We aimed to identify the reproductive targets of pollutants by studying high exposures. We entered into a collaborative agreement with the Ukrainian Institute of Pediatrics, Obstetrics and Gynecology and the University of Bristol in 1993 to conduct the research described here. The Ukraine Placental Study had the following goals: 1. To document the levels of common pollutants experienced by pregnant women in two urban areas, using environmental measurements and biological markers 2. To describe the reproductive outcomes of these women 3. To determine what relationship, if any, exists between the estimates of exposure and the outcome of the pregnancies. PAHs. Concentrations of PAHs 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 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. Hospital admissions. We investigated the reasons for hospital admissions in a sample of deliveries from Ukraine, a country of the former eastern bloc. We enumerated all hospitalizations among 3,099 women who delivered live singletons of at least 20 weeks gestation in two urban areas of Ukraine and abstracted data 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 labor. Median length of stay for all admissions was 12 days. The ratio of admissions to deliveries was 52 per 100.The Ukrainian ratio of hospitalizations 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. Preterm birth. 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 LMP between 12/25/92 and 7/23/94. Self-completed questionnaires and the medical record provided data. We compared 137 spontaneous preterin deliveries with 2886 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 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. Comparison with England. We compared the rates of spontaneous preterm birth in Avon County, England and in two urban areas of Ukraine, using the same study methodology in both sites and accounting for differing in maternal risk factors. We used data from the European Longitudinal Study of Pregnancy and Childhood; eligibility required residence in geographically defined areas and last menstrual period in a specific time window. Data were collected by questionnaire and medical record abstraction between 1992 and 1995, using comparable instruments and methods in both countries. Preterm births were classified into those that were spontaneous, and those that involved medical intervention. Rates of spontaneous preterm birth were compared in the two sites, taking account of maternal characteristics. Placenta and birth weight. We investigated whether the difficult conditions in the former eastern bloc in the last decade might have altered the weight of the placenta or its relationship to other measures of fetal size from what has historically been reported. Placentas were obtained from 1621 singleton births of at least 28 weeks gestation in a Ukrainian city during 1993-94, using a systematic protocol. Information on maternal characteristics was obtained from two questionnaires completed by the mothers. Data on pregnancy complications were abstracted from the medical record, as were absolute measures of birth size (infant weight, infant length, crown-rump length, and head circumference). We examined the relationship of placental weight and ratio to these variables. The range of placental weight was 100 to 1000 grams, with a mean of 470 g. Mean placental ratio was 13.9%. Placental weights increased and placental ratios decreased with gestational age. Larger ratios were related to larger maternal BMI. Absolute measures of infant size and placental weight were mutually positively correlated. Placental ratio, infant length, and ponderal index were nearly uncorrelated. Ukrainian placentas were of similar absolute and relative weight as those historically reported, as was their relationship to other indicators of infant size. Alcohol and breastfeeding.
We aim ed to replicate a previous study of one-year olds that reported deficit in motor development associated with moderate alcohol use during lactation, using different but comparable population. The mental development of 915 18-month-old toddlers from a random sample of a longitudinal population-based study in England was measured using the Griffiths Developmental Scales. Frequent self-administered questionnaires during and after pregnancy provided maternal data. The dose of alcohol available to the lactating infant was obtained by multiplying the alcohol intake of the mother by the proportion of breast milk in the infant's diet. We compared this dose with the Griffiths scales, taking into account potential confounding variables in the sample. ACE inhibitors. We explored the association between enalapril exposure and adverse outcomes in pregnancy, taking into account other possible risk factors. We analyzed a series of all usable cases reported to the FDA between 1986 and 2000 in which enalapril was a suspect drug for the observed adverse outcomes (N=110). Parameters of exposure and reported outcomes as well as information on potentially confounding variables were systematically abstracted from this series by a single physician. Because exposure to ACE inhibitors after the first trimester of pregnancy had been associated with adverse outcomes in the existing literature, we divided the cases into those exposed in the first trimester only (considered as the baseline group) and cases exposed beyond or after this time. Frequency of reported adverse outcomes in the second group was compared with those in the baseline group; odds ratios were computed, taking account of potentially confounding variables by logistic regression where appropriate. Dr. Little has retired; Beth Gladen (DIR/BB) will assume role of PI on this Project.
| Little, R E; Gladen, Beth C; Birmingham, Karen et al. (2004) Preterm birth rates in Avon County, England, and urban Ukraine. Eur J Obstet Gynecol Reprod Biol 113:154-9 |
| Gladen, Beth C; Shkiryak-Nyzhnyk, Zoreslava A; Chyslovska, Nataliya et al. (2003) Persistent organochlorine compounds and birth weight. Ann Epidemiol 13:151-7 |
| Little, Ruth E; Zadorozhnaja, Tamara D; Hulchiy, Olesya P et al. (2003) Placental weight and its ratio to birthweight in a Ukrainian city. Early Hum Dev 71:117-27 |
| Little, Ruth E; Northstone, Kate; Golding, Jean et al. (2002) Alcohol, breastfeeding, and development at 18 months. Pediatrics 109:E72-2 |
| Sasco, Annie J; Laforest, Laurent; Benhaim-Luzon, Veronique et al. (2002) Smoking and its correlates among preadolescent children in France. Prev Med 34:226-34 |
| Monaghan, S C; Little, R E; Hulchiy, O et al. (2001) Risk factors for spontaneous preterm birth in two urban areas of Ukraine. Paediatr Perinat Epidemiol 15:123-30 |
| Little, R E; Little, A S; Chislovska, N et al. (2001) Hospital admissions during pregnancy in two urban areas of Ukraine. Paediatr Perinat Epidemiol 15:323-7 |
| Gladen, B C; Zadorozhnaja, T D; Chislovska, N et al. (2000) Polycyclic aromatic hydrocarbons in placenta. Hum Exp Toxicol 19:597-603 |
| Zadorozhnaja, T D; Little, R E; Miller, R K et al. (2000) Concentrations of arsenic, cadmium, copper, lead, mercury, and zinc in human placentas from two cities in Ukraine. J Toxicol Environ Health A 61:255-63 |
| Monaghan, S C; Little, R E; Hulchiy, O et al. (2000) Preterm birth in two urban areas of Ukraine. Obstet Gynecol 95:752-5 |
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