Geraldine P. Mineau

Intergenerational transmission of relative fertility and life course patterns

The direct relationship between fertility and fertility behavior of mothers and daughters was examined. It was hypothesized that the relative propensity to control family sizes in 1 generation is transmitted to the following generation and that transmission of fertility levels across generations is in part a result of the transmission of specific fertility-determining life-course behaviors across generations. The data were derived from the Mormon Historical Demography projects set of computerized family geneologies. To assess the importance of cohort effects the completed fertility of 1st daughters and last daughters was compared by mothers completed family size and mothers birth cohort. Daughters who were the last born tended to have lower fertility than 1st born daughters. For 1st born daughters a positive association between mothers and daughters family size was confirmed. The distribution of mothers and daughters relative to the median births for their respective cohorts was examined. Each woman was allocated to 1 of 3 groups: low -- completed fertility was 2 or more children less than the median for all women in the birth cohort; medium -- completed fertility was equal to + or - 1 child from the median for other women in the same birth cohort; and high -- completed fertility was 2 or more children greater than the median for all women in the birth cohort. It was expected that a greater proportion of daughters than mothers would have relatively low fertility. For the 1830-39 cohort only 15% of the mothers had relatively low fertility but 25% of their daughters did; for other mother cohorts the comparisons were 15:26 18:26 and 15:23. It also was expected that the daughters of low fertility mothers would be more likely to have relatively low fertility. For low fertility mothers in the 1830-39 cohort 33% of daughters had relatively low fertility; 24% fell in the relatively high fertility group. The expected difference was found for the 1840-49 cohort of mothers and for the 1860-69 cohort but not for the 1850-59 cohort. It also was expected that the daughters of relatively high fertility mothers would have relatively high fertility. 33% of daughters with high fertility mothers in the 1st cohort had relatively high fertility; only 23% had low fertility. This pattern was consistent for each of the other cohorts of mothers. Tabular and multivariate analyses supported the strong possibility that both fertility behavior and indirect associations regarding timing of fertility-related life course events were transmitted intergenerationally. Cohort-specific influences were substantial. The analyses confirmed both the hypothesized intergenerational fertility association and the hypothesized cohort-specific effects.

Fertility and post‐reproductive longevity

Abstract We examine the effects of reproduction on longevity among mothers and fathers after age 60. This study is motivated by evolutionary theories of aging and theories predicting social benefits and costs of children to older parents. We use the Utah Population Database, that includes a large genealogical database from the Utah Family History Library. Cox proportional hazard models based on 13,987 couples married between 1860–1899 indicate that women with fewer children as well as those bearing children late in life live longer post‐reproductive lives. As the burdens of motherhood increase, the relative gains in longevity of late fertile women increase compared to their non‐late fertile counterparts. Husbands’ longevity is less sensitive to reproductive history, although husbands have effects that are similar to those of their wives during the latter marriage cohort. We find some support for predictions based on evolutionary principles, but we also find evidence that implicates a role for shared marital environments.

The fall in incidence of prostate carcinoma : On the down side of a prostate specific antigen induced peak in incidence : Data from the Utah cancer registry

In the 1980s, prostate specific antigen (PSA) came into wide use as a prostate carcinoma screening and detection method in the United States. Following the introduction of PSA, the age‐adjusted incidence of prostate carcinoma reported by the Surveillance, Epidemiology, and End Results (SEER) program in the United States rose rapidly (from 84.4/100,000 in 1984 to 163/100,000 in 1991). When an increase in incidence is observed following the introduction of a screening method, a subsequent decrease in incidence may be expected as prevalent cases are removed from the population (a cull effect). Incidence rates may also fall due to factors such as decreased intensity of screening. The Utah Cancer Registry data were examined for a decrease in prostate cancer incidence.

Biomedical databases: protecting privacy and promoting research

When combined with medical information, large electronic databases of information that identify individuals provide superlative resources for genetic, epidemiology and other biomedical research. Such research resources increasingly need to balance the protection of privacy and confidentiality with the promotion of research. Models that do not allow the use of such individual-identifying information constrain research; models that involve commercial interests raise concerns about what type of access is acceptable. Researchers, individuals representing the public interest and those developing regulatory guidelines must be involved in an ongoing dialogue to identify practical models.

Effects of childhood and middle-adulthood family conditions on later-life mortality: evidence from the Utah Population Database, 1850-2002.

We examine how key early family circumstances affect mortality risks decades later. Early-life conditions are measured by parental mortality, parental fertility (e.g., offspring sibship size, parental age at offspring birth), religious upbringing, and parental socioeconomic status. Prior to these early-life conditions are familial and genetic factors that affect life span. Accordingly, we consider the role of parental and familial longevity on adult mortality risks. We analyze the large Utah Population Database which contains a vast amount of genealogical and other vital/health data that contain full life histories of individuals and hundreds of their relatives. To control for unobserved heterogeneity, we analyze sib-pair data for 12,000 sib-pairs using frailty models. We found modest effects of key childhood conditions (birth order, sibship size, parental religiosity, parental SES, and parental death in childhood). Our measures of familial aggregation of longevity were large and suggest an alternative view of early-life conditions.

Population-Based Analysis of Prognostic Factors and Survival in Familial Melanoma

PURPOSE Familial melanoma patients are reported to present with thinner melanomas, to be younger at the time of diagnosis, and to have a greater likelihood of developing multiple primary tumors. We sought to determine whether melanomas that occur in a familial setting demonstrate different prognostic and survival statistics relative to sporadic melanoma. PATIENTS AND METHODS This population-based study used the Utah Cancer Registry and Utah Population Database to objectively evaluate prognostic and survival statistics of the familial melanoma population. From 1973 to 1999, there were 7,785 cases of invasive melanoma identified through the Utah Cancer Registry. These were linked to the Utah Population Database, resulting in 2,659 subjects with family-history information from which a familiality score could be calculated. Cases scored in the top ninth percentile were assigned as high familial risk, and the remaining 91% were considered low familial risk. RESULTS Multivariate logistic-regression analysis found no association between sex, Breslow depth, Clark level, or survival and the familial status. Age at first diagnosis of invasive melanoma was slightly lower in the high-familial-risk group (57 v 60 years; P = .03). High-familial-risk subjects had more melanomas diagnosed at age 30 or younger (12% v 6%; P < .001). A significant difference in the overall number of individuals with two or more primary malignant melanomas was not detected among the groups (P = .2). CONCLUSION These data suggest that melanomas occurring in the context of an underlying inherited susceptibility do not have a significantly different biologic behavior.

Familial predisposition to developmental dysplasia of the hip.

Background Developmental dysplasia of the hip (DDH) is a common birth defect and is thought to have genetic contributions to the phenotype. It is likely that DDH is genetically heterogeneous with environmental modifiers. The Utah Population Database (UPDB) is a computerized integration of pedigrees, vital statistics, and medical records representing over 6 million individuals, and is a unique resource providing the ability to search for familial factors beyond the nuclear family, decreasing the effect of a shared environment. The purpose of this study is to assess the degree of relationship between individuals with DDH. Methods Datasets were created from UPDB statewide birth certificates and from the University of Utah Health Sciences Center enterprise data warehouse using records for DDH and linked to the UPDB. Controls for the dataset were selected that matched cases on birth year and sex and 10 controls were selected per case. Statistics computed for each family were the number of descendants, the observed number of affected, the expected number of affected, P value, familial standardize incidence ratio, relative risks (RRs), and standard error. A kinship analysis tool was used to find pedigrees with excess DDH. Results The combined data resulted in 1649 distinct individuals with DDH. RR was significantly increased in first-degree relatives (RR=12.1; P<0.000001), siblings (RR=11.9; P<0.000001) and first cousins (RR=1.7; P=0.04). A total of 468 families were identified with at least 5 affected individuals in a family. These results were then filtered to only contain families that had a P value of less than 0.01. This resulted in 141 founders with anywhere between 4 and 30 affected living descendants with a P value of less than 0.01 with family sizes ranging from 594 to 44,819 descendants. A total of 28 founders had a familial standardize incidence ratio of greater than 5.0. Conclusions These data suggest a genetic contribution to DDH with a 12-fold increase in risk for first-degree relatives. Better phenotypic characterization and classification will be critical for future genetic analyses. Level of Evidence Prognostic level II.

Historical trends of survival among widows and widowers

One of the most consistent findings in social demography is that recently widowed individuals, male or female, have higher rates of mortality than comparable married persons. These results are based generally on contemporary studies in developed nations where life expectancy is high. Because of data limitations, there are few studies available to determine whether these findings also occur when mortality rates were higher. This study uses the Utah Population Database that was developed from extensive family genealogies and now linked to Utah death certificates. These data make it possible to employ life course analysis of four marriage cohorts extending from 1860 through 1904 with mortality follow-up to 1990. This approach is used to compare mortality risks of widowed males and females relative to comparable married individuals. Covariates included in the study are remarriage, as well as religion and number of children ever born; these are all hypothesized to have protective effects on mortality risks for widowed men and women. Analysis of these data indicates that there are significant differences in the mortality risk for widowed men and women, and it is widowed men who have an excess risk of dying in every cohort and nearly every age. A consistent pattern of excess mortality in the comparison of married and widowed women was not observed. There are significant female and male differences in the effect of religion which was treated as a proxy for life style and social support: however, remarriage as a proxy for social support has similar protective effects on the surviving spouse.

Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis.

OBJECTIVE To compare birth outcomes among female survivors of childhood and adolescent cancer who subsequently bear children, relative to those of women without a history of cancer. DESIGN Retrospective cohort study. SETTING Four US regions. PARTICIPANTS Cancer registries identified girls younger than 20 years who were diagnosed as having cancer from 1973 through 2000. Linked birth records identified the first live births after diagnosis (n = 1898). Comparison subjects were selected from birth records (n = 14 278). Survivors of genital tract carcinomas underwent separate analysis. MAIN EXPOSURE Cancer diagnosis at younger than 20 years. MAIN OUTCOME MEASURES Infant low birth weight, preterm delivery, sex ratio, malformations, mortality, and delivery method, and maternal diabetes, anemia, and preeclampsia. RESULTS Infants born to childhood cancer survivors were more likely to be preterm (relative risk [RR], 1.54; 95% confidence interval [CI], 1.30-1.83) and to weigh less than 2500 g (1.31; 1.10-1.57). For the offspring of genital tract carcinoma survivors, RRs were 1.33 (95% CI, 1.13-1.56) and 1.29 (1.10-1.53), respectively. There were no increased risks of malformations, infant death, or altered sex ratio, suggesting no increased germ cell mutagenicity. In exploratory analysis, bone cancer survivors had an increased risk of diabetes (RR, 4.92; 95% CI, 1.60-15.13), and anemia was more common among brain tumor survivors (3.05; 1.16-7.98) and childhood cancer survivors whose initial treatment was chemotherapy only (2.45; 1.16-5.17). CONCLUSIONS Infants born to female survivors of childhood and adolescent cancer were not at increased risk of malformations or death. Increased occurrence of preterm delivery and low birth weight suggest that close monitoring is warranted. Increased diabetes and anemia among subgroups have not been reported, suggesting areas for study.

Effects of BRCA1 and BRCA2 mutations on female fertility

Women with BRCA1/2 mutations have a significantly higher lifetime risk of developing breast or ovarian cancer. We suggest that female mutation carriers may have improved fitness owing to enhanced fertility relative to non-carriers. Here we show that women who are carriers of BRCA1/2 mutations living in natural fertility conditions have excess fertility as well as excess post-reproductive mortality in relation to controls. Individuals who tested positive for BRCA1/2 mutations who linked into multi-generational pedigrees within the Utah Population Database were used to identify putative obligate carriers. We find that women born before 1930 who are mutation carriers have significantly more children than controls and have excess post-reproductive mortality risks. They also have shorter birth intervals and end child-bearing later than controls. For contemporary women tested directly for BRCA1/2 mutations, an era when modern contraceptives are available, differences in fertility and mortality persist but are attenuated. Our findings suggest the need to re-examine the wider role played by BRCA1/2 mutations. Elevated fertility of female mutation carriers indicates that they are more fecund despite their elevated post-reproductive mortality risks.