Survival after proton-beam irradiation of uveal melanomas.

PURPOSE: To evaluate the independent prognostic factors for survival, metastasis, local recurrence, and enucleation in patients who had undergone proton-beam therapy for posterior uveal melanomas. DESIGN: Interventional case series. METHODS: In this retrospective study, 224 consecutive incident cases were treated at the Biomedical Cyclotron Centre (Nice, France) from June 1991 to December 1997. Overall, metastasis-free, local recurrence-free, and enucleation-free survival rates were calculated according to the Kaplan-Meier method using the log-rank test. The multivariate prognostic analysis was performed using the Cox proportional hazards model. RESULTS: The 5-year overall survival rate was 78.1% (SE: 3.7%). A largest basal tumor diameter (LTD) below 10 mm and female sex were independently associated with a better prognosis. The 5-year metastasis-free survival rate was 75.6% (SE: 3.6%). Only an LTD above 10 mm and ciliary body involvement were independently associated with metastasis. Ten patients (4.5%) had a local recurrence, which was correlated with the risk of metastasis (P =.045). The 5-year enucleation-free survival rate was 69.6% (SE: 4.0%). Once again, an LTD below 10 mm and female sex were predictive of a better prognosis. CONCLUSION: Our results with proton-beam therapy correspond to those reported in the literature. This treatment strategy is safe and yields predictably good results. In addition to the two independent prognostic factors for survival and metastasis, namely LTD and ciliary body involvement, sex also had a significant impact in our case series, but the clinical relevance of this finding is unknown.

Preterm birth rates in Avon County, England, and urban Ukraine.

OBJECTIVE: We compared rates of total and spontaneous preterm birth in Avon County, England and urban Ukraine to explore whether adverse conditions in the former eastern bloc influenced the preterm rate. STUDY DESIGN: Women who had last menstrual period (LMP) in a specified time window were recruited from geographically defined areas. Data were gathered between 1992 and 1995, using maternal questionnaires and medical record abstraction, with comparable methods in both sites insofar as possible. There were 13731 births in Avon and 3087 in Ukraine. Rates of total and spontaneous preterm births were compared, taking account of maternal characteristics and other relevant variables. RESULTS: The total preterm birth rates were similar (5.9%, Ukraine; 5.5%, Avon) but the spontaneous preterm rate was about 60% higher in Ukraine (5.0% versus 3.1%). Maternal characteristics and measurement differences did not explain the discrepancy. CONCLUSION: The difference in the spontaneous preterm rates may reflect differences in obstetrical management resulting from shortages of medical supplies and equipment in Ukraine.

Hospital admissions during pregnancy in two urban areas of Ukraine.

Hospital admissions are generally regarded as a marker of severe pregnancy complications, and a low ratio of antenatal admissions to deliveries is considered an indicator of maternal-fetal well-being. We investigated the reasons for hospital admissions in a sample of deliveries from Ukraine, a country of the former eastern bloc. All hospitalisations were traced among 3099 women who delivered live singletons of at least 20 weeks gestation in two urban areas of Ukraine and data were abstracted from their medical records. More than a third of the women were admitted to hospital during their pregnancy, and 91% of the admissions were for a pregnancy complication, primarily threatened abortion or early labour. Median length of stay for all admissions was 12 days. The ratio of admissions to deliveries was 52 per 100. The Ukrainian ratio of hospitalisations to deliveries is notably higher than any that have been published in studies from the United States and Australia, reflecting patterns of care that stress hospital-based treatment. This high ratio does not necessarily mean that Ukrainian women are sicker, although that may be the case. The comparison of hospitalisation to delivery ratios is meaningful only when other factors, such as resources, patterns of care, costs and access, are taken into account.

Risk factors for spontaneous preterm birth in two urban areas of Ukraine.

The economic, social and health problems faced by former eastern bloc countries after the demise of the Soviet Union are unique in the recent history of Europe. We conducted a study in two urban areas of Ukraine, asking if the traditional predictors of preterm delivery continue to be associated with risk under these conditions. Subjects were pregnant women with last menstrual period (LMP) between 25 December 1992 and 23 July 1994. Self-completed questionnaires and the medical record provided data. We compared 137 spontaneous preterm deliveries with 2,886 full-term births, using all established risk factors for which we had data. Maternal age was the variable most strongly related to preterm birth. Being 18 or less had an odds ratio (OR) of 3.7; being 30+ had an OR of 2.5 relative to the reference group of age 25-29. Placental complications and pre-existing hypertension had ORs of 2.7 and 2.3, respectively, but the confidence interval included 1.0. Low net pregnancy weight gain (less than 10 kg) was significantly associated with preterm birth, but the rate of net weight gain was not. Marital status and educational category were only weakly related. We conclude that although Ukraine faced serious difficulties during its transition to a market economy, these problems did not generally alter the outcome of pregnancy in our sample when the classic risk factors for preterm delivery were present.

Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine.

Ukraine is a highly industrialized country with major environmental problems and deteriorating reproductive health. Heavy metals are known reproductive toxins; a study was undertaken to determine whether they were present at sufficient concentrations to be playing a major role in these health problems. Placental concentrations of arsenic, cadmium, copper, lead, mercury, and zinc were determined in 200 women from the general population of two urban areas of Ukraine, Kyiv and Dniprodzerzhinsk. Arsenic was detected in only 5% of the samples, lead in 22%, and mercury in 28%. Cadmium was detected in almost all samples, with a median of 5.2 ng/g. Concentrations of lead, mercury, and cadmium were low compared to those reported elsewhere, while zinc and copper concentrations were comparable.

Preterm birth in two urban areas of Ukraine.

OBJECTIVE: To determine whether the preterm birth rate was elevated in two urban areas of Ukraine, a former eastern bloc country that experienced serious economic, social, and health problems during its transition from a socialist republic. METHODS: We identified every pregnancy in a defined period in two urban sites where a separate study of pregnancy and childhood was being conducted. We obtained gestational age and vital status at delivery for each. Information about onset of labor and conduct of delivery was available for the subgroup enrolled in the collaborating study. RESULTS: Among 17,137 pregnancies, all but 6774 were terminated voluntarily. Among the continuing pregnancies, the preterm birth rate was 6.6% for live-born singletons of 20 or more weeks' gestation. Only 12% of preterm births involved medical intervention, the rest were idiopathic. The preterm birth rate was higher than in Europe (4.0% to 5.4%) and Canada (5.9%) but lower than for whites in the United States (8.4%). CONCLUSION: Live-born preterm birth rates are influenced by whether infants survive to be included in calculations. The high fetal mortality rate in Ukraine causes many preterm births to be excluded, thus lowering the rate. Frequent pregnancy termination and lack of ultrasound dating in Ukraine also might cause the preterm birth rate to be lower. Preterm birth rates, especially among live-born infants, are difficult to interpret and treacherous to compare across nations. Survival of the fetus and its health and development at birth are better indicators of reproductive outcome.

Polycyclic aromatic hydrocarbons in placenta.

Concentrations of chrysene, benz [a] anthracene, benzo [a]-pyrene, benzo [b] fluoranthene, indeno [1,2,3-c,d] pyrene, dibenz [a,h] anthracene, and benzo [g,h,i] perylene were measured in placentas from 200 women from two cities in Ukraine, Kyiv and Dniprodzerzhinsk. The participants had no special exposures and were chosen from among subjects in an ongoing study of reproductive health. All seven of the polycyclic aromatic hydrocarbons (PAHs) were found in all placentas, with the sole exception of benzo [a] pyrene in one placenta. Chrysene was present at the highest concentrations, with median 1.38 ng/g dry weight. Dibenz [a,h] anthracene and benzo [g,h,i] perylene had the lowest concentrations; each had median 0.73 ng/g dry weight. Concentrations in Kyiv were slightly higher than those in Dniprodzerzhinsk, but the difference was significant only for dibenz [a,h] anthracene. Dibenz [a,h] anthracene and benzo [g,h,i] perylene increased significantly with maternal body mass index, but other PAHs showed no such pattern. Placentas from deliveries in autumn or winter had slightly but not significantly higher concentrations. Concentrations were not related to maternal age. There were too few smokers in the sample for meaningful evaluation. No associations were seen between any of the placental PAH concentrations and birth weight of the infant.

Outcomes of 17,137 pregnancies in 2 urban areas of Ukraine.

OBJECTIVES: Frequent terminations of pregnancy and high rates of fetal loss have been reported, but not confirmed, in the former eastern bloc. A census of pregnancies in Ukraine, a former eastern bloc country, was conducted to determine the rates of these events. METHODS: All pregnancies registered in 2 urban areas were enumerated. During a 19-month period between 1992 and 1994, 17,137 pregnancies and their outcomes were recorded. RESULTS: Sixty percent of the pregnancies were voluntarily terminated, generally before the 13th week. In pregnancies delivered at 20+ weeks, fetal mortality was 29 per 1000, nearly 5 times the rate among Whites in the United States. There was a greater proportion of very early deliveries (20-27 weeks) in Ukraine, as well as higher death rates at all gestational ages. Perinatal mortality was estimated to be 35 per 1000, about 3 times the US rate. CONCLUSIONS: This is believed to be the first study in the former eastern bloc to ascertain all of the clinically recognized pregnancies in a specified period and to determine their outcomes. The data document elevated reproductive risks in a former Soviet state.

Levels of lipid peroxides in uncomplicated pregnancy: a review of the literature.

The literature on lipid peroxide levels in uncomplicated pregnancy is limited, but some reasonable conclusions are possible. Despite the lack of precision in the predominant measure of lipid oxidation, there is agreement across a large number of studies that the level of lipid peroxides in blood is generally higher in pregnant women than in nonpregnant women. During gestation, elevations appear by the second trimester and may taper off later in gestation, decreasing further after delivery. Lipid peroxides also are produced in placenta, but their pattern of change over the course of pregnancy is unclear. Lipid peroxides are important because their uncontrolled production can result in oxidative stress, with significant damage to cell integrity. There is a growing literature that associates oxidative stress with preeclampsia, a major cause of maternal and fetal morbidity. The higher levels of lipid peroxides seen in blood and the production of lipid peroxides in the placenta, even in uncomplicated pregnancies, make new baseline studies a priority. These studies should include measurements of lipids and blood volume, because they can influence marker values, with sensitive and specific measures of lipid peroxidation made at various points of gestation. From our review of the existing literature we conclude that the importance of oxidative stress in reproduction is just beginning to be appreciated and studied.

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine.

Substantial environmental pollution has been alleged in Ukraine, but little information is available to allow an assessment of the possible impact on humans. To help remedy this lack of information, it was of interest to investigate whether certain polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), or coplanar polychlorinated biphenyls (PCBs) were elevated in people from Ukraine. Samples of breast milk were obtained from 200 women from the cities of Kyiv and Dniprodzerzhinsk; Kyiv is the capital and Dniprodzerzhinsk is a highly industrialized city. The samples were combined into four pools by city and age, and analyzed for 7 PCDDs, 10 PCDFs, and 2 coplanar PCBs (126 and 169). The total of the measured PCDDs, expressed as toxic equivalent, ranged from 5.1 to 7.6 pg/g lipid; for PCDFs from 3.6 to 5.2, and for PCBs from 11 to 18 pg/g lipid. Results from the two cities were similar; older women had slightly higher concentrations than did younger women. Levels of these compounds seen in Ukraine were similar to or lower than those seen in other recent studies from European and Asian countries.

Organochlorines in breast milk from two cities in Ukraine.

Reports of environmental problems in the former Soviet Union, including excess use of pesticides, have led to concerns about high levels of contamination in humans, but little information is available to assess whether these concerns are warranted. Samples of breast milk from 197 women from two cities in Ukraine were analyzed for p,p'-DDT, p,p'-DDE, endrin, dieldrin, heptachlor epoxide, trans-nonachlor, oxychlordane, hexachlorobenzene, ss-hexachlorocyclohexane (HCH), and 18 polychlorinated biphenyl congeners, and results were compared to previous reports from Europe. The median ss-HCH concentration was 731 ng/g milk fat, which is higher than other reports from Europe but lower than reports from other parts of the world. The median DDE concentration was 2,457 ng/g milk fat, which is higher than most but not all other reports from Europe. Concentrations of other chemicals were comparable to or lower than other reports from Europe. Concentrations from the city of Kyiv were generally lower than those from Dniprodzerzhinsk, but the magnitudes of these differences were modest.

Variability of lipid hydroperoxides in pregnant and nonpregnant women.

Lipid peroxidation is thought to be important in numerous disease states, including pregnancy complications. Study of its role requires markers, but the variability of available markers in non-diseased populations has not been well-characterized. We examined the variability over time of blood lipid hydroperoxides, as measured by iodometric analysis, in 49 healthy young women, 21 nonpregnant and 28 pregnant. Lipid hydroperoxides from the same woman were very similar from one day to the next but were less stable over periods of a month or more. The correlation between measurements on consecutive days was 0.98; the correlation between measurements a month or more apart was 0.11. Variability over time was not attributable to seasonal effects or, among the pregnant women, to differences over the course of pregnancy. Knowledge of the variability of this and other markers of oxidative damage enables the development of appropriate study designs.

Effect of paternal alcohol consumption before conception on infant birth weight. ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Previous studies of paternal drinking and fetal growth in both animals and human have produced conflicting results. We evaluated the association between paternal drinking before conception and infant birth weight in a cohort of 9,845 liveborn singleton infant born to couples who participated in the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC), ALSPAC is a population-based cohort study in which women and their partners completed several self-administered questionnaires over the course of pregnancy. Of participating male partners, 20% were reportedly daily drinkers before conception, and 8% were considered moderately heavy or very heavy drinkers. Because maternal drinking is highly correlated with paternal, the analyses were stratified by maternal drinking in early pregnancy. We also adjusted for confounders and known predictors of birth weight. For all three maternal drinking strata, all adjusted mean differences in birth weight across levels of paternal drinking were similar, and all had confidence intervals that included zero. These findings persisted even after adjustment for other covariates and after stratification by parental smoking, race, and education. The size of the ALSPAC cohort, the large number of heavy drinkers, and the availability of data from the fathers themselves support the conclusion that paternal drinking before conception is not an important predictor of infant birth weight in humans.

Public health in central and eastern Europe and the role of environmental pollution.

The central and eastern European countries that composed the former Eastern Bloc have experienced an alarming decline in public health since the dissolution of the Soviet Union. Death rates have increased in most age groups. Life expectancy, especially among males, has decreased in many countries; in Russia, male life expectancy dropped by six years between 1989 and 1994. By 2020, these countries are projected to have smaller increases in life expectancy than any other geographic region. The conditions responsible for the excess mortality are cardiovascular disease, cancer, and injuries among adults. The major factors in the sharp increase are poverty, social disintegration, and crime, overlaid on historically high rates of smoking, alcohol use, and psychosocial stress. Environmental pollution, although common and sometimes severe in the former Eastern Bloc, is another, albeit not the chief, cause of the sharp decline in public health since 1989.

Birthweight of term infants and maternal occupation in a prospective cohort of pregnant women. The ALSPAC Study Team.

OBJECTIVE: To study the relation between birthweight of term infants and maternal occupation. METHODS: Information on job titles since the age of 16, and sociodemographic and other lifestyle factors were obtained by means of questionnaires as part of the Avon longitudinal study of pregnancy and childhood (ALSPAC), from a cohort of 14,000 pregnant women. The British 1990 standard occupational classification was used to code jobs within nine major job groups. RESULTS: For 9282 women who delivered term infants and reported a job for the relevant period, there was a significant difference in mean birthweight among the nine major job groups. A 148 g difference was found between the mean birthweight of infants born to women with professional occupations and those with plant and machine operative jobs. Multiple regression analysis adjusted for sex of infant, parity, maternal height, smoking, caffeine consumption, and race. After adjustment the maternal job was no longer significantly associated with birthweight. CONCLUSION: Despite the absence of a significant association between birthweight and job after adjustment, there were several findings which agreed with publications on maternal occupation and pregnancy outcome. The major job groups with the lowest birthweights included the following jobs; metal forming or welding, electric or electronic work, jobs in the textile trade, and assembling and working with equipment (mobile and stationary). The lack of an association may indicate that the study was of insufficient power to detect a small difference; it may indicate the presence of confounding variables that were not adjusted for or it may indicate that no association exists.

Postterm delivery: a challenge for epidemiologic research.

About 5% of babies are born postterm (that is, delivered after 42 completed weeks of gestation). Postterm infants experience more morbidity and mortality than term infants, prompting routine (and expensive) antenatal testing and active management of postterm pregnancies. This article reviews the epidemiology of postterm delivery. A few congenital conditions associated with disruption of the fetal-pituitary-adrenal axis as well as a rare maternal enzyme deficiency have long been identified with postterm delivery. In recent literature, environmental pollution, diet, and pharmaceutical agents have been associated with postterm birth. Very little systematic research has focused on identifying risk factors for this poorly understood birth outcome.

Agreement between self and partner reports of paternal drinking and smoking. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

BACKGROUND: We examined agreement between self and proxy reports of paternal drinking and smoking behaviour using data collected as part of the prospective, population-based Avon (England) Longitudinal Study of Pregnancy and Childhood. METHODS: Information on the smoking and drinking habits of pregnant women's male partners was obtained through self-administered questionnaires completed by pregnant participants and by their partners. For dichotomous indicators (e.g. smoker versus non-smoker), we evaluated self/proxy agreement by calculating Kappa coefficients and per cent agreement. For ordinal measures of smoking and drinking amounts, we calculated per cent perfect agreement, per cent agreement within one category, and Spearman correlation coefficients. Data from 8414 respondent pairs were included in the analyses. RESULTS: Men's and women's reports of paternal smoking and drinking status were in nearly complete agreement (95% and 98%, respectively). For analyses of smoking and drinking amounts, agreement within one category remained high (90% and 98% for smoking and drinking, respectively), but perfect agreement on amount was somewhat lower (81% and 71%, respectively). Per cent perfect agreement on smoking amount was especially low (50%) when non-smokers were excluded. When couples' reports were not in perfect agreement, women tended to report lower amounts of smoking and drinking for their partners compared to the men's self reports. CONCLUSIONS: Our results suggest that women's proxy reports of their partners' drinking and smoking status can be used with considerable confidence in reproductive epidemiological studies when the enrollment of both women and men as participants is infeasible for financial or logistical reasons. Caution is warranted, however, when proxy reports are used for more detailed information on smoking and drinking amounts.

Is there an association between preconception paternal x-ray exposure and birth outcome? The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood.

Diagnostic x-rays are performed commonly on men of reproductive age, yet little is known about the potential effects of these x-rays on the future unborn children of such men. This study examines the possibility that preconception diagnostic x-ray studies of fathers may adversely effect their newborns. The authors used prospectively collected data from the Avon Longitudinal Study of Pregnancy and Childhood (ALSPAC) for 7,678 birth records for women who gave birth in the County of Avon, England, in 1991-1992. Birth weight, gestational age, and fetal growth of infants whose fathers received diagnostic x-ray examinations likely to deliver significant gonadal doses within one year prior to conception were compared with infants whose fathers did not receive such x-rays. The mean birth weight of babies of exposed fathers was 3,358 g compared with a mean of 3,437 g in the unexposed group (p = 0.055). A similar difference was noted for intrauterine growth, 3,374 g exposed versus 3,437 g unexposed (p = 0.078). The downward trend in birth weight and fetal growth (birth weight adjusted for gestational age) persisted despite control for infants' sex and important parental variables such as age, height, race, education, occupational exposure, parity, and maternal smoking. Because medical x-rays are the largest controllable source of man-made ionizing radiation, more detailed study of the potential effect of paternal x-irradiation on progeny seems justified.

Incidence of fetal alcohol syndrome and prevalence of alcohol-related neurodevelopmental disorder.

We critique published incidences for fetal alcohol syndrome (FAS) and present new estimates of the incidence of FAS and the prevalence of alcohol-related neurodevelopmental disorder (ARND). We first review criteria necessary for valid estimation of FAS incidence. Estimates for three population-based studies that best meet these criteria are reported with adjustment for underascertainment of highly exposed cases. As a result, in 1975 in Seattle, the incidence of FAS can be estimated as at least 2.8/1000 live births, and for 1979-81 in Cleveland, approximately 4.6/1,000. In Roubaix, France (for data covering periods from 1977-1990), the rate is between 1.3 and 4.8/1,000, depending on the severity of effects used as diagnostic criteria. Utilizing the longitudinal neurobehavioral database of the Seattle study, we propose an operationalization of the Institute of Medicine's recent definition of ARND and estimate its prevalence in Seattle for the period 1975-1981. The combined rate of FAS and ARND is thus estimated to be at least 9.1/1,000. This conservative rate--nearly one in every 100 live births--confirms the perception of many health professionals that fetal alcohol exposure is a serious problem.