Association between SARS-CoV-2 vaccination and healthcare contacts for menstrual disturbance and bleeding in women before and after menopause: nationwide, register based cohort study.

OBJECTIVES: To evaluate the risks of any menstrual disturbance and bleeding following SARS-CoV-2 vaccination in women who are premenopausal or postmenopausal. DESIGN: A nationwide, register based cohort study. SETTING: All inpatient and specialised outpatient care in Sweden from 27 December 2020 to 28 February 2022. A subset covering primary care for 40% of the Swedish female population was also included. PARTICIPANTS: 2 946 448 Swedish women aged 12-74 years were included. Pregnant women, women living in nursing homes, and women with history of any menstruation or bleeding disorders, breast cancer, cancer of female genital organs, or who underwent a hysterectomy between 1 January 2015 and 26 December 2020 were excluded. INTERVENTIONS: SARS-CoV-2 vaccination, by vaccine product (BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 (AZD1222)) and dose (unvaccinated and first, second, and third dose) over two time windows (one to seven days, considered the control period, and 8-90 days). MAIN OUTCOME MEASURES: Healthcare contact (admission to hospital or visit) for menstrual disturbance or bleeding before or after menopause (diagnosed with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes N91, N92, N93, N95). RESULTS: 2 580 007 (87.6%) of 2 946 448 women received at least one SARS-CoV-2 vaccination and 1 652 472 (64.0%) 2 580 007 of vaccinated women received three doses before the end of follow-up. The highest risks for bleeding in women who were postmenopausal were observed after the third dose, in the one to seven days risk window (hazard ratio 1.28 (95% confidence interval 1.01 to 1.62)) and in the 8-90 days risk window (1.25 (1.04 to 1.50)). The impact of adjustment for covariates was modest. Risk of postmenopausal bleeding suggested a 23-33% increased risk after 8-90 days with BNT162b2 and mRNA-1273 after the third dose, but the association with ChAdOx1 nCoV-19 was less clear. For menstrual disturbance or bleeding in women who were premenopausal, adjustment for covariates almost completely removed the weak associations noted in the crude analyses. CONCLUSIONS: Weak and inconsistent associations were observed between SARS-CoV-2 vaccination and healthcare contacts for bleeding in women who are postmenopausal, and even less evidence was recorded of an association for menstrual disturbance or bleeding in women who were premenopausal. These findings do not provide substantial support for a causal association between SARS-CoV-2 vaccination and healthcare contacts related to menstrual or bleeding disorders.

Impact of BMI and smoking in adolescence and at the start of pregnancy on birth weight.

BACKGROUND: Birth weight is an indicator of intra-uterine conditions but also a determinant for future health. The importance of preconception health for a healthy birth weight has been emphasized, but evidence is lacking on how modifiable factors in adolescence, such as body mass index (BMI) and smoking, affect future pregnancy outcome. We evaluated associations between BMI and smoking in adolescence and at the start of pregnancy and birth weight of the first-born child. METHODS: This longitudinal study included 1256 mothers, born 1962-1992, and their first-born children, born between 1982-2016. Self-reported questionnaire information on weight, height and smoking at age 19 was cross-linked with national register data obtained at the start of pregnancy and with the birth weights of the children. Univariable and multivariable linear regressions were performed to determine the impact of maternal factors at 19 years of age and at the start of the pregnancy respectively, and the importance of BMI status at these points of time for the birth weight of the first child. RESULTS: BMI and smoking at the start of the pregnancy displayed strong associations with birth weight in a multivariable analysis, BMI with a positive association of 14.9 g per BMI unit (95% CI 6.0; 23.8 p = 0.001) and smoking with a negative association of 180.5 g (95% CI -275.7; -85.4) p = 0.0002). Smoking and BMI at 19 years of age did not show this association. Maternal birth weight showed significant associations in models at both time-points. Becoming overweight between age 19 and the start of the pregnancy was associated with a significantly higher birth weight (144.6 (95% CI 70.7;218.5) p = 0.0002) compared to mothers with normal weight at both time points. CONCLUSIONS: Our findings indicate that the time period between adolescence and first pregnancy could be a window of opportunity for targeted health promotion to prevent intergenerational transmission of obesity.

Timing of the Pubertal Growth Spurt and Prostate Cancer.

Previous studies of pubertal timing and the risk of prostate cancer have used self-reported markers of pubertal development, recalled in mid-life, and the results have been inconclusive. Our aim was to evaluate the age at the pubertal growth spurt, an objective marker of pubertal timing, and the risk of prostate cancer and high-risk prostate cancer. This population-based cohort study included 31,971 men with sufficient height measurements to calculate age at peak height velocity (PHV). Outcomes were accessed through national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions with follow up starting at 20 years of age. In total, 1759 cases of prostate cancer including 449 high-risk were diagnosed during follow up. Mean follow up was 42 years (standard deviation 10.0). Compared to quintiles 2-4 (Q2-4), men in the highest age at PHV quintile (Q5) had lower risk of prostate cancer (HR 0.83, 95% CI 0.73-0.94), and of high-risk prostate cancer (0.73; 0.56-0.94). In an exploratory analysis with follow up starting at age at PHV, late pubertal timing was no longer associated with reduced risk of prostate cancer. Later pubertal timing was associated with reduced risk of prostate cancer and especially high-risk prostate cancer. We propose that the risk of prostate cancer might be influenced by the number of years with exposure to adult levels of sex steroids.

Childhood body mass index is associated with the risk of adult hematologic malignancies in men-The best Gothenburg cohort.

Hematologic malignancies are common and the incidence is increasing. Adult obesity has been associated with hematologic malignancies (HM), but the importance of body mass index (BMI) in childhood and during puberty has not been evaluated. The aim of the present study was to evaluate the relative contribution of BMI and height in childhood and during puberty for the risk of adult HM. 37 669 men born in 1946 to 1961 who had weight and height measured at 8 (childhood) and 20 (young adult age) years of age available from the BMI Epidemiology Study were included in the study. Pubertal BMI change was calculated as BMI at 20 years of age minus BMI at 8 years of age. Information on HM was retrieved from Swedish registers (459 cases of HM). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. Childhood BMI (HR 1.11 per SD increase [95% CI 1.02-1.23]), but not pubertal BMI change, was associated with hematologic malignancies in a linear manner. Childhood BMI was, independent of childhood height, associated with the diagnostic entities Non-Hodgkin lymphoma (HR 1.14 [95% CI 1.00-1.30]) and its largest subgroup diffuse large B-cell lymphoma (HR 1.31 [95% CI 1.03-1.67]). Childhood height was associated with multiple myeloma (HR 1.30 [95% CI 1.04-1.64]) independent of childhood BMI. We conclude that childhood but not puberty is the critical developmental period regarding future risk of HM and we suggest that elevated childhood BMI is a determinant of Non-Hodgkin lymphoma and diffuse large B-cell lymphoma.

Childhood Body Mass Index Is Associated with Risk of Adult Colon Cancer in Men: An Association Modulated by Pubertal Change in Body Mass Index.

BACKGROUND: The relative contribution of childhood and pubertal body mass index (BMI) for the risk of adult colorectal cancer is not known. The aim of this study was to evaluate the independent associations for childhood BMI and pubertal BMI change with risk of colorectal cancer in men. METHODS: We included 37,663 men born in 1946 to 1961 who had weight and height measured at 8 (childhood) and 20 (young adult age) years of age available from the BMI Epidemiology Study. Information on colorectal cancer was retrieved from the Swedish National Patient Register (257 cases of colon cancer and 159 cases of rectal cancer). RESULTS: Childhood BMI at 8 years of age [HR, 1.19 per SD increase; 95% confidence interval (CI), 1.06-1.33], but not pubertal BMI change (HR, 1.02; 95% CI, 0.90-1.15), was associated with increased risk of colon cancer. Due to a significant interaction between childhood BMI and pubertal BMI change (P < 0.001), we stratified the analyses according to the median of pubertal BMI change. Childhood BMI was associated with risk of colon cancer in individuals with a pubertal BMI change above, but not below, the median (above: HR = 1.48, 95% CI, 1.26-1.74; below: HR = 0.95, 95% CI, 0.80-1.12). Neither childhood BMI nor pubertal BMI change was associated with rectal cancer. CONCLUSIONS: High childhood BMI was associated with increased risk of colon cancer only if it was followed by a pubertal BMI increase above the median. IMPACT: Further studies should evaluate prepubertal childhood BMI in relation to pubertal BMI change and BMI in middle age for the risk of colon cancer.