Male infertility in long-term survivors of pediatric cancer: a report from the childhood cancer survivor study.

PURPOSE: The purpose of this study was to assess the prevalence of male infertility and treatment-related risk factors in childhood cancer survivors. METHODS: Within the Childhood Cancer Survivor Study, 1,622 survivors and 274 siblings completed the Male Health Questionnaire. The analysis was restricted to survivors (938/1,622; 57.8 %) and siblings (174/274; 63.5 %) who tried to become pregnant. Relative risks (RR) and 95 % confidence intervals (CI) for the prevalence of self-reported infertility were calculated using generalized linear models for demographic variables and treatment-related factors to account for correlation among survivors and siblings of the same family. All statistical tests were two-sided. RESULTS: Among those who provided self-report data, the prevalence of infertility was 46.0 % in survivors versus 17.5 % in siblings (RR = 2.64, 95 % CI 1.88-3.70, p < 0.001). Of survivors who met the definition for infertility, 37 % had reported at least one pregnancy with a female partner that resulted in a live birth. In a multivariable analysis, risk factors for infertility included an alkylating agent dose (AAD) score ≥3 (RR = 2.13, 95 % CI 1.69-2.68 for AAD ≥3 versus AAD <3), surgical excision of any organ of the genital tract (RR = 1.63, 95 % CI 1.20-2.21), testicular radiation ≥4 Gy (RR = 1.99, 95 % CI 1.52-2.61), and exposure to bleomycin (RR = 1.55, 95 % CI 1.20-2.01). CONCLUSION: Many survivors who experience infertility father their own children, suggesting episodes of both fertility and infertility. This and the novel association of infertility with bleomycin warrant further investigation. IMPLICATIONS FOR CANCER SURVIVORS: Though infertility is common, male survivors reporting infertility often father their own children. Bleomycin may pose some fertility risk.

Longevity of patients born with myelomeningocele.

There are limited data concerning the life expectancy for individuals born with myelomeningocele (MM), with and without hydrocephalus. To ascertain such data was our first purpose. We have selected all patients with MM in our computer database, The Patient Data Management System (PDMS/fx). Data were transferred to Excel for primary and SPSS/PC for final analysis by Kaplan-Meier life survival curves. Of the 1,054 patients with MM in the Birth Defects Clinic and the University of Washington Medical Center (UWMC) of Seattle, 505 are now over the age of 21 (391) or have died (114). Follow-up information was available since 1994 for 132, 62% of whom we have had contact within the past 2 years. The second purpose was to identify potential health factors associated with long-term outcome of patients with MM. Patient variables chosen as relevant to survival included hydrocephalus, treatment before or after 1975, and health maintenance determined by outcome for those receiving care within the last 5 years or those last seen before. Age at last appointment and reason for visit were determined in order to identify age-specific health care needs of the adult population. Survival and medical needs were obtained from the UWMC's computer database, Mindscape, and by telephone survey for adult patients not seen in the last 2 years. Death is more frequent earlier in life for those MM patients with hydrocephalus. Ordinary degenerative disorders affect MM patients earlier in life than normals. Our data extend life expectancy for patients with MM and hydrocephalus to age 40 years with some reliability for those treated from 1957 to 1974, but only 24 years for those treated with modern techniques after 1974. More data is needed to determine long-term survival.

Early adiposity rebound and the risk of adult obesity.

OBJECTIVE: At 5 to 6 years of age, body fatness normally declines to a minimum, a point called adiposity rebound (AR), before increasing again into adulthood. We determined whether a younger age at AR was associated with an increased risk of adult obesity and whether this risk was independent of fatness at AR and parent obesity. DESIGN: A retrospective cohort study using lifelong height and weight measurements recorded in outpatient medical records. SETTING: Group Health Cooperative of Puget Sound (GHC), a health maintenance organization based in Seattle, Washington. PARTICIPANTS: All 390 GHC members (and their parents) born at GHC between January 1, 1965, and January 1, 1971, who had at least one recorded adult height and weight measurement plus two visits with recorded height and weight measurements in each of three age intervals: 1.5 to 4, 4 to 8, and 8 to 16 years. MAIN OUTCOME MEASURES: We calculated the mean body mass index (BMI) of each subject during young adulthood (age 21 to 29 years) and the BMI of the parents when each subject was 1.5 years of age. Adult obesity was defined as a BMI >/=27.8 for males and >/=27. 3 for females. Curves were fit to each subject's BMI values between ages 1.5 and 16 years, and the age and BMI at AR were calculated from these curves. Subjects were divided into tertiles of age at AR (early, middle, and late), BMI at AR, and parent BMI (heavy, medium, and lean). RESULTS: The mean age at AR was 5.5 years, and 15% of the cohort was obese in young adulthood. Adult obesity rates were higher in those with early versus late AR (25% vs 5%), those who were heavy versus lean at AR (24% vs 4%), those with heavy versus lean mothers (25% vs 5%), and those with heavy versus lean fathers (21% vs 5%). After adjusting for parent BMI and BMI at AR, the odds ratio for adult obesity associated with early versus late AR was 6.0 (95% CI, 1.3-26.6). CONCLUSION: An early AR is associated with an increased risk of adult obesity independent of parent obesity and the BMI at AR. Future research should examine the biological and behavioral determinants of AR.

Gestational diabetes and the risk of offspring obesity.

BACKGROUND: Intrauterine exposure to the metabolic alterations of maternal diabetes may increase the risk of later obesity. We determined whether offspring of mothers with diet-treated, gestational diabetes mellitus (GDM) have an increased risk of childhood obesity and examined the relationship between childhood obesity and metabolic markers of GDM. METHODS: At a health maintenance organization in Seattle, WA, we reviewed medical records to obtain the life-time height and weight measurements of 524, 8- to 10-year-old children whose mothers had been screened for GDM. Maternal plasma glucose and triglyceride levels were obtained in midgestation 1 hour after ingestion of 50 g of glucose. Those with glucose screening levels >/=7.77 mmol/L (140 mg/dL) underwent a 3-hour, 100-g, oral glucose tolerance test to determine GDM status. Cord serum insulin levels also were obtained at birth. Obesity was defined as an average body mass index between 5 and 10 years of age at or above the 85th percentile for age and sex. RESULTS: The prevalence of obesity was 19% in the 58 offspring of mothers with diet-treated GDM and 24% in the 257 offspring of mothers with negative glucose screen values. There also was no difference in mean body mass index (adjusted for age and sex) between these two groups of offspring. Among all 524 offspring, there was no significant increase in the rate of offspring obesity according to the quartile of maternal screening glucose, triglyceride, oral glucose tolerance test, or cord serum insulin level. CONCLUSION: Prenatal exposure to the metabolic effects of mild, diet-treated GDM does not increase the risk of childhood obesity.

Predicting obesity in young adulthood from childhood and parental obesity.

BACKGROUND: Childhood obesity increases the risk of obesity in adulthood, but how parental obesity affects the chances of a child's becoming an obese adult is unknown. We investigated the risk of obesity in young adulthood associated with both obesity in childhood and obesity in one or both parents. METHODS: Height and weight measurements were abstracted from the records of 854 subjects born at a health maintenance organization in Washington State between 1965 and 1971. Their parents' medical records were also reviewed. Childhood obesity was defined as a body-mass index at or above the 85th percentile for age and sex, and obesity in adulthood as a mean body-mass index at or above 27.8 for men and 27.3 for women. RESULTS: In young adulthood (defined as 21 to 29 years of age), 135 subjects (16 percent) were obese. Among those who were obese during childhood, the chance of obesity in adulthood ranged from 8 percent for 1- or 2-year-olds without obese parents to 79 percent for 10-to-14-year-olds with at least one obese parent. After adjustment for parental obesity, the odds ratios for obesity in adulthood associated with childhood obesity ranged from 1.3 (95 percent confidence interval, 0.6 to 3.0) for obesity at 1 or 2 years of age to 17.5 (7.7 to 39.5) for obesity at 15 to 17 years of age. After adjustment for the child's obesity status, the odds ratios for obesity in adulthood associated with having one obese parent ranged from 2.2 (95 percent confidence interval, 1.1 to 4.3) at 15 to 17 years of age to 3.2 (1.8 to 5.7) at 1 or 2 years of age. CONCLUSIONS: Obese children under three years of age without obese parents are at low risk for obesity in adulthood, but among older children, obesity is an increasingly important predictor of adult obesity, regardless of whether the parents are obese. Parental obesity more than doubles the risk of adult obesity among both obese and nonobese children under 10 years of age.