Glutathione-S-transferase M1, T1 and P1 polymorphisms, and breast cancer risk, in BRCA1/2 mutation carriers.

Variation in penetrance estimates for BRCA1/2 carriers suggests that other environmental and genetic factors may modify cancer risk in carriers. The GSTM1, T1 and P1 isoenzymes are involved in metabolism of environmental carcinogens. The GSTM1 and GSTT1 gene is absent in a substantial proportion of the population. In GSTP1, a single-nucleotide polymorphism that translates to Ile112Val was associated with lower activity. We studied the effect of these polymorphisms on breast cancer (BC) risk in BRCA1/2 carriers. A population of 320 BRCA1/2 carriers were genotyped; of them 262 were carriers of one of the three Ashkenazi founder mutations. Two hundred and eleven were affected with BC (20 also with ovarian cancer (OC)) and 109 were unaffected with BC (39 of them had OC). Risk analyses were conducted using Cox proportional hazard models adjusted for origin (Ashkenazi vs non-Ashkenazi). We found an estimated BC HR of 0.89 (95% CI 0.65-1.12, P=0.25) and 1.11 (95% CI 0.81-1.52, P=0.53) for the null alleles of GSTM1 and GSTT1, respectively. For GSTP1, HR for BC was 1.36 (95% CI 1.02-1.81, P=0.04) for individuals with Ile/Val, and 2.00 (95% CI 1.18-3.38) for carriers of the Val/Val genotype (P=0.01). An HR of 3.20 (95% CI 1.26-8.09, P=0.01), and younger age at BC onset (P=0.2), were found among Val/Val, BRCA2 carriers, but not among BRCA1 carriers. In conclusion, our results indicate significantly elevated risk for BC in carriers of BRCA2 mutations with GSTP1-Val allele with dosage effect, as implicated by higher risk in homozygous Val carriers. The GSTM1- and GSTT1-null allele did not seem to have a major effect.

Monitoring the therapy of lung cancer with alpha-1-acid glycoprotein.

Alpha-1-Acid glycoprotein is an acute-phase serum protein which is found in increased amounts in patients with a variety of cancers. This paper describes the application of discriminant analysis to the comparison of plasma levels of alpha-1-acid glycoprotein in 95 patients with lung cancer and 84 patients without known cancer. Using this technique, alpha-1-acid glycoprotein measurement yielded a sensitivity of 89% and specificity of 84% in the detection of active lung cancer. In addition, a new method for analysis of serial tumor marker data is presented which demonstrates that normalization of alpha-1-acid glycoprotein levels during antineoplastic therapy correlates with a significantly prolonged relapse-free survival in lung cancer patients.

Early gestational bleeding and pregnancy outcome: a multivariable analysis.

The effect of early vaginal bleeding on pregnancy outcome was assessed for 16 305 singleton stillborn and liveborn deliveries at three obstetric units in Jerusalem, Israel during 1975-1976. A total of 2385 women (14.6%) reported gestational bleeding before the seventh month of pregnancy. Of these, 2166 reported light bleeding (spotting), 191 heavy bleeding, and 28 both light and heavy bleeding. Logistic regression models revealed an unexpected interaction among light bleeding, hormone usage, and pregnancy outcome in that the risks of a low birth weight, pre-term and small-for-dates term delivery were significantly increased only for those women who had light bleeding and who had not used therapeutic hormones. Heavy vaginal bleeding, in contrast, was associated with an excess risk of these perinatal complications regardless of hormone usage. There was also a suggestion that certain subgroups of women with vaginal bleeding might be at an increased risk of delivering an offspring with congenital malformations.

Hepatitis c virus infection in employees of a large university hospital in Israel.

OBJECTIVE: To assess whether hospital work constitutes a risk factor for hepatitis C virus (HCV) infection among employees of a large hospital in Israel. DESIGN: Seroprevalence survey. SETTING: A 1,006-bed, tertiary-care university hospital in Jerusalem. PARTICIPANTS: All 5,444 employees (18-65 years old) were eligible; 4,287 (79%) participated in the survey. METHODS: Sera were tested for antibodies to HCV (anti-HCV) using a third-generation enzyme immunoassay. A third-generation strip immunoblot assay was used for confirmation. Participants were interviewed regarding their occupational history, and they completed a self-administered questionnaire covering history of non-occupational exposure to blood and country of birth. Other demographic information was obtained from the personnel department. Rates and odds ratios (ORs) were calculated, and multivariate logistic-regression analyses were performed to adjust for potential confounding variables. RESULTS: Anti-HCV was found in 0.9% of employees (37/4,287; 95% confidence interval, 0.6-1.1), ranging from 0.1% among those born in Israel to 5.7% among those born in Central Asia. After age, gender, social status, country of birth, and history of blood transfusion were controlled for in a logistic regression, occupational exposure to blood > or = 10 years was significantly associated with the presence of antibodies (OR, 2.6; P=.01). Presence of anti-HCV also was associated with country of birth (range: Israel OR, 1; West OR, 3.8 [P=.1]; Central Asia OR, 48.6 [P<.0001]) and history of blood transfusion (OR, 2.7; P=.01). No significant associations were found between anti-HCV and age, gender, social status, history of tattoo, acupuncture, current occupation, department, exposure to blood in current occupation, adherence to safety precautions, or history of percutaneous injury. The association with length of exposure was stronger (OR, 3.6; P=.01) when the same logistic regression was run excluding the outlier ethnic group of Central Asia. CONCLUSIONS: Hospital work does not seem to constitute a major risk factor for HCV infection in Israel today. A higher prevalence of anti-HCV among employees with longer versus shorter lengths of occupational exposure may be due to a cumulative effect of exposure over the years. Infection control efforts in recent years may have contributed to this association.

Correlation of rates of coronary artery bypass surgery, angioplasty, and cardiac catheterization in 305 large communities for persons age 65 and older.

OBJECTIVE: The rate of coronary artery bypass surgery (CABG) has been shown to vary greatly across geographic regions. This study examined whether these rates were associated with the rate of coronary artery angioplasty (PTCA) and with other community characteristics. DATA SOURCES/STUDY SETTING: The health care financing administration provided the number of Medicare hospitalizations in 1988 for conditions and procedures related to coronary artery disease. Information on physicians and hospitals was obtained from the Area Resource File, and the number of persons in each age, sex, and race category was obtained from US. census data. STATISTICAL METHODS: Age-and sex-adjusted hospitalization rates based on the patient's zip code of residence were calculated at the level of the Metropolitan Statistical Area (MSA) for white patients age 65 or older. Rates were obtained for 305 MSAs for CABG, PTCA, cardiac catheterization, angina, and myocardial infarction. PRINCIPAL FINDINGS: The rate of cardiac catheterization had a correlation of .72 with the CABG rate and .64 with the PTCA rate. The correlation of the PTCA and CABG rates with each other was .49. This correlation was not charged by adjusting for the rates of hospitalization for angina or myocardial infection, but it was reduced to only .05 (ns) after adjusting for the rate of cardiac catheterization. The rates of all three procedures had rank correlations of about .15 with the density of thoracic surgeons and about .30 with the density of hospitals with cardiac catheterization and open heart surgery units. CONCLUSIONS: Community CABG and PTCA rates tend to move in the same direction due to community factors that also affect the rates of cardiac catheterization. These community factors do not appear to include the rate of coronary artery disease, but may include resources or attitudes toward aggressive treatment of coronary artery disease.

Exposure to missile attacks: the impact of the Persian Gulf War on physical health behaviours and psychological distress in high and low risk areas in Israel.

The purpose of this study was to compare residents of an area (Tel-Aviv), which was severely afflicted by SCUD missiles during the Persian Gulf War (high risk region), to residents of a low-risk region (Jerusalem) in terms of: (a) changes in physical health, in use of medical or psychological services, and in health behaviours during the period of the war compared to the preceding month; (b) levels of psychological distress (somatization and anxiety) during the war; (c) characteristics of persons at highest risk for psychological distress. Respondents were randomly chosen and interviewed by telephone (N = 545 in Tel-Aviv, N = 406 in Jerusalem). The respondents in both regions reported significant yet similar deterioration in physical health status, and an increase in detrimental health behaviours during the Gulf War. Tel-Aviv residents had significantly higher levels of psychological distress as compared to residents of Jerusalem: in somatization 18 vs 12% respectively (OR = 2.44, CI = 1.39-4.28), in anxiety 34 vs 26% respectively (OR = 1.62, CI = 1.1-2.42). In addition to place of residence, age, ethnicity, religiosity and self-assessed health were identified as characteristics of persons at greater risk for psychological distress.

Bacteriocin production and competitiveness of Lactobacillus plantarum LPCO10 in olive juice broth, a culture medium obtained from olives.

A culture medium, named olive juice broth, which resembles the natural environment of Lactobacillus plantarum in the traditional Spanish-style green olive fermentation was obtained from green olives. In this medium, the bacteriocin-producing L. plantarum LPCO10 strain was able to produce bacteriocin throughout the incubation time (15 days). Bacteriocin purification from olive juice broth was achieved by a protocol including ammonium sulphate precipitation of cell-free, L. plantarum LPCO10 culture supernatants, and cation-exchange, hydrophobic-interaction and reversed-phase chromatographies. In a series of mixed cultures in olive juice broth, L. plantarum LPCO10 was able to dominate the bacteriocin-sensitive L. plantarum 128/2 strain, whereas the non-bacteriocin-producing, LPCO10 strain derivative, L. plantarum 55-1 strain did not show such capability. These results indicated that olive juice broth may be a valuable experimental substitute for olive fermentation brine in gaining more knowledge about the role of the bacteriocin-producing L. plantarum strains in the control of the Spanish-style green olive fermentation.

Complications of pregnancy and labor in former oral contraceptive users.

Complications of pregnancy and delivery, and obstetric interventions, were studied in a sample of Israeli women questioned post-partum about contraceptive use. The 2,953 women who had used the pill were compared with 13,630 controls. There were no significant differences between users and controls in the frequencies of bleeding in pregnancy, premature rupture of membranes, placenta previa, placental abruption, fetal distress or asphyxia, ABO incompatibility, hydramnios, transverse lie, cephalopelvic disproportion, and persistent occipitoposterior or post-partum hemorrhage. New cases of hypertension, varicose veins, thrombophlebitis, urinary tract infection, and cervicitis were reported in primigravidae and multigravidae without past histories of these conditions; there were no differences between oral contraceptive users and controls other than an excess of cervicitis in primigravidae among former users. There was a slight decrease in normal deliveries in former oral contraceptive users due to an increase in inductions of labor. On the other hand, rates of forceps and vacuum deliveries, caesarian sections, and interventions in the third stage did not differ between former oral contraceptive users and controls. These results indicate that former oral contraceptive users can anticipate the same frequency of complications of pregnancy and labor as women who have used other, or no, methods of contraception.

Long-term follow-up of children whose mothers used oral contraceptives prior to conception.

Anthropometric, psychometric and hematologic measurements were made at intervals in the first 3 years of life in a cohort of 732 infants, including 177 (24.2%) whose mothers used oral contraceptives (OC) prior to conception. Analysis of the data focused on weight and height measurements at 3, 9, 12, 24 and 36 months of age; hemoglobin and hematocrit at 9 months; development quotient (DQ) at 2 years and its components, posture, coordination, language and social; and intelligence quotient (IQ) at 3 years and its verbal and nonverbal components. Analyses were made for both sexes combined and males and females separately, by examining crude means, and means adjusted through linear multiple regression for birthweight, age of child at the time of examination, height of mother, mother's weight-for-height centile, birth-order, maternal and paternal education, and maternal smoking. No significant differences were found between the children whose mothers did or did not use oral contraceptives.

PIP: Anthropometric, psychometric, and hematologic measurements were made at intervals in the 1st 3 years of life in a cohort of 732 infants, including 177 (24.2%) whose mothers used oral contraceptives (OCs) prior to conception. Analysis of the data focused on weight and height measurements at 3, 9, 12, 24, and 36 months of age; hemoglobin and hematocrit at 9 months; development quotient at 2 years and its components, posture, coordination, language, and social; and intelligence quotient at 3 years and its verbal and nonverbal components. Analyses were made for both sexes combined and males and females separately, by examining crude means, and means adjusted through linear multiple regression for birthweight, age of child at time of examination, height of mother, mother's weight-for-height centile, birth order, maternal and paternal education, and maternal smoking.

Aggression, physical activity levels and sex role identity in teenagers exposed in utero to MPA.

Sex-dimorphic traits and behavior were measured in a 17-year old prospective study of 74 teenager boys and 98 girls who had been exposed to medroxyprogesterone acetate in utero compared with 459 boys and 546 girls not exposed. Bem Sex Role Identity scores were identical in exposed and non-exposed teenagers of each sex. There were no significant differences between MPA-exposed and non-exposed males or females on the Buss-Durkee overall aggression scale and on its assaultiveness subscale. Mothers of exposed males more often reported that teachers had complained that their offspring were naughty in school. No such difference was reported for females, nor for other school behaviors of dominance/aggression, activity, shyness and quietness. Exposed and non-exposed children were similar in the number of accidents experienced in childhood, as reported by their mothers, and in participation in competitive sports. These findings fail to support hypotheses posed by earlier researchers that exposure in utero to medroxyprogesterone acetate might alter sex-dimorphic behavior or traits in later life.

Long-term effects of MPA on human progeny: intellectual development.

Tests of verbal and spatial ability were done on 450 boys and 537 girls in their late teens of whom 73 and 97, respectively, had been exposed in utero to MPA. Exposed boys achieved higher raw scores than controls on verbal and spatial tests but the differences were explained by their more favorable demographic and social characteristics. Exposed girls did not differ from controls. Although, mothers of exposed boys reported that their offspring talked and walked later than controls, our results support the hypothesis that intrauterine exposure to MPA at contraceptive doses has no long-term effect on intellectual development.

PIP: Tests of verbal and spatial ability in a sample of teenagers who were exposed in utero to medroxyprogesterone acetate (MPA) suggest that fetal exposure to this drug at contraceptive dosages has no longterm effect on intellectual development. This double-blind study included 450 males and 537 females in late adolescence (average age of 18.6 years at time of testing), out of which 73 males and 97 females had been exposed to MPA in utero. All participants were administered a word incongruity test, word completion test, block rotation test, and Raven matrices test. Teenagers exposed to MPA scored higher than controls on both tests of verbal ability. On the word incongruity test, exposed boys scored an average of 0.8 points higher than controls while exposed girls scored 0.2 points higher than their nonexposed counterparts. On the word completion test, exposed boys scored 1.5 points higher than nonexposed controls while exposed girls' scores were 0.7 points higher. In the tests of spatial ability, MPA-exposed boys scored higher than male controls, but this difference was largely a result of education and ethnic group. There was no difference in spatial ability between exposed and nonexposed girls. Mothers of males exposed in utero to MPA reported that their sons talked and walked later than the norm; however, the validity of this observation could not be assessed. Previous studies that have examined the association between fetal exposure to contraceptive steroids and intellectual development have had inconsistent findings. The present study has the advantage of large numbers and the ability to control for demographic and social characteristics. Its finding that fetal exposure to MPA has no longterm effects on intellectual development should be reassuring to family planning programs that want to offer MPA as a contraceptive alternative.

Alcohol drinking in Jerusalem.

Alcohol use was assessed in a random sample of middle aged Jewish parents (1043 men and 591 women) who were interviewed at Visit 2 of the Lipid Research Clinics Prevalence Study in Jerusalem in 1976-80. A standard questionnaire probed drinking frequency (times per week) and quantity (number of drinks per week). Only 15.7% of men and 3.8% of women drank more than twice weekly, the mean number of drinks being 3.5 and 1.3 for men and women respectively. Teetotalism was rare and most subjects (61.9% of men and 55.1% of women) drank once or twice weekly, reflecting the high proportion of the Jews who use wine for sacramental purposes. Immigrants from North Africa drank more than native born Israelis or immigrants from Asia or Europe. Drinking was most frequent among men in lower status occupations, though the opposite was true of their wives. Season had a marked impact on the quantity and type of drinking, the mean number of drinks per week reaching a maximum in late winter and a minimum in summer. More beer was consumed in summer and more spirits in winter.

Does parity affect the neonatal outcome of very-low-birth-weight infants ?

OBJECTIVE: To evaluate the impact of parity on the neonatal outcome (survival, bronchopulmonary dysplasia and severe intraventricular hemorrhage) of very-low-birth-weight infants, accounting for sociodemographic, obstetric and perinatal variables. STUDY DESIGN: One hundred and eleven singleton premature infants with birth weights of 750--1250 grams, delivered between 1990 and 1994 and treated in the Hadassah University Hospitals in Jerusalem, were evaluated. In the analyses, variables with statistically significant association with the outcome variables were identified and entered together with parity as explanatory variables in a logistic regression. The results were analyzed with and without the inclusion of respiratory distress syndrome, representing an index of initial illness severity, in the multivariate model. RESULTS: Neonatal mortality was higher in the 2--11 parity group when compared with first born infants. This association was of borderline statistical significance (OR=3.3; P=0.09), and was evident only upon exclusion of respiratory distress syndrome from the equation. There was no association between parity and the development of bronchopulmonary dysplasia. The risk for developing severe intraventricular hemorrhage was higher in offsprings of multiparous women (OR=4.6; P=0,08 for parity 2-4, and OR=7.6; P=0.03 for parity 5--11). Respiratory distress syndrome was significantly associated with all the outcome variables and, to some extent, masked the relevance of pregnancy duration. A short hospitalization period before delivery was associated with increased mortality and with higher incidence of severe intraventricular hemorrhage. High initial Apgar scores appeared protective against severe intraventricular hemorrhage and bronchopulmonary dysplasia. CONCLUSION: Our results demonstrate a trend for increased survival of first born premature infants when compared with offsprings of subsequent deliveries, and an association between advanced parity and the development of severe intraventricular hemorrhage. Confirmation of these data by other studies is required before resultant implications are considered.

Neonatal outcome of inborn and transported very-low-birth-weight infants: relevance of perinatal factors.

OBJECTIVE: To compare the neonatal outcome (survival, intraventricular hemorrhage and bronchopulmonary dysplasia) of inborn and outborn very-low-birth-weight infants accounting for sociodemographic, obstetric and perinatal variables. STUDY DESIGN: Ninety-one premature infants with birth weights of 750-1250 g delivered between 1990 and 1994 in a hospital providing neonatal intensive care were compared with 76 premature babies delivered in a referring hospital. In the statistical analysis, variables with a statistically significant association with the outcome variables and dissimilar distributions in the two hospitals were identified and entered together with the hospital of birth as explanatory variables in a logistic regression. RESULTS: No statistically significant differences between the outcome variables of the two populations examined were observed, whether before or after accounting for the covariates. The odds ratios (outborns relative to inborns) were 1.18 for mortality, 1.25 for bronchopulmonary dysplasia and 1.53 for severe intraventricular hemorrhage. In the multivariate analyses, respiratory distress syndrome was significantly associated with mortality; both low birth weight and the presence of respiratory distress syndrome were associated with the development of bronchopulmonary dysplasia; the evolvement of severe intraventricular hemorrhage was associated with respiratory distress syndrome, initial low Apgar score, advanced multiparity and delivery at the 28-29th week compared to the 23rd-27th week. Antenatal steroid administration had a protective effect. CONCLUSION: Our results concur with the notion that a tertiary center is the optimal location for delivery of the high risk neonate. Improvement in medical and nursing care prenatally and at delivery and transportation, including frequent administration of antenatal steroids and earlier administration of surfactant prior to transportation, may minimize the disadvantage of delivery in a referring hospital.

The prevalence of a history of child sexual abuse among adults visiting family practitioners in Israel.

OBJECTIVE: To determine the prevalence of a history of child sexual abuse (CSA) in a random sample of adult patients presenting for routine health care to family practice clinics in Israel. METHOD: One thousand and five randomly selected patients aged 18 to 55, attending 48 clinics, participated in this questionnaire study. RESULTS: Twenty-five percent indicated that they had been sexually abused as children. More women reported CSA (p < .0001 ) than men, as did women originating from Western countries (p = .02) and those with more than 12 years of education (p = .01). There were no significant associations between CSA and the other socio-demographic variables examined. Fondling was the most common and intercourse the least common activity experienced. Forty-five percent of the perpetrators were previously known. The mean age at which the child sexual abuse began varied between 10 and 14. Only 45% of the subjects had ever told anyone about the experience. CONCLUSIONS: Since no other prevalence study has been reported to date in Israel, these findings suggest that as in other Western countries CSA is a relatively common problem. Family physicians and other health professionals should be aware of this high prevalence and its known potential for initial and long-term deleterious outcomes.

Studies in psychoneuroimmunology: psychological, immunological, and neuroendocrinological parameters in Israeli civilians during and after a period of Scud missile attacks.

Twenty-two male volunteers in Jerusalem were subjected to a battery of psychological tests at the height of the Iraqi Scud missile attacks on Israeli cities during the 1991 Persian Gulf War and again after the cessation of hostilities. Venous blood samples were taken at each time point. The separated mononuclear cells and plasma were cryopreserved, and a spectrum of immunological and neuroendocrine assays were performed on the preserved samples. Psychological testing indicated levels of anxiety were higher during the war than they were after the war ended, and both anxiety and anger during the hostilities were significantly elevated in comparison with prewar data. During the war, specific war-related pressures were greater than everyday pressures, and problem-focused coping was more evident than emotion-focused coping. Natural-killer cell activity and cell-mediated lympholysis were significantly elevated during the war, as were plasma levels of adrenocorticotrophic hormone, neurotensin, and substance P. The only biological test parameter found to be reduced during the war period was mononuclear cell thymidine incorporated in nonstimulated cultures.

Concurrent sexual and substance-use risk behaviours among female sex workers in Kenya's Coast Province: findings from a behavioural monitoring survey.

While many studies confirm the association between HIV, alcohol and injecting drug use by female sex workers (FSWs), little is known about their use of marijuana, khat and other substances and the association of these substances with HIV, risky sexual behaviour, and sexual violence. To better understand this association, data were analysed from a cross-sectional, behavioural survey of 297 FSWs in Mombasa, a well-known tourist destination and the second largest port in Africa and capital city of the Coast Province in Kenya. Among the FSWs, lifetime use of different substances was reported by 91% for alcohol, 71% for khat, 34% for marijuana, and 6% for heroin, cocaine, glue or petrol. The majority (79%) used more than one substance, and multiple-substance use was reported by all respondents who ever used marijuana, heroin, cocaine, glue and petrol. The risk of HIV acquisition was perceived as medium to high by 41% of respondents, 75% of whom attributed this risk to multiple partners. Sexual violence was reported by 48% of respondents, and 30% indicated that this happened several times. Despite HIV prevention programmes targeting FSWs in Mombasa, most of them continue to engage in risky sexual behaviours. This suggests that harm reduction strategies for substance use should be coupled with efforts to promote consistent condom use and partner reduction.

Conception-waits in fertile women after stopping oral contraceptives.

Conception-waits were studied retrospectively in 1,403 fertile oral contraceptive users who had stopped medication in order to conceive, and in 4,477 controls who stopped using other contraceptives. The proportion of pill users who conceived in the first month was 30% less than the others, but by the third month this difference had disappeared. There was no excess of long conception-waits in the oral contraceptive group nor any evidence for a cyclic return of fertility in them. There was a highly significant interaction between pill use and age, older women having a greater degree of temporary reduction in conceptions shortly after stopping the pill. There was also an interaction involving age and duration of use. In women who had used the pill for a short time, there was little age-effect, and in younger women there was little effect of the duration of use. Older women who had used the pill for several years, however, had a marked temporary reduction in fertility on stopping it.

PIP: Conception waits were studied retrospectively in 1403 fertile oral contraceptive (OC) users who had stopped medication in order to conceive, and in 4477 controls who stopped using other contraceptives. The proportion of pill users who conceived in the 1st month was 30% less than the others, but by the 3rd month, this difference had disappeared. There was no excess of long conception waits in the OC group nor any evidence for a cyclic return of fertility in them. There was a highly significant interaction between pill use and age, older women having a greater degree of temporary reduction in conceptions shortly after stopping the pill. There was also an interaction involving age and duration of use. In women who had used the pill for a short time, there was little age effect, and in younger women, there was little effect of the duration of use. Older women who had used the pill for several years, however, had a marked temporary reduction in fertility on its cessation.

A new approach to assessing the effect of birth order on the outcome of pregnancy.

PIP: The relationship between birth order and the risk of perinatal mortality has been explored in some detail. Different populations show somewhat different relationships, but in Europe and North America the predominant pattern is one of perinatal mortality falling from the 1st to the 2nd or 3rd birth and rising in subsequent births. Several authors have cautioned against interpreting the J shaped curve as showing that a high order birth is inherently more risky than a low order birth. An alternative explanation may simply be that the group of women presenting for, e.g., a 5th birth, contains a relatively high proportion of high risk women, who were at higher than average risk even in their 1st pregnancy. It is possible that the more successful reproducers withdraw from childbearing earlier, leaving, at each successive birth order, a greater concentration of poor reproducers. Some researchers have defined cohorts of women and compared the mortality rate for each cohort at different birth orders. However, this method produces its own distortions as long as the propensity to continue to another pregnancy is related to the outcome of previous pregnancies. A new approach is suggested for assessing the relationship between birth order and pregnancy risk. The term "birth order" is replaced by the term "parity" where parity is defined as the number of previous live births, and stillbirths of 28 weeks or more. An experimental model measuring perinatal mortality rate (PMR) was set up for an animal population. By contrast with this experimental model, the separate PMRs relating to each human reproductive history have been averaged together using wrong weights. If it were possible to estimate the correct weights one might yet be able to achieve a true estimate of parity risk in a human population. It is necessary to observe a cohort of women from their 1st pregnancy through to the end of their reproductive life--a period of about 25 years. Measuring parity risk for a real life population will enable assessment of the risk of a further delivery for an individual woman of given parity. Data on the reproductive histories of 16,583 West Jerusalem women were made available. Analysis for multiparae confirms that reproductive history is the most important factor in predicting risk in the current pregnancy. Of the elements of reproductive history examined, the incidence of 1 or more previous poor pregnancy outcomes showed the strongest association with increased risk in the current pregnancy. The risk of a poor outcome at the 1st pregnancy appears to be twice that at subsequent pregnancies, but no change in risk is observed between the 2nd and 5th birth orders. If there has been a previous poor pregnancy outcome, the risk of another is increased 4 fold. The risk of a poor pregnancy outcome at the 1st birth is substantially higher than the risk of a 1st poor outcome at higher parities.^ieng