1. Time dimension: Age “The ripples of adolescent motherhood: social, educational, and medical outcomes for children of teen and prior teen mothers.” https://www.ncbi.nlm.nih.gov/pubmed/20674531
Research Question: This study, in contrast, presents evidence suggesting that the problems associated with teen motherhood have been substantially underestimated. We expand current knowledge on the effect of teen motherhood in several important ways. First, we examined the outcomes experienced by these children across multiple domains (medical, educational, and social). Second, we reviewed long-term consequences throughout childhood and into early adulthood. Third, we evaluated outcomes experienced by the later children of teen mothers—identifying those born to older mothers with a history of teen birth as children of prior teen mothers. Finally, by using rich population-wide data, we explored the societal-level consequences of teen motherhood.
Study Sample: This was a retrospective cohort study examining all children residing in the city of Winnipeg (population 620 000) at age 17 years who were born and raised in Manitoba. Six cohorts covering all children born 1979–1982 and 1984– 1985 were analyzed.
Longitudinal design: Retrospective cohort study
Analysis approach: Child health status was measured by: 1) mortality, 2) hospitalization (excluding birth hospitalization and admissions for pregnancy/childbirth), and 3) being among the top 10% of hospital day users (total days). These health measures were examined over 3 time periods: infancy (infancy (<1yr), toddler/preschool (1-5 years), and school age/adolescence 6-17 years). Markers of educational achievement included: 1) mean course marks in ninth grade, and 2) successful high school graduation within 6 years of entering ninth grade. Social outcomes included: 1) whether or not the child was taken into foster care at any point from age 8–17 years (ages for which these data were available), 2) the child’s family was monitored by Child and Family Services (typically at the request of the physician or another agency) at some point from age 8–17 years, 3) the child received income assistance at some time as a young adult (age 18 to 25 years), and 4) the female child became a teen mother herself. The education, foster care, and Child and Family Services outcomes were available for only the 1984 and 1985 birth cohorts. Multivariate regression analyses were used to adjust for likely confounders in several categories.
2. Time dimension: time since study enrollment “Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women’s Health Initiative Randomized Trial”
https://www.ncbi.nlm.nih.gov/pubmed/26668177
Research Question: In the current report, we extend that finding by providing analyses on estrogen plus progestin effects on endometrial cancer type, findings in relevant clinical subgroups, and information on endometrial cancer–related mortality
Study Sample: Briefly, postmenopausal women age 50 to 79 years with an intact uterus were enrolled at 40 US clinical centers. Exclusions were prior breast cancer, anticipated survival of less than 3 years, and previous invasive cancer within 10 years. A three-month wash-out period was required for hormone therapy users at screening.
Longitudinal design: Prospective cohort. “After 5.6 years of median follow-up, the intervention was stopped when overall risks exceeded benefits and participants were instructed to discontinue study drug on July 8, 2002 (16). Protocol-defined follow-up continued through March 31, 2005, the prospectively determined trial completion date. Follow-up after that date required reconsent, obtained from 12 788 (83%) of 15 408 surviving participants.”
Analysis approach: Results for endometrial cancer incidence and deaths directly attributed to endometrial cancer were assessed with time-to-event methods based on the intent-to-treat principle, which included all 16 608 randomly assigned participants. Cancer incidence rate comparisons, presented as hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox proportional hazard models, were stratified by age and randomization groups in the WHI dietary trial, and proportionality was verified with the Grambsch and Therneau’s test (19).
3. Another time dimension: duration of adult overweight “Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women’s Health Initiative: A Longitudinal Study from the United States”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4987008/pdf/pmed.1002081.pdf
Research Question: While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women.
Study Sample: The WHI is a large, multi-center prospective cohort study of postmenopausal women. In total, 93,676 women were enrolled in the observational study, and 68,132 were enrolled in the clinical trial arm (n = 161,808) [16]. For this study, we included all participants from the observational study cohort, except those who reported cancer prior to or at baseline or without data on cancer history (n = 12,827) and women with incomplete follow-up information (n = 411) (Fig 1).
Longitudinal design: Prospective cohort. Information on BMI for was obtained from retrospective self-reports at baseline for ages 18, 35, and 50 y, from weight and height measurements at baseline and at 3-y follow-up, and from self-reports at follow-up years 4–8. BMI was calculated by dividing weight in kilograms by height in meters squared. For inclusion in the study, women were required to have valid body weight information from at least three occasions and a valid baseline measurement of body weight and height.
Analysis approach: The analysis was carried out in two steps. In the first step, BMI was modeled across all ages using a quadratic growth model with random intercept and random slope, incorporating all Fig 1. Flowchart of participant inclusion. *Including data at baseline and excluding data from the year preceding cancer diagnosis; including BMI from self-reported as well as measured height and weight; BMI values lower 70 kg/m2 were excluded. doi:10.1371/journal.pmed.1002081.g001 Adulthood Overweight, Obesity, and Cancer Risk PLOS Medicine | DOI:10.1371/journal.pmed.1002081 August 16, 2016 5 / 16 available BMI information from all included participants [19]. No random coefficient was included for the quadratic term. Using this approach, we allowed individuals to have their own BMI trajectory. Using the full model, BMI was predicted from age 18 y until the age at study exit for every cohort member. In the second step of the analysis, Cox proportional hazard models with time since enrollment as the underlying time metric were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between BMI overweight/obesity duration, OWY/ OBY, and the risk of developing specific cancers. Overweight/obesity duration and OWY/OBY were treated as continuous, time-varying covariates.