Prenatal stress and affective disorders in a population birth cohort.

OBJECTIVES: Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort. METHODS: Using data on 90079 offspring born in Jerusalem in 1964-1976 and linked to Israel's psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab-Israeli war of June 1967 and incidence of mood disorders. RESULTS: Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68-5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996-5.99, p = 0.054) and for all 'other' mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68-7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73-11.24, p < 0.0001). CONCLUSIONS: A time-limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.

Very high birth weight of offspring is associated with an increased risk of leukemia in their mothers: results of a population-based cohort study.

Although the association between birth weight and childhood leukemia is well described, the relation between a child's birth weight and parental risk of leukemia is unknown. We linked data from the Jerusalem Perinatal Study to the Israel Cancer Registry to ascertain the incidence of leukemia in mothers and fathers in relation to their offspring's birth weight. Birth weight >or=4500 g in any of the offspring was associated with a >3-fold risk of leukemia in mothers, but not fathers. Potential mechanisms include shared exposures of high birth weight infants and their mothers, possibly to radiation or growth factors, or genetic pathways leading to both high birth weight and leukemia.

The interval between cancer diagnosis among mothers and offspring in a population-based cohort.

BACKGROUND: Familial cancers may be due to shared genes or environment, or chance aggregation. We explored the possibility that ascertainment bias influences cancer detection in families, bearing upon the time interval between diagnosis of affected mothers and offspring. METHODS: The Jerusalem Perinatal Study (JPS) comprises all mothers (n = 39,734) from Western Jerusalem who gave birth 1964 -1976 and their offspring (n = 88,829). After linking identification numbers with Israel's Cancer Registry we measured the absolute time interval between initial cancer diagnoses in affected mother-offspring pairs. We tested the probability of obtaining intervals as short as those observed by chance alone, using a permutation test on the median interval. RESULTS: By June 2003 cancer had developed in 105 mother-offspring pairs within the cohort. Common sites among mothers were breast (47%), colorectal (9%), non-Hodgkin lymphoma (NHL) (8%) and cervix (7%), while for offspring in affected pairs common cancers were leukemia (12.4%), thyroid (13.3%), NHL (10.5%), breast (10.5%) and melanoma (7.6%). The median interval between diagnoses was 5.9 years, but for 33% of affected pairs the interval was < or =3 years. The probability of this occurring by chance alone was 0.03. This held true whether the offspring's or mother's diagnosis was first (P < 0.01). CONCLUSIONS: In a population-based cohort followed for three decades, the absolute interval between the diagnosis of cancer in mothers and their offspring is shorter than expected by chance. Explanations include shared environmental exposures or the possibility that cancer ascertainment in one pair member affects health behaviors in the other resulting in early diagnosis. The latter may bias the estimation of anticipation and survival in familial cancers.

Ethnic ancestry and increased paternal age are risk factors for breast cancer before the age of 40 years.

To study the risk factors associated with breast cancer in women younger than 40 years, a cohort study (The Jerusalem Perinatal Study) of 42 822 female offspring born in hospitals in West Jerusalem during 1964-1976 was carried out. Hazard ratios of potential parental and perinatal risk factors for early breast cancer were measured. The overall incidence of breast cancer was 5.2/100 000 person-years. The highest incidence was found among Jewish women of West Asian ancestry (8.6/100 000 person-years), specifically those whose maternal grandfathers were born in Iraq, Iran or Afghanistan (9.5/100 000 person-years). Using Cox models we found independent risk factors for early breast cancer to be paternal age (relative risk/year=1.06, 95% confidence interval=1.02-1.10, P=0.005), and ancestry from Iraq/Iran/Afghanistan (relative risk=3.1, 95% confidence interval=1.50-6.52, P=0.002). The study confirms a previously observed effect of advanced paternal age on the occurrence of early breast cancer and identifies a novel population group at increased risk for the disease. The excess risk of early breast cancer associated with ancestry from Iraq, Iran and Afghanistan suggests involvement of genetic determinants, environmental exposures and/or lifestyle factors and mandates further investigation.

Associations of social environment, socioeconomic position and social mobility with immune response in young adults: the Jerusalem Perinatal Family Follow-Up Study.

OBJECTIVES: Immune response to cytomegalovirus (CMV) impacts adult chronic disease. This study investigates associations of childhood and adulthood social environment, socioeconomic position (SEP) and social mobility with CMV response in young adults. DESIGN: Historical prospective study design. SETTING: Subcohort of all 17 003 births to residents of Jerusalem between 1974 and 1976. PARTICIPANTS: Participants included 1319 young adults born in Jerusalem with extensive archival and follow-up data, including childhood and adulthood SEP-related factors and anti-CMV IgG titre levels and seroprevalence measured at age 32. MAIN EXPOSURE AND OUTCOME MEASURES: Principal component analysis was used to transform correlated social environment and SEP-related variables at two time points (childhood and adulthood) into two major scores reflecting household (eg, number of siblings/children, religiosity) and socioeconomic (eg, occupation, education) components. Based on these components, social mobility variables were created. Linear and Poisson regression models were used to investigate associations of components and mobility with anti-CMV IgG titre level and seroprevalence, adjusted for confounders. RESULTS: Lower levels of household and socioeconomic components in either childhood or adulthood were associated with higher anti-CMV IgG titre level and seropositivity at age 32. Compared with individuals with stable favourable components, anti-CMV IgG titre level and risk for seropositivity were higher in stable unfavourable household and socioeconomic components (household: ß=3.23, P<0.001; relative risk (RR)=1.21, P<0.001; socioeconomic: ß=2.20, P=0.001; RR=1.14, P=0.01), downward household mobility (ß=4.32, P<0.001; RR=1.26, P<0.001) and upward socioeconomic mobility (ß=1.37, P=0.04; RR=1.19, P<0.001). Among seropositive individuals, associations between household components and mobility with anti-CMV IgG titre level were maintained and associations between socioeconomic components and mobility with anti-CMV IgG titre level were attenuated. CONCLUSIONS: Our study provides evidence that accumulating low SEP from childhood through adulthood and social mobility may compromise immune response in young adulthood.

The risk of cancer following hospitalization for infection in infancy: a population-based cohort study.

BACKGROUND: The relation between infections in infancy and subsequent cancer risk in children and young adults is controversial. Our aim was to examine this association in the Jerusalem Perinatal Study, a population-based cohort comprising all offspring from western Jerusalem and surroundings born from 1964 to 1976. METHODS: Identity numbers of non-malformed singletons with recorded data about hospital admission in the 1st year of life (n = 24,554) were linked to the Population and Cancer Registries. Person-year incidence rates were calculated for the exposed (admitted for infection) and nonexposed (not admitted for infection) groups from birth to date of cancer diagnosis, death, or December 31, 2004. We used Cox proportional hazards models to adjust for covariates associated with hospitalization. RESULTS: The median follow-up was 36 years. Cancer developed in 283 individuals. Hospitalization for infection was not associated with overall cancer risk [risk ratio (RR), 0.88; 95% confidence interval (95% CI), 0.56-1.37]. The incidence rate for non-Hodgkin's lymphoma was higher in the exposed compared with the nonexposed group (RR, 3.46; 95% CI, 1.38-8.68), remaining unchanged after controlling for birth weight, gender, and maternal education. Leukemia risk was not significantly associated (RR, 0.44; 95% CI, 0.06-3.24) with hospitalization for infection. CONCLUSIONS: Hospital admission in the 1st year of life due to infection is associated with an increased risk of non-Hodgkin's lymphoma. This is consistent with observations that mild immunodeficiencies predispose to lymphoma. Survival of infants with subtle immune defects, who may have previously succumbed to their infection, may contribute to the increased incidence of non-Hodgkin's lymphoma observed over the last 50 years.

Birth weight and other risk factors for acute leukemia in the Jerusalem Perinatal Study cohort.

OBJECTIVES: To assess the effect of birth weight of children and their siblings and other perinatal/parental factors on the risk of acute leukemia. METHODS: We linked data from the Jerusalem Perinatal Study, a population-based research cohort (n = 88,829) of offspring born 1964 to 1976, with Israel's Cancer Registry. Risk factors for acute leukemia were assessed using univariate and multivariate proportional hazards models. RESULTS: Leukemias developed in 65 individuals [24 acute myeloid leukemias (AML) and 41 acute lymphoblastic leukemias (ALL)]. A positive linear relation was found between gender-adjusted birth weight and all leukemias [hazard ratio (HR) 1.85, 95% confidence interval (95% CI) 1.1-3.0] and AML (HR 2.9, 95% CI 1.3-6.4). The association between birth weight and AML was especially notable among infants (HR 8.14, 95% CI 1.8-38.9 for age 0 to 1 year) but was also observed among subjects ages >14 years at diagnosis. The relation was particularly strong among females (P = 0.001). Other risk factors for AML risk on univariate analysis were maternal origin, socioeconomic status, birth weight of sibling > 3,500 g, and family size. On multivariate analysis, only birth weight retained borderline significance (adjusted HR 2.38 per kg, 95% CI 1.0-5.7). Significant predictors for ALL in both univariate and multivariate analyses were male sex (adjusted HR 1.92, 95% CI 1.0-3.7) and birth weight categories > or = 3,000 g introduced into the model as nonlinear terms. CONCLUSION: Birth weight is associated with an increased risk of acute leukemia in infants, children, and young adults. Perinatal factors play a role in the development of childhood leukemias, but the patterns of association vary by leukemia type.

Prostate cancer in fathers with fewer male offspring: the Jerusalem Perinatal Study cohort.

Recent studies have suggested the involvement of loci on the Y chromosome in prostate cancer. We studied the relative risk (RR) of prostate cancer in relation to sex ratio of offspring in a cohort of 38,934 Israeli men who were followed from the birth of their offspring (in 1964 through 1976) until 2005. Cox models were used to adjust for changes in incidence over time, age, the man's year of birth, and social and ethnic variables. A total of 712 men were diagnosed with prostate cancer. Compared with men who had at least one son, men with only daughters had an increased risk of prostate cancer (adjusted RR = 1.40, 95% confidence interval [CI] = 1.20 to 1.64, P<.0001). In men with one, two, or three or more offspring, the relative risks associated with absence of sons were 1.25 (95% CI = 1.00 to 1.56), 1.41 (95% CI = 1.04 to 1.91), and 1.60 (95% CI = 1.05 to 2.43), respectively. Men with no daughters showed no statistically significantly altered risk, compared with men who had offspring of both sexes. The relative risk of prostate cancer decreased as the number of sons increased (P(trend)<.0001) but did not change with the number of daughters. These findings suggest that a Y chromosome locus may be involved in prostate cancer risk in this population.

Cancer after pre-eclampsia: follow up of the Jerusalem perinatal study cohort.

OBJECTIVE: To compare the incidence of cancer among women with and without a history of pre-eclampsia. DESIGN: Cohort study. SETTING: Jerusalem perinatal study of women who delivered in three large hospitals in West Jerusalem during 1964-76. PARTICIPANTS: 37 033 women. MAIN OUTCOME MEASURES: Age adjusted and multivariable adjusted hazard ratios for cancer incidence for the entire cohort and for women who were primiparous at study entry. RESULTS: Cancer developed in 91 women who had pre-eclampsia and 2204 who did not (hazard ratio 1.27, 95% confidence interval 1.03 to 1.57). The risk of site specific cancers was increased, particularly of the stomach, ovary epithelium, breast, and lung or larynx. The incidence of cancer of the stomach, breast, ovary, kidney, and lung or larynx was increased in primiparous women at study entry who had a history pre-eclampsia. CONCLUSIONS: A history of pre-eclampsia is associated with increases in overall risk of cancer and incidence at several sites. This may be explained by environmental and genetic factors common to the development of pre-eclampsia and cancer in this population.