Elzbieta Mroz

Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Children's Intelligence at 5 Years of Age in a Prospective Cohort Study in Poland

Background In this prospective cohort study of Caucasian mothers and children in Krakow, Poland, we evaluated the role of prenatal exposure to urban air pollutants in the pathogenesis of neurobehavioral disorders. Objectives The objective of this study was to investigate the relationship between prenatal polycyclic aromatic hydrocarbon (PAH) exposure and child intelligence at 5 years of age, controlling for potential confounders suspected to play a role in neurodevelopment. Methods A cohort of pregnant, healthy, nonsmoking women was enrolled in Krakow, Poland, between 2001 and 2006. During pregnancy, participants were invited to complete a questionnaire and undergo 48-hr personal air monitoring to estimate their babies’ exposure, and to provide a blood sample and/or a cord blood sample at the time of delivery. Two hundred fourteen children were followed through 5 years of age, when their nonverbal reasoning ability was assessed using the Raven Coloured Progressive Matrices (RCPM). Results We found that higher (above the median of 17.96 ng/m3) prenatal exposure to airborne PAHs (range, 1.8–272.2 ng/m3) was associated with decreased RCPM scores at 5 years of age, after adjusting for potential confounding variables (n = 214). Further adjusting for maternal intelligence, lead, or dietary PAHs did not alter this association. The reduction in RCPM score associated with high airborne PAH exposure corresponded to an estimated average decrease of 3.8 IQ points. Conclusions These results suggest that prenatal exposure to airborne PAHs adversely affects children’s cognitive development by 5 years of age, with potential implications for school performance. They are consistent with a recent finding in a parallel cohort in New York City.

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 μg/dl, in the range of 0.44–6.90 μg/dl. An adverse effect of prenatal lead exposure (log-transformed lead concentrations) on MDI scores at 12 months of age was of border significance (β = –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 (β = –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 (β = –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 (β = –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 μg/dl) may occur in infants and very young children, and suggest a revision of established health guidelines for prenatal lead exposure criteria.

GENDER SPECIFIC DIFFERENCES IN NEURODEVELOPMENTAL EFFECTS OF PRENATAL EXPOSURE TO VERY LOW-LEAD LEVELS: THE PROSPECTIVE COHORT STUDY IN THREE-YEAR OLDS

UNLABELLED The primary purpose of this study was to assess the relationship between very low-level of prenatal lead exposure measured in the cord blood (<5 microg/dL) and possible gender-specific cognitive deficits in the course of the first three years of life. The accumulated lead dose in infants over the pregnancy period was measured by the cord blood lead level (BLL) and cognitive deficits were assessed by the Bayley Mental Development Index (MDI). The study sample consisted of 457 children born to non-smoking women living in the inner city and the outlying residential areas of Krakow. The relationship between prenatal lead exposure and MDI scores measured at 12, 24 and 36 months of age and adjusted to a set of important covariates (gender of child, maternal education, parity, breastfeeding, prenatal and postnatal environmental tobacco smoke) was evaluated with linear multivariate regression, and the Generalized Estimating Equations (GEE) longitudinal panel model. The median of lead level in cord blood was 1.21 microg/dL with the range of values from 0.44 to 4.60 microg/dL. Neither prenatal BLL (dichotomized by median) nor other covariates affected MDI score at 12 months of age. Subsequent testing of children at 24 months of age showed a borderline significant inverse association of lead exposure and mental function (beta coefficient=-2.42, 95%CI: -4.90 to 0.03), but the interaction term (BLL x male gender) was not significant. At 36 months, prenatal lead exposure was inversely and significantly associated with cognitive function in boys (Spearman correlation coefficient=-0.239, p=0.0007) but not girls (r=-0.058, p=0.432) and the interaction between BLL and male gender was significant (beta coefficient=-4.46; 95%CI: -8.28 to -0.63). Adjusted estimates of MDI deficit in boys at 36 months confirmed very strong negative impact of prenatal lead exposure (BLL>1.67 microg/dL) compared with the lowest quartile of exposure (beta coefficient=-6.2, p=0.002), but the effect in girls was insignificant (beta coefficient=-0.74, p=0.720). The average deficit of cognitive function in the total sample over the first three years of life (GEE model) associated with higher prenatal lead exposure was also significant (beta coefficient=-3.00; 95%CI: -5.22 to -0.70). Beside prenatal lead exposure, presence of older siblings at home and prenatal environmental tobacco smoke had a negative impact on MDI score. Better maternal education showed a strong beneficial effect on the cognitive development of children. CONCLUSION the study suggests that there might be no threshold for lead toxicity in children and provides evidence that 3-year old boys are more susceptible than girls to prenatal very low lead exposure. The results of the study should persuade policy makers to consider gender-related susceptibility to lead and possibly to other toxic hazards in setting environmental protection guidelines. To determine whether the cognitive deficit documented in this study persists to older ages, the follow-up of the children over the next several years is to be carried out.

Estimating Individual-Level Exposure to Airborne Polycyclic Aromatic Hydrocarbons throughout the Gestational Period Based on Personal, Indoor, and Outdoor Monitoring

Objectives Current understanding on health effects of long-term polycyclic aromatic hydrocarbon (PAH) exposure is limited by lack of data on time-varying nature of the pollutants at an individual level. In a cohort of pregnant women in Krakow, Poland, we examined the contribution of temporal, spatial, and behavioral factors to prenatal exposure to airborne PAHs within each trimester and developed a predictive model of PAH exposure over the entire gestational period. Methods We monitored nonsmoking pregnant women (n = 341) for their personal exposure to pyrene and eight carcinogenic PAHs—benz[a]anthracene, chrysene/isochrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene [B(a)P], indeno[1,2,3-c,d]pyrene, dibenz[a,h]anthracene, and benzo[g,h,i]perylene—during their second trimester for a consecutive 48-hr period. In a subset (n = 78), we monitored indoor and outdoor levels simultaneously with the personal monitoring during the second trimester with an identical monitor. The subset of women was also monitored for personal exposure for a 48-hr period during each trimester. We repeatedly administered a questionnaire on health history, lifestyle, and home environment. Results The observed personal, indoor, and outdoor B(a)P levels we observed in Krakow far exceed the recommended Swedish guideline value for B(a)P of 0.1 ng/m3. Based on simultaneously monitored levels, the outdoor PAH level alone accounts for 93% of total variability in personal exposure during the heating season. Living near the Krakow bus depot, a crossroad, and the city center and time spent outdoors or commuting were not associated with higher personal exposure. During the nonheating season only, a 1-hr increase in environmental tobacco smoke (ETS) exposure was associated with a 10–16% increase in personal exposure to the nine measured PAHs. A 1°C decrease in ambient temperature was associated with a 3–5% increase in exposure to benz[a]anthracene, benzo[k]fluoranthene, and dibenz[a,h]anthracene, after accounting for the outdoor concentration. A random effects model demonstrated that mean personal exposure at a given gestational period depends on the season, residence location, and ETS. Conclusion Considering that most women reported spending < 3 hr/day outdoors, most women in the study were exposed to outdoor-originating PAHs within the indoor setting. Cross-sectional, longitudinal monitoring supplemented with questionnaire data allowed development of a gestation-length model of individual-level exposure with high precision and validity. These results are generalizable to other nonsmoking pregnant women in similar exposure settings and support reduction of exposure to protect the developing fetus.

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.

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

Jedrychowski WA, Perera FP, Maugeri U, Mrozek‐Budzyn D, Mroz E, Klimaszewska‐Rembiasz M, Flak E, Edwards S, Spengler J, Jacek R, Sowa A. Intrauterine exposure to polycyclic aromatic hydrocarbons, fine particulate matter and early wheeze. Prospective birth cohort study in 4‐year olds.
Pediatr Allergy Immunol 2010: 21: e723–e732.
© 2010 John Wiley & Sons A/S

Intrauterine exposure to fine particulate matter as a risk factor for increased susceptibility to acute broncho-pulmonary infections in early childhood

Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood. The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, childrens sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR=2.44, 95%CI: 1.12-5.36). In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20μg/m(3) for the 24-h mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.

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.

Impact of barbecued meat consumed in pregnancy on birth outcomes accounting for personal prenatal exposure to airborne polycyclic aromatic hydrocarbons: Birth cohort study in Poland

OBJECTIVE We previously reported an association between prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH) and lower birth weight, birth length, and head circumference. The main goal of the present analysis was to assess the possible impact of coexposure to PAH-containing barbecued meat consumed during pregnancy on birth outcomes. MATERIALS AND METHODS The birth cohort consisted of 432 pregnant women who gave birth at term (>36 wk of gestation). Only non-smoking women with singleton pregnancies, 18-35 y of age, and who were free from chronic diseases such as diabetes and hypertension, were included in the study. Detailed information on diet over pregnancy was collected through interviews and the measurement of exposure to airborne PAHs was carried out by personal air monitoring during the second trimester of pregnancy. The effect of barbecued meat consumption on birth outcomes (birth weight, length, and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, childs sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy), and prenatal environmental tobacco smoke. RESULTS The multivariable regression model showed a significant deficit in birth weight associated with barbecued meat consumption in pregnancy (coeff = -106.0 g; 95%CI: -293.3, -35.8). The effect of exposure to airborne PAHs was about the same magnitude order (coeff. = -164.6 g; 95%CI: -172.3, -34.7). Combined effect of both sources of exposure amounted to birth weight deficit of 214.3 g (95%CI: -419.0, -9.6). Regression models performed for birth length and head circumference showed similar trends but the estimated effects were of borderline significance level. As the intake of barbecued meat did not affect the duration of pregnancy, the reduced birth weight could not have been mediated by a shortened gestation period. CONCLUSION In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.

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 childrens respiratory symptoms every 3 months in the childs 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.