Airborne polycyclic aromatic hydrocarbons (PAHs) are pollutants generated by combustion of fossil fuel and other organic material. Both prenatal PAH exposure and maternal psychological distress during pregnancy have each been associated with neurodevelopmental problems in children. The goal was to evaluate potential interactions between prenatal exposure to airborne PAHs and maternal psychological distress during pregnancy on subsequent behavioral problems in children.
In a longitudinal birth cohort study, 248 children of nonsmoking white women in the coal-burning region of Krakow, Poland, were followed from in utero until age 9. Prenatal PAH exposure was measured by personal air monitoring during pregnancy, maternal demoralization during pregnancy by the Psychiatric Epidemiology Research Instrument–Demoralization, and child behavior by the Child Behavior Checklist.
Significant interactions between maternal demoralization and PAH exposure (high versus low) were identified for symptoms of anxious/depressed, withdrawn/depressed, social problems, aggressive behavior, internalizing problems, and externalizing problems. The effects of demoralization on syndromes of anxious/depressed, withdrawn/depressed, rule-breaking, aggressive behavior, and the composite internalizing and externalizing scores were seen only in conjunction with high PAH exposure. Fewer significant effects with weaker effect sizes were observed in the low-PAH-exposure group.
Maternal demoralization during pregnancy appears to have a greater effect on child neurobehavioral development among children who experienced high prenatal PAH exposure. The results provide the first evidence of an interaction between prenatal exposure to maternal demoralization and air pollution on child neurobehavioral development, indicating the need for a multifaceted approach to the prevention of developmental problems in children.
prenatal; PAH; air pollution; child behavior; maternal psychological distress; demoralization
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 PM2.5 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 PM2.5 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 PM2.5 exposure. Overall average increase in gestational period of prenatal exposure to fine particles by about 30 μg/m3, i.e., from 25th percentile (23.4 μg/m3) to 75th percentile (53.1 μg/m3) brought about an average birth weight deficit of 97.2 g (95% CI: −201, 6.6) and length at birth of 0.7cm (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 17 g in female newborns; the deficit of length at birth in male infants amounted to 1.1 cm (95% CI: −0.11, −2.04). We found a significant interrelationship between self-reported ETS and PM2.5, however, none of the models showed a significant interaction of both variables. The joint effect of various levels of PM2.5 and ETS on birth outcomes showed the significant deficit only for the categories of exposure with higher component of PM2.5. Concluding, the results of the study suggest that observed deficits in birth outcomes are rather attributable to prenatal PM2.5 exposure and not to environmental tobacco smoke. The study also provided evidence that male fetuses are more sensitive to prenatal PM2.5 exposure and this should persuade policy makers to consider birth outcomes by gender separately while setting air pollution guidelines.
Cohort study; Prenatal exposure; Air pollutants; Fine particles; Gender; Fetal growth deficits
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 “epigenetic 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 (PM2.5 ), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study personal measurements of PM2.5 was performed over 48 hours in the second trimester of pregnancy. After delivery, infants were followed over five years and the interviewers visited participants at their homes to record children’s respiratory symptoms every three months in the child’s first two years of life and every 6 months later. In the fifth year of the follow-up, children were invited for standard lung function testing and quantified by FVC, FEV1 and FEV05 levels. Material consisted of 176 children of nonsmoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression model showed a significant deficit of FVC at the highest quartile of PM2.5 exposure (beta coefficient = − 91.9 , P = 0.008), after adjustment for covariates (age, gender, birth weight, height and wheezing). Also FEV1 level in children was inversely correlated with prenatal exposure to PM2.5, and the average FEV1 deficit amounted to 87.7 ml (P = 0.008) at the higher level of exposure. Although the effect of PM2.5 exposure on FEV05 was proportionally weaker (−72.7, P = 0.026) it was significant as well. 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 is associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth.
prenatal exposure; air pollution; birth cohort; lung function; preschool children
In the last decade, the neurologic effects of various air pollutants have been the focus of increasing attention. The main purpose of this study was to assess the potential impact of early childhood exposure to indoor molds on the subsequent cognitive function of 6-year old children. The results of this study are based on the six-year follow-up of 277 babies born at term to mothers participating in a prospective cohort study in Krakow, Poland. The study participants are all non-smoking pregnant women who were free of chronic diseases such as diabetes and hypertension.
The presence of visible mold patches on indoor walls was monitored at regular time intervals over gestation and after birth up to the age of five. The Wechsler Intelligence Scale for Children (WISC-R) was administered to children at age 6. The exposure effect of living in mold-contaminated homes on the IQ scores of children was adjusted for major confounders, known to be important for the cognitive development of children such as maternal education, the child’s gender, breastfeeding practices in infancy, the presence of older siblings and the prenatal exposure to lead and environmental tobacco smoke (ETS).
The adjusted IQ deficit attributed to longer exposures to indoor molds (> 2 years) was significantly lower on the IQ scale (beta coeff. = −9.16, 95%CI: −15.21, −3.10) and tripled the risk of low IQ scoring (OR= 3.53; 95%CI: 1.11 – 11.27) compared with references. While maternal education (beta coeff. = 0.61, 95%CI: 0.05, 1.17) and breastfeeding (beta coeff. = 4.0; 95%CI: 0.84, 7.17) showed a significant positive impact on cognitive function, prenatal ETS exposure (beta coeff. = −0.41; 95%CI: −0.79, −0.03) and the presence of older siblings (beta coefficient= −3.43; 95%CI: −5.67, −1.20) were associated with poorer cognitive function in children.
In conclusion, the results of this study draw attention to the harmful effect of early postnatal exposure to indoor molds on children cognitive development and provide additional evidence on the role of environmental determinants in human cognitive development.
cognitive function; children; exposure to molds; breastfeeding; 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 seven-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 seven-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 5 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 duration was performed using the GEE (General Estimation 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 IQs that were on average 2.1 points higher compared to the others (95%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 six 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.
breastfeeding; cognitive function in early childhood; prospective birth cohort study
In a birth cohort study, we have assessed the dose-response relationship between individual measurements of prenatal airborne PAH exposure and specific PAH-DNA adducts in cord blood adjusted for maternal blood adducts and season of birth. The study uses data from an earlier established birth cohort of children in Krakow. The final analysis included 362 pregnant women who gave birth to term babies and had complete data on personal exposure in the second trimester of pregnancy to eight airborne polycyclic aromatic hydrocarbons (PAH) including benzo[a]pyrene (B[a]P), as well as DNA adducts, both in maternal and cord blood.
The relation between cord blood PAH-DNA adducts and airborne prenatal PAH exposure was non-linear. While cord blood PAH-DNA adducts were significantly associated with the B[a]P exposure categorized by tertiles (nonparametric trend z = 3.50, p < 0.001), the relationship between B[a]P and maternal blood adducts was insignificant (z = 1.63, p = 0.103). Based on the multivariable linear regression model we estimated the effect of the prenatal airborne B[a]P on the level of cord blood adducts. In total, 14.8% of cord blood adducts variance was attributed to the level of maternal adducts and 3% to a higher prenatal B[a] exposure above 5.70 ng/m3. The calculated fetal/maternal blood adducts ratio (FMR) linearly increased with the B[a]P exposure (z = 1.99, p = 0.047) and was highest at B[a]P concentrations exceeding 5.70 ng/m3.
In conclusion, the results support other findings that transplacental exposure to B[a[P from maternal inhalation produces DNA damage in the developing fetus. It also confirms the heightened fetal susceptibility to prenatal PAH exposure that should be a matter of public health concern particularly in the highly polluted areas because DNA adducts represent a pro-carcinogenic alteration in DNA The continuation of this birth cohort study will assess the possible health effects of fetal DNA damage on health of children and help in establishing new protective guidelines for newborns.
prenatal exposure; polycyclic aromatic hydrocarbons; biomarkers of exposure; PAH-DNA adducts; birth cohort study
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 µg/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 µg/dL with the range of values from 0.44 to 4.60 µg/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 coeff. = −2.42, 95%CI: −4.90 to 0.03), but the interaction term (BLL × 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 coeff. = − 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>1.67µg/dL) compared with the lowest quartile of exposure (beta coeff. = −6.2, p = 0.002), but the effect in girls was insignificant (beta coeff = −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.
prenatal lead exposure; cognitive function; early childhood; prospective birth cohort study
The purpose of the study was to check the hypothesis that early wheezing as reported by mothers would be associated with reduced lung function in 4-year-olds. Study participants were recruited prenatally, as part of a prospective cohort study on the respiratory health of young children exposed to various ambient air pollutants. After delivery, infants were followed over four years and the interviewers visited participants at their home to record respiratory symptoms every three months in the child’s first two years of life and every 6 months in the third and fourth years. In the fourth year of follow-up, children were invited for standard lung function testing by spirometry quantified by FVC, FEV1 and FEV05 levels. Out of 258 children attending spirometry testing 139 performed at least two acceptable exhalation efforts. Cohort children with acceptable spirometric measurements did not differ with respect to wheezing experience and exposure characteristics from those without. The study shows that episodic wheeze was reported in 28.1% of 4-year-olds, 6.5% had transient wheeze and 4.3% had recurrent wheeze. There was an increased frequency of wheezing symptoms and their duration in transient and recurrent wheezers. Adjusted multivariable regression models for gender and height showed that children who reported more than 2 episodes of wheezing at any point over the follow-up had FVC values lower by 120.5 mL (p = 0.016) and FEV1 values lower by 98.3 mL (p = 0.034) compared to those who did not report any wheezing; children experiencing more than 10 wheezing days by age 4 showed FVC deficit of 87.4 mL (p = 0.034) and FEV1 values of 65.7 mL (p = 0.066) The ratios of FEV1/FVC% and FEV05/FVC% were neither associated with wheezing episodes nor wheezing days. In recurrent wheezers lung function decrement amounted to 207 mL of FVC, 175 mL of FEV1 and 104 mL of FEV05. In conclusion, our findings show that wheezing experience during early postnatal life may be associated with lung function deficit of restrictive character in preschool children and detailed history of wheeze in early postnatal life, even though not physician-confirmed, may help define the high risk group of children for poor lung function testing.
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 fetus 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 four year follow-up was adjusted for potential confounding factors such as personal prenatal exposure to fine particulate matter (PM2.5), environmental tobacco smoke (ETS), gender of child, maternal characteristics (age, education and atopy), parity, and mold/dampness in the home. The study sample includes 339 newborns of non-smoking mothers 18-35 years 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 two years of life was positively associated with prenatal level of PAH-DNA adducts (IRR = 1.69, 95%CI = 1.52 – 1.88), prenatal particulate matter (PM2.5) 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), moldy/damp house (IRR = 1.43; 95%CI: 1.27 – 1.61). The level of maternal education and maternal age at delivery were inversely associated with the IRRs for wheeze. The significant association between frequency of wheeze and the level of prenatal environmental hazards (PAHs and PM2.5) was not observed at ages 3 or 4 years. Although the frequency of wheezing at ages 3 or 4 years was no longer associated with prenatal exposure to PAHs and PM2.5, its occurrence depended on the presence of wheezing in the first two years 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) are different to those leading to later onset of wheeze. As we reported no synergistic effects between prenatal PAH (measured by PAH-DNA adducts) and PM2.5 exposures on early wheeze, this suggests the two exposures may exert independent effects via different biological mechanism on wheeze.
prenatal exposure to polycyclic aromatic hydrocarbons; biomarkers of exposure; DNA adducts; early wheeze; 4-year olds; 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 years 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 literature 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.
cognitive development; children; wheezing phenotypes; birth cohort study
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.
gene–environment interactions; growth curves; Wald test; parametric bootstrap
We previously reported an association between prenatal exposure to airborne PAH and lower birth weight, birth length and head circumference. The main goal of the present analysis was to assess the possible impact of co-exposure to PAH-containing of barbecued meat consumed during pregnancy on birth outcomes.
The birth cohort consisted of 432 pregnant women who gave birth at term (>36 weeks of gestation). Only non-smoking women with singleton pregnancies, 18-35 years 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 (birthweight, length and head circumference at birth) was adjusted in multiple linear regression models for potential confounding factors such as prenatal exposure to airborne PAHs, child’s sex, gestational age, parity, size of mother (maternal prepregnancy weight, weight gain in pregnancy) and prenatal environmental tobacco smoke (ETS).
The multivariable regression model showed a significant deficit in birthweight 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 birthweight could not have been mediated by shortened gestation period.
In conclusion, the study results provided epidemiologic evidence that prenatal PAH exposure from diet including grilled meat might be hazardous for fetal development.
barbecued meat; pregnancy; birth weight; birth cohort study
Prenatal Paracetamol (Acetaminophen) has been associated with increased risk of allergic disease in early childhood, an association that could be due to increased altered susceptibility induced by air pollutants. The main goal of the study was to test the hypothesis that prenatal Paracetamol exposure increases the risk of developing eczema in early childhood and that this association is stronger for children who are exposed prenatally to higher concentrations of fine particulate matter (PM2.5). The study sample consisted of 322 women recruited from January 2001 to February 2004 in the Krakow inner city area who gave birth to term babies and completed 5-year follow-up. Paracetamol use in pregnancy was collected by interviews and prenatal personal exposure to over 48 hours was measured in all recruited women in the second trimester of PM2.5 pregnancy. After delivery, every three months in the first 24 months of the newborn’s life and every 6 months later, a detailed standardized face-to-face interview on the infant’s health was administered to each mother by a trained interviewer. During the interviews at each of the study periods after birth, a history of eczema was recorded.
By Cox proportional hazard regression, prenatal exposure to Paracetamol increased the risk of eczema by 20% and PM2.5 by 6%, albeit non significantly. However, the the joint exposure to Paracetamol and higher prenatal PM2.5 was significant and doubled the risk of eczema symptoms (HR = 2.07, 95%CI: 1.01 – 4.34). The findings suggest that even very small doses of Paracetamol in pregnancy may affect the occurrence of allergy outcomes such as eczema in early childhood but only at the co-exposure to higher fine particulate matter.
birth cohort study; eczema; children; acetaminophen; pregnancy; prenatal fine particulate matter
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.
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.
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).
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.
Fish consumption; Prenatal exposure to fine particles; Cow's milk allergy; Passive tobacco smoke; Cohort study
Exposure to fine particulate matter (PM) is a recognized risk factor for elevated blood pressure (BP) and cardiovascular disease in adults, and this prospective cohort study was undertaken to evaluate whether gestational exposure to PM2.5 has a prohypertensive effect. We measured personal exposure to fine particulate matter (PM2.5) by personal air monitoring in the second trimester of pregnancy among 431 women, and BP values in the third trimester were obtained from medical records of prenatal care clinics. In the general estimating equation model, the effect of PM2.5 on BP was adjusted for relevant covariates such as maternal age, education, parity, gestational weight gain (GWG), prepregnancy BMI, environmental tobacco smoke (ETS), and blood lead level. Systolic blood pressure (SBP) increased in a linear fashion across a dosage of PM2.5 and on average augmented by 6.1 mm Hg (95% CI, 0.6–11.6) with log unit of PM2.5 concentration. Effects of age, maternal education, prepregnancy BMI, blood lead level, and ETS were insignificant. Women with excessive gestational weight gain (>18 kg) had higher mean SBP parameters by 5.5 mmHg (95% CI, 2.7–8.3). In contrast, multiparous women had significantly lower SBP values (coeff. = −4.2 mm Hg; 95% CI, −6.8 to −1.6). Similar analysis performed for diastolic blood pressure (DBP) has demonstrated that PM2.5 also affected DBP parameters (coeff. = 4.1; 95% CI, −0.02 to 8.2), but at the border significance level. DBP values were positively associated with the excessive GWG (coeff. = 2.3; 95% CI, 0.3–4.4) but were inversely related to parity (coeff. = −2.7; 95% CI, −4.6 to −0.73). In the observed cohort, the exposure to fine particulate matter during pregnancy was associated with increased maternal blood pressure.
Blood pressure; Exposure to fine particulate matter; Pregnancy; Gestational weight gain; Prepregnancy ponderal index; Environmental tobacco smoke
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.
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.
birth cohort study; lead; intrauterine exposure; atopy; children
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.
The purpose of the study was to assess the neurocognitive status of 6-month-old infants whose mothers were exposed to low but varying amounts of lead during pregnancy. Lead levels in the cord blood were used to assess environmental exposure and the Fagan Test of Infant Intelligence (FTII) assessed visual recognition memory (VRM). The cohort consisted of 452 infants of mothers who gave birth to babies at 33–42 weeks of gestation between January 2001 and March 2003. The overall mean lead level in the cord blood was 1.42 μg/dl (95% CI: 1.35–1.48). We found that VRM scores in 6 month olds were inversely related to lead cord blood levels (Spearman correlation coefficient −0.16, p = 0.007). The infants scored lower by 1.5 points with an increase by one unit (1 μg/dl) of lead concentration in cord blood. In the lower exposed infants (≤1.67 μg/dl) the mean Fagan score was 61.0 (95% CI: 60.3–61.7) and that in the higher exposed group (>1.67 μg/dl) was 58.4 (95% CI: 57.3–59.7). The difference of 2.5 points was significant at the p = 0.0005 level. The estimated risk of scoring the high-risk group of developmental delay (FTII classification 3) due to higher lead blood levels was two-fold greater (OR = 2.33, 95% CI: 1.32–4.11) than for lower lead blood levels after adjusting for potential confounders (gestational age, gender of the child and maternal education). As the risk of the deficit in VRM score (Fagan group 3) in exposed infants attributable to Pb prenatal exposure was about 50%, a large portion of cases with developmental delay could be prevented by reducing maternal blood lead level below 1.67 μg/dl. Although the negative predictive value of the chosen screening criterion (above 1.67 μg/dl) was relatively high (89%) its positive predictive value was too low (22%), so that the screening program based on the chosen cord blood lead criterion was recommended.
Prenatal lead exposure; Biological markers; Infant visual recognition memory; Neurocognitive development
The fetus is more susceptible than the adult to the effects of certain carcinogens, such as polycyclic aromatic hydrocarbons (PAH). Nutritional factors, including antioxidants, have been shown to have a protective effect on carcinogen-DNA adducts and cancer risk in adults. We investigated whether the effect of prenatal airborne PAH exposure, measured by personal air monitoring during pregnancy, on the level of PAH-DNA adducts in a baby's cord blood is modified by the concentration of micronutrients in maternal and cord blood. The micronutrients examined were: retinol (vitamin A), α-tocopherol and γ-tocopherol (vitamin E), and carotenoids. With the use of multiple linear regression, we found a significant interaction between prenatal PAH exposure and cord blood concentration of α-tocopherol and carotenoids in predicting the concentration of PAH adducts in cord blood. The association between PAH exposure and PAH adducts was much stronger among those with low α-tocopherol (β = 0.15; P = 0.001) and among those with low carotenoids (β = 0.16; P < 0.001) compared with babies with high levels of these micronutrients (among those with high α-tocopherol: β = 0.05; P = 0.165; among those with high carotenoids: β = 0.06; P = 0.111). These results suggest a protective effect of micronutrients on the DNA damage and potential cancer risk associated with prenatal PAH exposure.
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.
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 μm in size (PM2.5) were carried out by personal air monitoring over 48 h during the second trimester of pregnancy. The effect of PM2.5 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.
The study showed that the adjusted birth weight was significantly lower in newborns whose mothers were exposed to particulate matter greater than 46.3 μg/m3 (β 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 PM2.5 and fish intake levels was also insignificant (β = −107,35, p = 0.215). Neither gestational age nor birth weight correlated with maternal fish consumption.
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.
Air pollutants; Prenatal exposure; Fish consumption; Birth size; Cohort study
Prenatal exposures such as polycyclic aromatic hydrocarbons (PAH) 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 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.
gene-environment interaction; mother-child pair design; likelihood ratio test
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 or detoxification genes affect child cognitive development following PAH exposure during pregnancy. In two parallel prospective cohort studies of nonsmoking 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), as measured by the Bayley Scales of Infant Development-Revised (BSID-II). 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: African Americans, Dominicans, and Caucasians. PAHs were measured by personal air monitoring of mothers during pregnancy. Significant interaction effects between haplotypes and PAHs were observed in mothers and their newborns in all three ethnic groups after Bonferroni correction for multiple comparisons. The strongest and most consistent effect observed was between PAH and haplotype ACCGGC of the CYP1B1 gene.
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.
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.
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).
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.
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.
air pollution; child; development; environmental; ETS; in utero; intelligence; prenatal; Poland; Raven
The main goal of the paper was to assess the pattern of risk factors having an impact on the onset of early wheezing phenotypes in the birth cohort of 468 two-year olds and to investigate the severity of respiratory illness in the two-year olds in relation to both wheezing phenotypes, environmental tobacco smoke (ETS) and personal PM2.5 exposure over pregnancy period (fine particulate matter). The secondary goal of the paper was to assess possible association of early persistent wheezing with the length of the baby at birth. Pregnant women were recruited from ambulatory prenatal clinics in the first and second trimester of pregnancy. 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. In the statistical analysis of respiratory health of children multinomial logistic regression and zero-inflated Poisson regression models were used. Approximately one third of the children in the study sample experienced wheezing in the first two years of life and in about two third of cases (67%) the symptom developed already in the first year of life. The early wheezing was easily reversible and in about 70% of infants with wheezing the symptom receded in the second year of life. The adjusted relative risk ratio (RRR) of persistent wheezing increased with maternal atopy (RRR = 3.05; 95%CI: 1.30 – 7.15), older siblings (RRR = 3.05; 95%CI: 1.67 – 5.58) and prenatal ETS exposure (RRR= 1.13; 95%CI: 1.04 – 1.23), but was inversely associated with the length of baby at birth (RRR = 0.88; 95%CI: 0.76 – 1.01). The adjusted incidence risk ratios (IRR) of coughing, difficult breathing, runny/stuffy nose and pharyngitis/tonsillitis in wheezers were much higher than that observed among non-wheezers and significantly depended on prenatal PM2.5 exposure, older siblings and maternal atopy. The study shows a clear inverse association between maternal age or maternal education and respiratory illnesses and calls for more research efforts aiming at explanation of factors hidden behind proxy measures of quality of maternal care of babies. The data support the hypothesis that burden of respiratory symptoms in early childhood and possibly in later life may be programmed already in prenatal period when the respiratory system is completing its growth and maturation.
wheezing phenotypes; respiratory symptoms; prenatal and postnatal environmental air quality; birth cohort study
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.
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.
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.
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.
Copyright © 2009 S. Karger AG, Basel
Prenatal lead exposure; Infant cognitive functioning; Infant psychomotor functioning; Prospective cohort study