Association between prenatal exposure to a 1-month period of repeated rocket attacks and neuropsychiatric outcomes up through age 9: a retrospective cohort study.

Exposure to gestational stress is implicated in increased risk for neuropsychiatric disorders in offspring. We assessed association between prenatal exposure to a 1-month period of repeated rocket attacks during the 2006 Second Lebanon War in Northern Israel and emergence of childhood neuropsychiatric disorders from birth through 9 years of age. Children born to women who were pregnant during the war (N = 6999) were identified and compared to children in the same district born a year later (N = 7054), whose mothers were not exposed to rocket attacks during pregnancy. Multivariable regression models assessed risk for attention deficit hyperactivity disorder, autism, epilepsy, depression and/or anxiety, or any of these disorders (composite outcome) in offspring. Models controlled for multiple confounders including parents' demographics, parity, maternal use of psychotropic medications during pregnancy, post-partum depression and parental psychiatric history. Results show that exposed and comparison groups did not differ with respect to demographics, parity or psychiatric history. Exposed and comparison groups were similar with regard to gestational age and weight at birth. Multivariable models did not demonstrate an association between exposure to rocket attacks during pregnancy and neuropsychiatric outcomes by age 9. No interactions were found between exposure and gestational trimester at exposure or child's sex. Our findings suggest that in utero exposure to isolated, 1-month repeated rocket attacks on a civilian population was not associated with major neuropsychiatric outcomes in children by age 9. Future studies should evaluate whether this exposure is associated with psychiatric and/or other health-related outcomes later in life.

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.

Mortality, cancer incidence, and survival in parents after bereavement.

PURPOSE: The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents. METHODS: We used a population-based birth cohort (1964-1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05-1.32 in mothers; HR = 1.10, 95% CI: 1.01-1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23-2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22-2.34 in mothers and HR = 1.25; 95% CI: 1.02-1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9-10, 0-3 years; HRs = 0.9-1.0, 9+ years; P(heterogeneity) ≤ 3 × 10(-32)). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7-8.7, 0-3 years; HRs = 0.9-1.0, 9+ years). CONCLUSIONS: Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress.

Parental smoking during pregnancy and offspring cardio-metabolic risk factors at ages 17 and 32.

OBJECTIVE: To examine the association of maternal and/or paternal smoking during pregnancy with offspring cardio-metabolic risk (CMR) factors at adolescence and early adulthood, taking into account socio-demographic, medical and lifestyle characteristics of parents and offspring, as well as offspring common genetic variation. METHODS: We used a population-based cohort of all 17 003 births in Jerusalem during 1974-76, with available archival data on parental and birth characteristics. Measurements at age 17 were assessed at military induction examinations for 11 530 offspring. 1440 offspring from the original 1974-1976 birth cohort were sampled using a stratified sampling approach, and were interviewed and examined at age 32. Parental smoking during pregnancy (i.e. maternal, paternal and any parent) was primarily defined dichotomously (any number of cigarettes smoked daily by mother or father during pregnancy vs. non-smokers). Additionally, smoking was assessed by quantity of cigarettes smoked daily. Linear regression models were used to evaluate the associations of parental smoking during pregnancy with various offspring CMR factors, after controlling for potential confounders and for genetic variation in candidate genes. RESULTS: Prevalence of exposure to parental smoking in-utero (i.e. smoking of any parent) was 53.2% and 48.4% among the 17 years old and 32 years old samples, respectively. At age 17, smoking of at least one parent during pregnancy was significantly associated with weight (B = 1.39), height (B = 0.59), BMI (B = 0.32) and pulse rate (B = -0.78) (p-values < 0.001). At age 32, parental smoking, adjusted for covariates, was associated with 2.22 kg higher mean offspring weight, 0.95 cm higher mean offspring height, 0.57 kg/m(2) higher BMI, and 1.46 cm higher waist-circumference (p-values ≤ 0.02). Similar results, reflecting a dose response, were observed when maternal and paternal smokings were assessed by number of cigarettes smoked daily. CONCLUSIONS: This prospective study demonstrates a potential long-term adverse effect of parental smoking during pregnancy on offspring health and calls for increasing efforts to promote smoking cessation of both parents before pregnancy.

Associations of maternal pre-pregnancy and gestational body size with offspring longitudinal change in BMI.

OBJECTIVES: Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed. METHODS: A birth cohort of 1400 adults, with data at birth, age 17 and 32 years was used. After genotyping offspring, genetic scores, predictive of exposures and outcome were created, and linear regression models with and without scores were fit to examine the associations of mppBMI and GWG with ΔBMI. RESULTS: A one SD change in mppBMI and GWG was associated with a 0.83 and a 0.75 kg/m² increase in ΔBMI, respectively. The association between mppBMI and offspring ΔBMI was slightly attenuated (12%) with the addition of genetic scores. In the GWG model, a significant substantial 28.2% decrease in the coefficient was observed. CONCLUSIONS: This study points to an association between maternal excess weight in pregnancy and offspring BMI change from adolescence to adulthood. Genetic factors may account, in part, for GWG/ΔBMI association. These findings broaden observations that maternal obesity-related phenotypes have long-term consequences for offspring health.