Significant interactions between maternal PAH exposure and single nucleotide polymorphisms in candidate genes on B[ a ]P-DNA adducts in a cohort of non-smoking Polish mothers and newborns.

Polycyclic aromatic hydrocarbons (PAH) are a class of chemicals common in the environment. Certain PAH are carcinogenic, although the degree to which genetic variation influences susceptibility to carcinogenic PAH remains unclear. Also unknown is the influence of genetic variation on the procarcinogenic effect of in utero exposures to PAH. Benzo[ a ]pyrene (B[ a ]P) is a well-studied PAH that is classified as a known human carcinogen. Within our Polish cohort, we explored interactions between maternal exposure to airborne PAH during pregnancy and maternal and newborn single nucleotide polymorphisms (SNPs) in plausible B[ a ]P metabolism genes on B[ a ]P-DNA adducts in paired cord blood samples. The study subjects included non-smoking women ( n = 368) with available data on maternal PAH exposure, paired cord adducts, and genetic data who resided in Krakow, Poland. We selected eight common variants in maternal and newborn candidate genes related to B[ a ]P metabolism, detoxification, and repair for our analyses: CYP1A1 , CYP1A2 , CYP1B1 , GSTM1 , GSTT2 , NQO1 , and XRCC1 . We observed significant interactions between maternal PAH exposure and SNPs on cord B[ a ]P-DNA adducts in the following genes: maternal CYP1A1 and GSTT2 , and newborn CYP1A1 and CYP1B1 . These novel findings highlight differences in maternal and newborn genetic contributions to B[ a ]P-DNA adduct formation and have the potential to identify at-risk subpopulations who are susceptible to the carcinogenic potential of B[ a ]P.

Depressed height gain of children associated with intrauterine exposure to polycyclic aromatic hydrocarbons (PAH) and heavy metals: the cohort prospective study.

Fetal exposure to environmental toxicants may program the development of children and have long-lasting health impacts. The study tested the hypothesis that depressed height gain in childhood is associated with prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and heavy metals (lead and mercury). The study sample comprised 379 children born to non-smoking mothers among whom a total of 2011 height measurements were carried out over the 9-year follow-up period. Prenatal airborne PAH exposure was assessed by personal air monitoring of the mother in the second trimester of pregnancy and heavy metals were measured in cord blood. At the age of 3 residential air monitoring was done to evaluate the level of airborne PAH, and at the age 5 the levels of heavy metals were measured in capillary blood. The effect estimates of prenatal PAH exposure on height growth over the follow-up were adjusted in the General Estimated Equation (GEE) models for a wide set of relevant covariates. Prenatal exposure to airborne PAH showed a significant negative association with height growth, which was significantly decreased by 1.1cm at PAH level above 34.7 ng/m(3) (coeff.=-1.07, p=0.040). While prenatal lead exposure was not significantly associated with height restriction, the effect of mercury was inversely related to cord blood mercury concentration above 1.2 µg/L (coeff.=-1.21, p=0.020), The observed negative impact of prenatal PAH exposure on height gain in childhood was mainly mediated by shorter birth length related to maternal PAH exposure during pregnancy. The height gain deficit associated with prenatal mercury exposure was not seen at birth, but the height growth was significantly slower at later age.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure, antioxidant levels and behavioral development of children ages 6-9.

PURPOSE: Prenatal polycyclic aromatic hydrocarbon (PAH) exposure has been shown to increase DNA adduct levels and to affect neurodevelopment. Micronutrients may modify the adverse effect of PAH on neurodevelopment. Thus, we examined if micronutrient concentrations modified the association between PAH exposure and neurodevelopmental outcomes. METHODS: 151 children from a birth cohort who had micronutrient concentrations measured in cord blood and completed the Child Behavioral Checklist (CBCL), between the ages of 6 and 9 years, were evaluated. Prenatal airborne PAH exposure was measured by personal air monitoring. The betas and 95% CI for the associations of antioxidant concentrations and PAH exposure with each of the outcomes of CBCL raw score and dichotomized standardized T-score (based on clinical cutpoints) were estimated, respectively, by multivariable poisson and logistic models. RESULTS: Children below the median for alpha-tocopherol and gamma-tocopherol concentrations, compared to those above, were more likely to have thought problems, aggressive behavior and externalizing problems (p<0.05). Lower carotenoid concentration was associated with more thought problems (MVß=0.60, p<0.001) and externalizing problems (MVß=0.13, p<0.05) for the same contrast. No statistically significant associations were observed between retinol concentrations and neurodevelopmental symptoms. Overall, no consistent patterns were observed when we examined the interaction between antioxidants (e.g., alpha-tocopherol) and PAH in relation to CBCL symptoms (e.g., internalizing and externalizing problems, p<0.05). CONCLUSIONS: Lower alpha-tocopherol, gamma-tocopherol and carotenoid levels may adversely affect healthy neurodevelopment, even after accounting for PAH exposure. Future research to confirm these findings are warranted given the importance of identifying modifiable factors for reducing harmful PAH effects.

[The influence of tocolytic drugs usage in the third trimester of pregnancy on obstetric and neonatal outcomes]. / Wplyw stosowania Ieków zapobiegajacych porodowi przedwczesnemu w III trymestrze ciazy na wyniki poloznicze oraz neonatologiczne.

INTRODUCTION: The occurrence of preterm labor is the cause of 75% of preterm births. Prematurity is the leading cause of mortality of children under four weeks of age. Tocolytic drugs are used widely in the treatment of preterm labor. The aim of this study was to assess the impact of the tocolytic therapy on obstetric and neonatal outcomes. MATERIAL AND METHODS: The prospective, cohort study included 499 pregnant women The study enrolled women who met certain criteria of age, with singleton pregnancy, having no chronic diseases. After delivery the following data were obtained: sociodemographic profile (including data on occupational activity), body height and weight before pregnancy, weight gain, duration of pregnancy, mode of delivery, obstetric complications, medications, anthropometric parameters and state of health of newborns. A group of patients treated with tocolytic drugs and a control group were identified. Then obstetric and neonatal outcomes in both groups were subjected to statistical analysis. RESULTS: There was no statistically significant difference between the two groups in terms of the following variables: mother's age, her education, professional activity of mothers in the first and second trimester of pregnancy, weight gain during pregnancy, parity, exposure to passive smoking during pregnancy, method of pregnancy termination. We found a statistically significant difference between the groups with respect to maternal weight before pregnancy (lower in the group using tocolytics), the average duration of pregnancy (lower in the group using tocolytics), the frequency of preterm birth (higher in the group using tocolytics) and neonatal anthropometric parameters and the number of points in the Apgar score at 5 minutes of age (lower in the group using tocolytics). CONCLUSIONS: Low pregestational weight is a risk factor for preterm labor. Term birth rate in pregnant women treated for preterm labor is significantly smaller compared to the general population, which may indicate low efficacy of tocolytic drugs. There was no positive correlation found between the professional activity of pregnant women and the risk of threatening preterm labor.

Gene-environment interactions on growth trajectories.

It has been suggested that children with larger brains tend to perform better on IQ tests or cognitive function tests. Prenatal head growth and head growth in infancy are two crucial periods for subsequent intelligence. Studies have shown that environmental exposure to air pollutants during pregnancy is associated with fetal growth reduction, developmental delay, and reduced IQ. Meanwhile, genetic polymorphisms may modify the effect of environment on head growth. However, studies on gene-environment or gene-gene interactions on growth trajectories have been quite limited partly due to the difficulty to quantitatively measure interactions on growth trajectories. Moreover, it is known that assessing the significance of gene-environment or gene-gene interactions on cross-sectional outcomes empirically using the permutation procedures may bring substantial errors in the tests. We proposed a score that quantitatively measures interactions on growth trajectories and developed an algorithm with a parametric bootstrap procedure to empirically assess the significance of the interactions on growth trajectories under the likelihood framework. We also derived a Wald statistic to test for interactions on growth trajectories and compared it to the proposed parametric bootstrap procedure. Through extensive simulation studies, we demonstrated the feasibility and power of the proposed testing procedures. We applied our method to a real dataset with head circumference measures from birth to age 7 on a cohort currently being conducted by the Columbia Center for Children's Environmental Health (CCCEH) in Krakow, Poland, and identified several significant gene-environment interactions on head circumference growth trajectories.

Effect of exclusive breastfeeding on the development of children's cognitive function in the Krakow prospective birth cohort study.

The main goal of the study was to assess the effect of exclusive breastfeeding on the neurodevelopment of children over a 7-year follow-up period and to test the hypothesis that the observed cognitive gain in breastfed children in the first years of life is a strong predictor of their cognitive development trajectory, which may be continued in later life. The analysis is based on data from the 7-year follow-up of 468 term babies (>36 weeks of gestation) born to non-smoking mothers participating in an ongoing prospective cohort study. The cognitive function of children was assessed by psychometric tests performed five times at regular intervals from infancy through the preschool age. The study included valid neurodevelopmental assessment of the children-443 participants were evaluated least twice; 425, three times; and 307, five times in the follow-up period. The association between the cognitive achievements of preschool age children and exclusive breastfeeding of various durations was performed using the generalized estimating equation longitudinal model, adjusted for major confounders such as maternal education, gender, parity, and weight gain in pregnancy. Children breastfed exclusively for up to 3 months had intelligence quotients (IQs) that were on average 2.1 points higher compared to the others (95% confidence interval (CI), 0.24-3.9); children breastfed for 4-6 months scored higher by 2.6 points (95% CI, 0.87-4.27); and the benefit for children breastfed even longer (>6 months) increased by 3.8 points (95% CI, 2.11-5.45). Other predictors were maternal education, gender of the child, having an older sibling, and weight gain during pregnancy. The results of the study support the WHO expert recommendations on exclusive breastfeeding for 6 months; moreover, they provide evidence that even a shorter duration of exclusive breastfeeding in early infancy produces beneficial effects on the cognitive development of children. The breastfeeding-related IQ gain observed already at the age of 1 was sustained through preschool age, and the difference in terms of IQ score between breastfed children and the reference group (mixed breastfeeding) held constant over the whole preschool period.

Methods for detecting interactions between genetic polymorphisms and prenatal environment exposure with a mother-child design.

Prenatal exposures such as polycyclic aromatic hydrocarbons and early postnatal environmental exposures are of particular concern because of the heightened susceptibility of the fetus and infant to diverse environmental pollutants. Marked inter-individual variation in response to the same level of exposure was observed in both mothers and their newborns, indicating that susceptibility might be due to genetic factors. With the mother-child pair design, existing methods developed for parent-child trio data or random sample data are either not applicable or not designed to optimally use the information. To take full advantage of this unique design, which provides partial information on genetic transmission and has both maternal and newborn outcome status collected, we developed a likelihood-based method that uses both the maternal and the newborn information together and jointly models gene-environment interactions on maternal and newborn outcomes. Through intensive simulation studies, the proposed method has demonstrated much improved power in detecting gene-environment interactions. The application on a real mother-child pair data from a study conducted in Krakow, Poland, suggested four significant gene-environment interactions after multiple comparisons adjustment.

Effects of prenatal and perinatal exposure to fine air pollutants and maternal fish consumption on the occurrence of infantile eczema.

BACKGROUND: As there is a scarcity of evidence on potential hazards and preventive factors for infantile eczema operating in the prenatal period, the main goal of this study was to assess the role of prenatal exposure to fine particulate matter and environmental tobacco smoke (ETS) in the occurrence of infant eczema jointly with the possible modulating effect of maternal fish consumption. METHODS: The study sample consisted of 469 women enrolled during pregnancy, who gave birth to term babies (>36 weeks of gestation). Among all pregnant women recruited, personal measurements of fine particulate matter (PM2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, every 3 months in the first year of the newborn's life, a detailed, standardized, face-to-face interview was administered to each mother, in the process of which a trained interviewer recorded any history of infantile eczema and data on potential environmental hazards. The estimated risk of eczema related to higher prenatal exposure to fine particulate matter (PM2.5 > 53.0 µg/m³) and postnatal ETS as well as the protective effect of maternal fish intake were adjusted for potential confounders in a multivariable logistic regression model. RESULTS: While the separate effects of higher prenatal PM2.5 and postnatal ETS exposure were not statistically significant, their joint effect appeared to have a significant influence on the occurrence of infantile eczema [odds ratio 2.39, 95% confidence interval (CI) 1.10-5.18]. With maternal fish intake of more than 205 g/week, the risk of eczema decreased by 43% (odds ratio 0.57, 95% CI 0.35-0.93). The incidence rate ratio (IRR) for eczema symptoms, estimated from the Poisson regression model, was increased with both higher exposure to prenatal PM2.5 and postnatal ETS (IRR 1.55, 95% CI 0.99-2.44) and in children of atopic mothers (IRR 1.35, 95% CI 1.04-1.75) but was lower in girls (IRR 0.78, 95% CI 0.61-1.00). The observed preventive effect of fish consumption on the frequency of eczema symptoms was consistent with the results of the logistic analysis (IRR 0.72, 95% CI 0.52-0.99). CONCLUSIONS: The findings indicate that higher prenatal exposure to fine particulate matter combined with postnatal exposure to ETS may increase the risk of infant eczema, while maternal fish intake during pregnancy may reduce the risk of infantile eczema.

Intrauterine exposure to lead may enhance sensitization to common inhalant allergens in early childhood: a prospective prebirth cohort study.

BACKGROUND: Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines. OBJECTIVES: The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood. MATERIAL AND METHODS: The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child's gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts. RESULTS AND CONCLUSION: In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood.

Effect of gene-environment Interactions on mental development in African American, Dominican, and Caucasian mothers and newborns.

The health impact of environmental toxins has gained increasing recognition over the years. Polycyclic aromatic hydrocarbons (PAHs) and environmental tobacco smoke (ETS) are known to affect nervous system development in children, but no studies have investigated how polymorphisms in PAH metabolic genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of non-smoking African American and Dominican mothers and children in New York City and of Caucasian mothers and children in Krakow, Poland, we explored the effect of gene-PAH interaction on child mental development index (MDI). Genes known to play important roles in the metabolic activation or detoxification of PAHs were selected. Genetic variations in these genes could influence susceptibility to adverse effects of PAHs in polluted air. We explored the effects of interactions between prenatal PAH exposure and 21 polymorphisms or haplotypes in these genes on MDI at 12, 24, and 36 months among 547 newborns and 806 mothers from three different ethnic groups. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene.

Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze. Prospective birth cohort study in 4-year olds.

The main goal of the study was to determine the relationship between prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured by PAH-DNA adducts in umbilical cord blood and early wheeze. The level of PAH-DNA adducts in the cord blood is assumed to reflect the cumulative dose of PAHs absorbed by the foetus over the prenatal period. The effect of prenatal PAH exposure on respiratory health measured by the incidence rate ratio (IRR) for the number of wheezing days in the subsequent 4 yr follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM(2.5)), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity and mould/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18-35 yr of age and free from chronic diseases, who were recruited from ambulatory prenatal clinics in the first or second trimester of pregnancy. The number of wheezing days during the first 2 yr of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52-1.88), prenatal particulate matter (PM(2.5)) level dichotomized by the median (IRR = 1.38; 95%CI: 1.25-1.51), maternal atopy (IRR = 1.43; 95%CI: 1.29-1.58), mouldy/damp house (IRR = 1.43; 95%CI: 1.27-1.61). The level of maternal education and maternal age at delivery was inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM(2.5)) was not observed at ages 3 or 4 yrs. Although the frequency of wheezing at ages 3 or 4 was no longer associated with prenatal exposure to PAHs and PM(2.5), its occurrence depended on the presence of wheezing in the first 2 yr of life, which nearly tripled the risk of wheezing in later life. In conclusion, the findings may suggest that driving force for early wheezing (<24 months of age) is different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM(2.5) exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze.

Early wheezing phenotypes and cognitive development of 3-yr-olds. Community-recruited birth cohort study.

The main purpose of the study was to answer the question whether young children without clinical diagnosis of asthma but experiencing early wheezing disorders and therefore being at high risk of developing asthma may have cognitive deficits. In the ongoing birth cohort study wheezing symptoms were recorded postpartum over two first years of age and subsequently cognitive status of children at the age of 3 yr was assessed with the Bayley Mental Development Index (MDI). In the statistical analysis a wide range of modifying and confounding factors (maternal education, gender of children, prenatal exposure to lead and environmental tobacco smoke (ETS) were considered to assess the independent effect of early wheezing phenotypes on cognitive development of children. The MDI score correlated inversely with the number of wheezing days recorded over 24 months (r = -0.13, p = 0.007), lead cord blood concentration (r = -0.12, p = -0.02), number of siblings (r = -0.17, p = 0.0006) and the number of cigarettes smoked daily by other household members at home over the pregnancy period (r = -0.18, p = 0.0002). While the children who experienced wheezing over the first year of age showed deficit of 2 MDI scores (beta coeff. = -2.31, 95%CI: -4.63 to 0.02), those with persistent wheezing had the score deficit of 4 points (beta coeff. = -4.41, 95%CI: -8.27 to -0.55). To our knowledge, it is the first report in the iterature showing that early wheezing is associated the cognitive deficit in a community-recruited very young children. Observed cognitive deficit in early wheezers may be caused by RSV infections or can be related to lower lung function attributed to persistent wheezing, which reducing oxygen supply would affect rapidly developing brain.

Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non-smoking mothers.

Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM(2.5)), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM(2.5) were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow-up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)) and forced expiratory volume in 0.5 s (FEV(0.5)). There were 176 children of non-smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM(2.5) exposure (beta coefficient = -91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV(1) level in children was inversely correlated with prenatal exposure to PM(2.5), and the average FEV(1) deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM(2.5) exposure on FEV(0.5) was proportionally weaker (-72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow-up. The findings showed that significant lung function deficits in early childhood are associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.

Higher fish consumption in pregnancy may confer protection against the harmful effect of prenatal exposure to fine particulate matter.

BACKGROUND/AIM: The objective of this study was to assess a hypothesized beneficial effect of fish consumption during the last trimester of pregnancy on adverse birth outcomes resulting from prenatal exposure to fine air particulate matter. METHODS: The cohort consisted of 481 nonsmoking women with singleton pregnancies, of 18-35 years of age, who gave birth at term. All recruited women were asked about their usual diet over the period of pregnancy. Measurements of particulate matter less than 2.5 mum in size (PM(2.5)) were carried out by personal air monitoring over 48 h during the second trimester of pregnancy. The effect of PM(2.5) and fish intake during gestation on the birth weight of the babies was estimated from multivariable linear regression models, which beside the main independent variables considered a set of potential confounding factors such as the size of the mother (height, prepregnancy weight), maternal education, parity, the gender of the child, gestational age and the season of birth. RESULTS: The study showed that the adjusted birth weight was significantly lower in newborns whose mothers were exposed to particulate matter greater than 46.3 microg/m3 (beta coefficient = -97.02, p = 0.032). Regression analysis stratified by the level of maternal fish consumption (in tertiles) showed that the deficit in birth weight amounted to 133.26 g (p = 0.052) in newborns whose mothers reported low fish intake (<91 g/week). The birth weight deficit in newborns whose mothers reported medium (91-205 g/week) or higher fish intake (>205 g/week) was insignificant. The interaction term between PM(2.5) and fish intake levels was also insignificant (beta = -107,35, p = 0.215). Neither gestational age nor birth weight correlated with maternal fish consumption. CONCLUSIONS: The results suggest that a higher consumption of fish by women during pregnancy may reduce the risk of adverse effects of prenatal exposure to toxicants and highlight the fact that a full assessment of adverse birth outcomes resulting from prenatal exposure to ambient hazards should consider maternal nutrition during pregnancy.

Very low prenatal exposure to lead and mental development of children in infancy and early childhood: Krakow prospective cohort study.

BACKGROUND: The primary purpose of the study was to establish a possible association between very low levels of prenatal exposure to lead and mental development of children at 12, 24 and 36 months of age. METHODS: The study sample consisted of 444 children born to mothers who attended ambulatory prenatal clinics in Krakow inner city in the first and second trimesters of pregnancy. We assessed exposure to lead by the cord blood lead measurements, and mental development in infancy and early childhood using the Bayley Mental Development Index (MDI). The relationship between prenatal lead exposure and MDI scores at each follow-up period was evaluated with linear multivariate regression. To test the overall effect of maternal exposure to lead during pregnancy on the Bayley test scores at 12, 24 and 36 months of age, we used the generalized estimating equations (GEE) longitudinal panel model as well. RESULTS: The median lead level in cord blood was 1.23 microg/dl, in the range of 0.44-6.90 microg/dl. An adverse effect of prenatal lead exposure (log-transformed lead concentrations) on MDI scores at 12 months of age was of border significance (beta = -5.42, 95% CI: -11.19 to 0.35). Subsequent testing of children at 24 months of age showed a significant inverse association of mental function and lead exposure (beta = -7.65, 95% CI: -14.68 to -0.62). A significant deficit in cognitive function due to prenatal lead exposure was also confirmed at 36 months of age (beta = -6.72, 95% CI: -12.5 to -0.89). The GEE panel model showed that the average deficit in the cognitive development attributable to lead exposure over 3 years was also significant (beta = -6.62, 95% CI: -1.52 to -1.72). Mental function scores of girls were better than boys, and the effect of maternal education remained strongly significant in relation to mental function of 3-year-olds. CONCLUSION: The results of the study demonstrate that the neurotoxic impact of very low levels of prenatal lead exposure (below 5 microg/dl) may occur in infants and very young children, and suggest a revision of established health guidelines for prenatal lead exposure criteria.

Gender differences in fetal growth of newborns exposed prenatally to airborne fine particulate matter.

Our primary purpose was to assess sex-specific fetal growth reduction in newborns exposed prenatally to fine particulate matter. Only women 18-35 years of age, who claimed to be non-smokers, with singleton pregnancies, without illicit drug use and HIV infection, free from chronic diseases were eligible for the study. A total of 481 enrolled pregnant women who gave birth between 37 and 43 weeks of gestation were included in the study. Prenatal personal exposure to fine particles over 48 h during the second trimester was measured using personal monitors. To evaluate the relationship between the level of PM(2.5) measured over 48 h in the second trimester of pregnancy with those in the first and the third trimesters, a series of repeated measurements in each trimester was carried out in a random subsample of 85 pregnant women. We assessed the effect of PM(2.5) exposure on the birth outcomes (weight, length and head circumference at birth) by multivariable regression models, controlling for potential confounders (maternal education, gestational age, parity, maternal height and prepregnancy weight, sex of infant, prenatal environmental tobacco smoke, and season of birth). Birth outcomes were associated positively with gestational age, parity, maternal height and prepregnancy weight, but negatively with the level of prenatal PM(2.5) exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30 microg/m3, i.e., from 25th percentile (23.4 microg/m3) to 75th percentile (53.1 microg/m3) brought about an average birth weight deficit of 97.2g (95% CI: -201, 6.6) and length at birth of 0.7 cm (95% CI: -1.36, -0.04). The corresponding exposure lead to birth weight deficit in male newborns of 189 g (95% CI: -34.2, -343) in comparison to 17g in female newborns; the deficit of length at birth in male infants amounted to 1.1cm (95% CI: -0.11, -2.04). We found a significant interrelationship between self-reported ETS and PM(2.5), however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM(2.5) and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM(2.5). Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM(2.5) exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM(2.5) exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.

An apple a day may hold colorectal cancer at bay: recent evidence from a case-control study.

Environmental factors play an important role in the etiology of colorectal cancer, the second-most common malignancy in both genders in developed countries. Evidence has shown that potential cancer-inducing oxidative damage might be prevented or restricted largely by the presence of dietary antioxidants of plant origin, such as fruits or vegetables. The protective antioxidant effect of fruits and vegetables has been attributed to flavonoids, a major class of phytochemicals naturally occurring in fruits, vegetables, and various foods of plant origin. Yet, epidemiologic cohort studies relating flavonoid intake to risk of colorectal cancer have been sparse and inconclusive. Apples are a rich source of flavonoids and have the second highest level of antioxidant power among all fruits, with peels having a stronger antioxidant activity than apple flesh. A recent reanalysis of several case-control studies in Italy demonstrated a consistent inverse association between apple consumption and the risk of various cancers, and among them ofcolorectal cancer. Here we assessed the potential protective impact of apples on risk of colorectal cancer in the course of a recently performed hospital-based case-control study in a country with dietary habits very different from those of Mediterranean region. The results showed that highest risk of colorectal cancer was among older persons and those who were residents of villages or small towns. The risk of colorectal cancer was inversely correlated with daily number of apple servings, but the most significant reductions of OR estimates were observed for an intake one or more apple servings daily (OR = 0.37, 95% CI: 0.15-0.91). No other fruit was significantly associated with altering the risk of colorectal cancer.

Fetal exposure to secondhand tobacco smoke assessed by maternal self-reports and cord blood cotinine: prospective cohort study in Krakow.

OBJECTIVES: While the validity of self-reported smoking habits is generally judged as satisfactory, objective markers of secondhand smoke (SHS) exposure may be more useful in validating the causal links between prenatal SHS and health effects. The cohort study in Krakow provided an opportunity for comparative assessment of fetal exposure to SHS based upon questionnaires and cord blood cotinine measurements. METHODS: The study sample included 467 newborns born to women recruited in the first and second trimester of pregnancy. To compare the validity of self-reported SHS and cord blood cotinine levels in assessing the association between fetal passive smoking and health effects of newborns, we separately examined the regression coefficients of birthweight on self-reported number of cigarettes smoked by other household members during the entire pregnancy and cord blood cotinine levels. RESULTS: In the non-exposed newborns the geometric mean of cord blood cotinine was 0.077 ng/ml and was significantly lower than in newborns with a maternal report of SHS. Cord cotinine levels were more highly correlated with a self-reported number of cigarettes smoked daily at home in the third trimester of pregnancy. The two measures of SHS (number of cigarettes and number of hours of daily exposure) were equally well correlated with cord blood cotinine levels. Using cotinine as the exposure variable, overall the association was not significant; but among the subgroup with cord cotinine levels above the median (> or =0.083 ng/ml), the association with birthweight was significant (beta coefficient = -113.65, P = 0.041). CONCLUSION: The study provides evidence that the assessment of fetal SHS exposure based on cord blood cotinine produced better estimates of the association between exposure and birth outcomes.

[Nutritional status of pregnant women and birth outcome]. / Stan odzywienia kobiet ciezarnych a cechy rozwoju somatycznego noworodków.

OBJECTIVE: The aim of the study was to determine whether nutritional status of pregnant women influences the birth outcome. METHODS: A prospective study, conducted in Krakow, in 382 non-smoking, no obese pregnant women between the ages of 18 - 35. The course of pregnancy was uncomplicated, finished with natural labor, in biological time limits. The impact of mother's nutritional status before pregnancy and weight gain on newborns weight, length and head circumference was estimated by multivariate linear regression. RESULTS: The infant birth weight depended on mothers nutritional status before pregnancy and was lower in the group of underweight subjects (3381.6 g vs. 3479.9 g, p = 0.022). Women with low increase in body mass during pregnancy delivered newborns with lower anthropometrics parameters. The increase in body weight of one category resulted in statistically significant increase of birth weight by 140.9 g, increase of length by 0.51 cm and in head circumference by 0.27 cm. CONCLUSIONS: Increase in body mass during pregnancy is particularly important in the group of women underweight before pregnancy. Change of nutritional habits before and in the course of pregnancy may have beneficial effects for intrauterine fetal development.

Assessment of interactions between PAH exposure and genetic polymorphisms on PAH-DNA adducts in African American, Dominican, and Caucasian mothers and newborns.

Polycyclic aromatic hydrocarbons (PAH) are widespread pollutants commonly found in air, food, and drinking water. Benzo[a]pyrene is a well-studied representative PAH found in air from fossil fuel combustion and a transplacental carcinogen experimentally. PAHs bind covalently to DNA to form DNA adducts, an indicator of DNA damage, and an informative biomarker of potential cancer risk. Associations between PAH-DNA adduct levels and both cancer risk and developmental deficits have been seen in previous experimental and epidemiologic studies. Several genes have been shown to play an important role in the metabolic activation or detoxification of PAHs, including the cytochrome P450 genes CYP1A1 and CYP1B1 and the glutathione S-transferase (GST) genes GSTM1, and GSTT2. Genetic variation in these genes could influence susceptibility to adverse effects of PAHs in polluted air. Here, we have explored interactions between prenatal PAH exposure and 17 polymorphisms in these genes (rs2198843, rs1456432, rs4646903, rs4646421, rs2606345, rs7495708, rs2472299, rs162549, rs1056837, rs1056836, rs162560, rs10012, rs2617266, rs2719, rs1622002, rs140194, and gene deletion GSTM1-02) and haplotypes on PAH-DNA adducts in cord blood of 547 newborns and in maternal blood of 806 mothers from three different self-described ethnic groups: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interactions (p < 0.05) were observed between certain genetic polymorphisms and CYP1A1 haplotype and PAHs in mothers and their newborns in the three ethnic groups. However, with our limited sample size, the current findings are suggestive only, warranting further study.