preterm birth, and premenopausal breast cancer risk: a premenopausal breast cancer collaborative group analysis.

PURPOSE: Women with preeclampsia are more likely to deliver preterm. Reports of inverse associations between preeclampsia and breast cancer risk, and positive associations between preterm birth and breast cancer risk are difficult to reconcile. We investigated the co-occurrence of preeclampsia/gestational hypertension with preterm birth and breast cancer risk using data from the Premenopausal Breast Cancer Collaborative Group. METHODS: Across 6 cohorts, 3096 premenopausal breast cancers were diagnosed among 184,866 parous women. We estimated multivariable hazard ratios (HR) and 95% confidence intervals (CI) for premenopausal breast cancer risk using Cox proportional hazards regression. RESULTS: Overall, preterm birth was not associated (HR 1.02, 95% CI 0.92, 1.14), and preeclampsia was inversely associated (HR 0.86, 95% CI 0.76, 0.99), with premenopausal breast cancer risk. In stratified analyses using data from 3 cohorts, preterm birth associations with breast cancer risk were modified by hypertensive conditions in first pregnancies (P-interaction = 0.09). Preterm birth was positively associated with premenopausal breast cancer in strata of women with preeclampsia or gestational hypertension (HR 1.52, 95% CI: 1.06, 2.18), but not among women with normotensive pregnancy (HR = 1.09, 95% CI: 0.93, 1.28). When stratified by preterm birth, the inverse association with preeclampsia was more apparent, but not statistically different (P-interaction = 0.2), among women who did not deliver preterm (HR = 0.82, 95% CI 0.68, 1.00) than those who did (HR = 1.07, 95% CI 0.73, 1.56). CONCLUSION: Findings support an overall inverse association of preeclampsia history with premenopausal breast cancer risk. Estimates for preterm birth and breast cancer may vary according to other conditions of pregnancy.

Direct additive genetics and maternal effect contribute to the risk of Tourette disorder.

BACKGROUND: Risk for Tourette disorder, and chronic motor or vocal tic disorders (referenced here inclusively as CTD), arise from a combination of genetic and environmental factors. While multiple studies have demonstrated the importance of direct additive genetic variation for CTD risk, little is known about the role of cross-generational transmission of genetic risk, such as maternal effect, which is not transmitted via the inherited parental genomes. Here, we partition sources of variation on CTD risk into direct additive genetic effect (narrow-sense heritability) and maternal effect. METHODS: The study population consists of 2 522 677 individuals from the Swedish Medical Birth Register, who were born in Sweden between 1 January 1973 and 31 December 2000, and followed for a diagnosis of CTD through 31 December, 2013. We used generalised linear mixed models to partition the liability of CTD into: direct additive genetic effect, genetic maternal effect and environmental maternal effect. RESULTS: We identified 6227 (0.2%) individuals in the birth cohort with a CTD diagnosis. A study of half-siblings showed that maternal half-siblings had twice higher risk of developing a CTD compared with paternal ones. We estimated 60.7% direct additive genetic effect (95% credible interval, 58.5% to 62.4%), 4.8% genetic maternal effect (95% credible interval, 4.4% to 5.1%) and 0.5% environmental maternal effect (95% credible interval, 0.2% to 7%). CONCLUSIONS: Our results demonstrate genetic maternal effect contributes to the risk of CTD. Failure to account for maternal effect results in an incomplete understanding of the genetic risk architecture of CTD, as the risk for CTD is impacted by maternal effect which is above and beyond the risk from transmitted genetic effect.

Familial clustering of psychiatric disorders and low IQ.

BACKGROUND: Although the ICD and DSM differentiate between different psychiatric disorders, these often share symptoms, risk factors, and treatments. This was a population-based, case-control, sibling study examining familial clustering of all psychiatric disorders and low IQ, using data from the Israel Draft-Board Registry on all Jewish adolescents assessed between 1998 and 2014. METHODS: We identified all cases with autism spectrum disorder (ASD, N = 2128), severe intellectual disability (ID, N = 9572), attention-deficit hyperactive disorder (ADHD) (N = 3272), psychotic (N = 7902), mood (N = 9704), anxiety (N = 10 606), personality (N = 24 816), or substance/alcohol abuse (N = 791) disorders, and low IQ (⩾2 SDs below the population mean, N = 31 186). Non-CNS control disorders were adolescents with Type-1 diabetes (N = 2427), hernia (N = 29 558) or hematological malignancies (N = 931). Each case was matched with 10 age-matched controls selected at random from the Draft-Board Registry, with replacement, and for each case and matched controls, we ascertained all full siblings. The main outcome measure was the relative recurrence risk (RRR) of the sibling of a case having the same (within-disorder RRR) or a different (across-disorder RRR) disorder. RESULTS: Within-disorder RRRs were increased for all diagnostic categories, ranging from 11.53 [95% confidence interval (CI): 9.23-14.40] for ASD to 2.93 (95% CI: 2.80-3.07) for personality disorders. The median across-disorder RRR between any pair of psychiatric disorders was 2.16 (95% CI: 1.45-2.43); the median RRR between low IQ and any psychiatric disorder was 1.37 (95% CI: 0.93-1.98). There was no consistent increase in across-disorder RRRs between the non-CNS disorders and psychiatric disorders and/or low IQ. CONCLUSION: These large population-based study findings suggest shared etiologies among most psychiatric disorders, and low IQ.

Maternal rheumatoid arthritis and risk of autism in the offspring.

BACKGROUND: Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. METHODS: We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity. RESULTS: Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11-1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12-2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24-1.60). CONCLUSIONS: In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.