Short duration of marriage at conception as an independent risk factor for schizophrenia.

Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage. METHOD: Relative Risks (RR) for schizophrenia were estimated using continuous and stratified Cox proportional hazards models in the 90,079 offspring from the prospective population-based Jerusalem birth cohort study (1964-1976). Schizophrenia diagnos in offspring and parental diagnoses of schizophrenia or other psychiatric conditions were identified by cross-linkage to Israel's psychiatric case registry. DoM and paternal age at marriage were abstracted from birth certificates. RESULTS: In the full model, RR for schizophrenia decreased for each 5 years DoM: 0.83 (0.75-0.95), ptrend = 0.0015. Stratified analyses showed the greatest RR risk for DoM <2 years: 1.53 (1.11-1.66) with lesser risk for 2-4 years DoM: 1.38 (1.05-1.81) compared to more DOM of 10+ years. DoM effects were independent from parental psychiatric diagnoses (RRs = 2-6, p~0.00001), paternal age (1.34: p = 0.0001 /5 years- including fathers of 25-34 years). The apparent risk related to later fathers' age at marriage (1.27: p < 0.0001) was eliminated in after accounting for DoM and later paternal age. CONCLUSIONS: Offspring born to couples married for less than 3 years, across all paternal ages, harbored a small increased risk for schizophrenia, which was independent of parental psychiatric disorders and paternal age. Fathers who married late had particularly short DoM, which, along with paternal age, completely explained the risks related to later paternal age at marriage. Further studies are needed to replicate these results and examine if pathogenic pathways include prenatal immune activation.

Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort.

OBJECTIVES: Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women. STUDY DESIGN: We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13-55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables. RESULTS: Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54-0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03). CONCLUSION: Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.

Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964-2008.

BACKGROUND: Socioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women. METHODS: Residents of Jerusalem who gave birth between 1964-1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband's occupation and the woman's education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin. RESULTS: In multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend. CONCLUSIONS: SEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities.

Telomere length, family history, and paternal age in schizophrenia.

Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.

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.

Olfaction and cognition in schizophrenia: sex matters.

Cognitive and olfactory deficits occur in schizophrenia, but little is known whether sex modifies these deficits. We examined the relationship between olfaction and cognition in 55 schizophrenia patients and 32 healthy controls. Patients and controls demonstrated significant differences performing cognitive tasks. In patients, sex modified all relationships of odor identification to cognition. Female patients showed significantly stronger trends than male patients correlating better smell identification with higher scores on intelligence, memory, and attention, whereas their correlations of odor identification with executive functioning contradicted those of male patients. Odor acuity significantly correlated with several cognitive measures, especially in male patients, in whom better acuity was generally associated with better cognition. Female patients again differed significantly from males; odor acuity correlations with cognitive measures were weaker, or contradicted, those of male patients. These findings indicate significant sex differences in olfactory processing in schizophrenia. Combining the sexes in research analyses may obscure important differences.

Catatonic schizophrenia: a cohort prospective study.

BACKGROUND: In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia. METHODS: Data were analyzed in a cohort of 90,079 offspring followed from birth till ages 29-41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs "other schizophrenia." RESULTS: Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42-2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03-1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85-5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006). CONCLUSION: Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology.

Olfactory processing, sex effects and heterogeneity in schizophrenia.

INTRODUCTION: Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification. METHODS: Fifty-eight individuals with schizophrenia and 42 healthy comparison subjects were assessed on tests of odor sensitivity, smell identification and cognition. Negative symptoms were assessed with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome. RESULTS: In healthy males, increased odor detection sensitivity predicted better smell identification scores. In contrast, male schizophrenia patients showed a significant inverse relationship, in which increased odor sensitivity predicted lower smell identification scores. Odor sensitivity and smell identification were unrelated in both schizophrenia and healthy females. Olfactory processing was strongly linked to negative symptoms, but the relationships differed by sex. Emotional expression deficits were related to odor detection hypersensitivity in female patients, whereas smell identification deficits predicted these emotional deficits in male cases. CONCLUSION: Sex differences in olfactory functioning were identified in healthy subjects and in schizophrenia patients. Smell identification was related to negative symptoms in males with schizophrenia, whereas odor detection sensitivity predicted these features in females. Sex differences should be considered in future analyses that employ odor stimuli for neuropsychiatric research.

Paternal age related schizophrenia (PARS): Latent subgroups detected by k-means clustering analysis.

BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.

Older paternal age strongly increases the morbidity for schizophrenia in sisters of affected females.

The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers ≥35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations.

Time-to-pregnancy and risk of schizophrenia.

Schizophrenia has been linked to advanced paternal age, but the explanation is unknown. We questioned whether the incidence of schizophrenia would be related to male reproductive capacity, as reflected in the time taken to conceive. We measured the incidence of schizophrenia in relation to time to conception in a sub-group of 12,269 in the Jerusalem cohort whose mothers, interviewed post-partum, reported that the pregnancy had been intended. Compared with those conceived in less than 3 months, the unadjusted relative risks (RR) of schizophrenia associated with conception-waits of 3-5, 6-11 and 12+ months were 1.10 (95% confidence interval, 0.62-1.94), 1.41 (0.79-2.52) and 1.88 (1.05-3.37) with p for trend=0.035. This trend was attenuated somewhat by adjusting for paternal age, and was observed more strongly in offspring of fathers aged 30+ (p=.010). These findings suggest that factors associated with fecundability, either male or female, may contribute to the risk of schizophrenia.

Birth weight of offspring, maternal pre-pregnancy characteristics, and mortality of mothers: the Jerusalem perinatal study cohort.

PURPOSE: To explore the association between birth weight in offspring, a marker of the intrauterine environment, and mortality in their mothers, taking into account maternal pre-pregnancy characteristics, including maternal body mass index (BMI), smoking, and socioeconomic status. Distinguishing the effects of offspring's birth weight and pre-pregnancy characteristics on maternal outcome may provide clues regarding mechanisms underlying the association between birth weight and maternal mortality. METHODS: We studied long-term total mortality (average follow-up period, 29.1 years) in a population-based cohort of 13,185 mothers, aged 15 to 48 years at their offspring's birth, who delivered in West Jerusalem during 1974 through 1976. RESULTS: Univariate and multivariate Cox-proportional hazard models used to estimate the hazard of overall mortality among mothers indicated a nonlinear relationship with birth weight of offspring when introduced into the models as a continuous variable, and a linear positive association with maternal pre-pregnancy BMI. Inclusion of maternal BMI and other pre-pregnancy characteristics in the model did not alter the association between offspring's birth weight and mothers' all-cause mortality. When birth weight was introduced as a categorical variable, higher mortality was observed among mothers who gave birth to babies with birth weight less than 2500 g (hazard ratio [HR] = 1.90; 95% confidence interval [95%CI], 1.23-2.94) as compared to mothers whose offspring had birth weight between 3000 and 3499 g. The HR for mothers who gave birth to babies with birth weight 4000 g or more was 1.30 (95%CI, 0.88-1.91). CONCLUSIONS: Independent of pre-pregnancy maternal BMI and other characteristics, birth weight of offspring was associated with mortality in their mothers, suggesting that intrauterine metabolic events reflected by birth weight and not explained by maternal obesity, smoking, and socioeconomic status have remote consequences for maternal health. These findings underline the need to explore specific genetic and/or environmental mechanisms that account for these associations.

Effect of socioeconomic status and parents' education at birth on risk of schizophrenia in offspring.

Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder.

Incidence of schizophrenia among second-generation immigrants in the jerusalem perinatal cohort.

OBJECTIVE: Increased incidence of schizophrenia is observed among some immigrant groups in Europe, with the offspring of immigrants, ie "second-generation" immigrants particularly vulnerable. Few contemporary studies have evaluated the risk of schizophrenia among second-generation immigrants in other parts of the world. METHODS: We studied the incidence of schizophrenia in relation to parental immigrant status in a population-based cohort of 88 829 offspring born in Jerusalem in 1964-1976. Parental countries of birth were obtained from birth certificates and grouped together as (1) Israel, (2) Other West Asia, (3) North Africa, and (4) Europe and industrialized countries. Cox proportional hazards methods were used in adjusting for sex, parents' ages, maternal education, social class, and birth order. RESULTS: Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. Incidence of schizophrenia was not increased among second-generation immigrants in this birth cohort, neither overall nor by specific group. CONCLUSIONS: The difference in risk of schizophrenia among second-generation immigrants in Europe and in this Israeli birth cohort suggests that the nature of the immigration experience may be relevant to risk, including reasons for migration, the nature of entry, and subsequent position in the host country for immigrants and their offspring. Minority status may be of importance as, in later studies, immigrants to Israel from Ethiopia had increased risk of schizophrenia.

Preeclampsia and subsequent risk of cancer: update from the Jerusalem Perinatal Study.

OBJECTIVE: The purpose of this study was to examine the association between preeclampsia and cancer incidence. STUDY DESIGN: The Jerusalem Perinatal Study is a population-based cohort of all births to 41,206 residents of Western Jerusalem from 1964-76. Cancer incidence to 2004 was assessed by linkage of the cohort with the Israel Cancer Registry. Cox's proportional hazards models were constructed to estimate the hazard ratio for cancer among women who had had preeclampsia. RESULTS: Preeclampsia was associated with a 1.23-fold increased risk of cancer at all sites, a 37% increased risk of breast cancer, and more than a doubling of ovarian cancer risk. Analysis by morphologic condition yielded significantly increased risks for malignancies that were classed as cystic mucinous and serous (relative risk, 1.96; 95% CI, 1.00-3.83) and for ductal, lobular, and medullary carcinomas (relative risk, 1.40; 95% CI, 1.07-1.83). No differential association was observed by sex of offspring. CONCLUSION: Our study suggests that the previously described protective effect of preeclampsia on cancer is not universal.

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.

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.

Birthweight of offspring and mortality of parents: the Jerusalem perinatal study cohort.

PURPOSE: We sought to examine the association between birthweight in offspring and mortality in their parents. Distinguishing between risks of outcomes in mothers from fathers potentially provides clues as to the relative roles of genetic versus nongenetic mechanisms underlying these associations. METHODS: We studied total and cause-specific mortality in a population-based cohort of 37,718 mothers and 38,002 fathers whose offspring were delivered in West Jerusalem during 1964-1976, after an average follow-up of 34.12 years. RESULTS: Hazard models controlling for sociodemographic and lifestyle characteristics indicated a U-shaped relationship between offspring's birthweight and overall mortality, deaths from coronary heart disease, circulatory and other non-neoplastic causes in their mothers. Greater rates of mortality from coronary heart disease were observed among mothers who gave birth to babies with low (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.40-3.25) and high birthweight (HR, 1.98; 95% CI, 1.36-2.88), as compared with mothers whose offspring weighed 2500-3999 g at birth. Adjustment for maternal pre-eclampsia slightly attenuated these results. Multivariate models indicated a negative linear relationship (HR, 0.95; 95% CI, 0.91-0.99) between offspring's birthweight and overall mortality in their fathers. Unlike the association in mothers, the relation was noted primarily with deaths from "other causes." CONCLUSIONS: Birthweight of offspring is associated with parental mortality although the relation differs for fathers and mothers. These findings broaden previous observations that intra-uterine events have long-term consequences for adult health and support the need to explore genetic and/or environmental mechanisms underlying these associations.

Prepregnancy body mass index, hypertensive disorders of pregnancy, and long-term maternal mortality.

OBJECTIVE: Recent studies have shown increased maternal mortality rates after hypertensive disorders of pregnancy (HDP), but the reasons for this increase remain unclear. This study examines the relationship between elevated prepregnancy body mass index (BMI), HDP, and postpregnancy mortality. STUDY DESIGN: Data came from a 1975-1976 subset (n = 13,722 women) of a population-based cohort. Multiple logistic regression was used to examine the risk of HDP by BMI; age-adjusted Cox proportional hazards models were used to examine survival rates. RESULTS: Overweight (BMI, 25-29.9 kg/m2) and obesity (BMI, > or = 30 kg/m2) were associated with increased HDP (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.40-3.31 and OR, 5.51; 95% CI, 4.15-7.31]) and decreased survival (hazard ratio [HR], 1.42; 95% CI, 1.10-1.83 and HR, 2.43; 95% CI, 1.61-3.68), compared with normal weight (BMI, 18.5-24.9 kg/m2). HDP was significantly associated with increased mortality rates for women who survived > 15 years (HR, 1.94; 95% CI, 1.42-2.67]; HR adjusted for BMI, 1.65; 95% CI, 1.19-2.79]). A greater increase in risk of death after HDP was seen in the overweight women (HR, 1.86; 95% CI, 1.07-3.20) and obese women (HR, 2.90; 95% CI, 1.28-6.58), compared with normal weight women (HR, 1.26; 95% CI, 0.74-2.14). CONCLUSION: Elevated prepregnancy BMI is associated with increased risk of HDP, which are in turn is associated with increased long-term maternal mortality rates. This association between HDP and mortality rates increases with elevated prepregnancy BMI.