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1.  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.
doi:10.1159/000320376
PMCID: PMC3047761  PMID: 21293147
Fish consumption; Prenatal exposure to fine particles; Cow's milk allergy; Passive tobacco smoke; Cohort study
2.  Gender differences in fetal growth of newborns exposed prenatally to airborne fine particulate matter 
Environmental research  2009;109(4):447-456.
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.
doi:10.1016/j.envres.2009.01.009
PMCID: PMC3786262  PMID: 19261271
Cohort study; Prenatal exposure; Air pollutants; Fine particles; Gender; Fetal growth deficits
3.  Estimated Risk for Altered Fetal Growth Resulting from Exposure to Fine Particles during Pregnancy: An Epidemiologic Prospective Cohort Study in Poland 
Environmental Health Perspectives  2004;112(14):1398-1402.
The purpose of this study was to estimate exposure of pregnant women in Poland to fine particulate matter [≤2.5 μm in diameter (PM2.5)] and to assess its effect on the birth outcomes. The cohort consisted of 362 pregnant women who gave birth between 34 and 43 weeks of gestation. The enrollment included only nonsmoking women with singleton pregnancies, 18–35 years of age, who were free from chronic diseases such as diabetes and hypertension. PM2.5 was measured by personal air monitoring over 48 hr during the second trimester of pregnancy. All assessed birth effects were adjusted in multiple linear regression models for potential confounding factors such as the size of mother (maternal height, prepregnancy weight), parity, sex of child, gestational age, season of birth, and self-reported environmental tobacco smoke (ETS). The regression model explained 35% of the variability in birth weight (β = −200.8, p = 0.03), and both regression coefficients for PM2.5 and birth length (β = −1.44, p = 0.01) and head circumference (HC; β = −0.73, p = 0.02) were significant as well. In all regression models, the effect of ETS was insignificant. Predicted reduction in birth weight at an increase of exposure from 10 to 50 μg/m3 was 140.3 g. The corresponding predicted reduction of birth length would be 1.0 cm, and of HC, 0.5 cm. The study provides new and convincing epidemiologic evidence that high personal exposure to fine particles is associated with adverse effects on the developing fetus. These results indicate the need to reduce ambient fine particulate concentrations. However, further research should establish possible biologic mechanisms explaining the observed relationship.
doi:10.1289/ehp.7065
PMCID: PMC1247567  PMID: 15471732
air pollutants; cohort study; fetal growth; pregnancy; prenatal exposure
4.  JOINT EFFECT OF PRENATAL EXPOSURE TO FINE PARTICULATE MATTER AND INTAKE OF PARACETAMOL (ACETAMINOPHEN) IN PREGNANCY ON ONSET OF ECZEMA IN EARLY CHILDHOOD. PROSPECTIVE BIRTH COHORT STUDY 
The Science of the total environment  2011;409(24):5205-5209.
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.
doi:10.1016/j.scitotenv.2011.08.068
PMCID: PMC3428593  PMID: 21962593
birth cohort study; eczema; children; acetaminophen; pregnancy; prenatal fine particulate matter
5.  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 
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.
doi:10.1016/j.nut.2011.07.020
PMCID: PMC3288524  PMID: 22079395
barbecued meat; pregnancy; birth weight; birth cohort study
6.  EARLY WHEEZING PHENOTYPES AND SEVERITY OF RESPIRATORY ILLNESS IN VERY EARLY CHILDHOOD. STUDY ON INTRAUTERINE EXPOSURE TO FINE PARTICLE MATTER 
Environment international  2009;35(6):877-884.
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.
doi:10.1016/j.envint.2009.03.004
PMCID: PMC2709737  PMID: 19394697
wheezing phenotypes; respiratory symptoms; prenatal and postnatal environmental air quality; birth cohort study
7.  Prohypertensive Effect of Gestational Personal Exposure to Fine Particulate Matter. Prospective Cohort Study in Non-smoking and Non-obese Pregnant Women 
Cardiovascular Toxicology  2012;12(3):216-225.
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.
doi:10.1007/s12012-012-9157-z
PMCID: PMC3404286  PMID: 22328329
Blood pressure; Exposure to fine particulate matter; Pregnancy; Gestational weight gain; Prepregnancy ponderal index; Environmental tobacco smoke
8.  Maternal exposure to air pollution before and during pregnancy related to changes in newborn's cord blood lymphocyte subpopulations. The EDEN study cohort 
Background
Toxicants can cross the placenta and expose the developing fetus to chemical contamination leading to possible adverse health effects, by potentially inducing alterations in immune competence. Our aim was to investigate the impacts of maternal exposure to air pollution before and during pregnancy on newborn's immune system.
Methods
Exposure to background particulate matter less than 10 μm in diameter (PM10) and nitrogen dioxide (NO2) was assessed in 370 women three months before and during pregnancy using monitoring stations. Personal exposure to four volatile organic compounds (VOCs) was measured in a subsample of 56 non-smoking women with a diffusive air sampler during the second trimester of pregnancy. Cord blood was analyzed at birth by multi-parameter flow cytometry to determine lymphocyte subsets.
Results
Among other immunophenotypic changes in cord blood, decreases in the CD4+CD25+ T-cell percentage of 0.82% (p = 0.01), 0.71% (p = 0.04), 0.88% (p = 0.02), and 0.59% (p = 0.04) for a 10 μg/m3 increase in PM10 levels three months before and during the first, second and third trimester of pregnancy, respectively, were observed after adjusting for confounders. A similar decrease in CD4+CD25+ T-cell percentage was observed in association with personal exposure to benzene. A similar trend was observed between NO2 exposure and CD4+CD25+ T-cell percentage; however the association was stronger between NO2 exposure and an increased percentage of CD8+ T-cells.
Conclusions
These data suggest that maternal exposure to air pollution before and during pregnancy may alter the immune competence in offspring thus increasing the child's risk of developing health conditions later in life, including asthma and allergies.
doi:10.1186/1471-2393-11-87
PMCID: PMC3227583  PMID: 22047167
9.  Impact of ambient air pollution on birth weight in Sydney, Australia 
Background: Studies in Asia, Europe, and the Americas have provided evidence that ambient air pollution may have an adverse effect on birth weight, although results are not consistent.
Methods: Average exposure during pregnancy to five common air pollutants was estimated for births in metropolitan Sydney between 1998 and 2000. The effects of pollutant exposure in the first, second, and third trimesters of pregnancy on risk of "small for gestational age" (SGA), and of pollutant exposure during pregnancy on birth weight were examined.
Results: There were 138 056 singleton births in Sydney between 1998 and 2000; 9.7% of babies (13 402) were classified as SGA. Air pollution levels in Sydney were found to be quite low. In linear regression models carbon monoxide and nitrogen dioxide concentrations in the second and third trimesters had a statistically significant adverse effect on birth weight. For a 1 part per million increase in mean carbon monoxide levels a reduction of 7 (95% CI –5 to 19) to 29 (95% CI 7 to 51) grams in birth weight was estimated. For a 1 part per billion increase in mean nitrogen dioxide levels a reduction of 1 (95% CI 0 to 2) to 34 (95% CI 24 to 43) grams in birth weight was estimated. Particulate matter (diameter less than ten microns) in the second trimester had a small statistically significant adverse effect on birth weight. For a 1 microgram per cubic metre increase in mean particulate matter levels a reduction of 4 grams (95% CI 3 to 6) in birth weight was estimated.
Conclusion: These findings of an association between carbon monoxide, nitrogen dioxide, and particulate matter, and reduction in birth weight should be corroborated by further study.
doi:10.1136/oem.2004.014282
PMCID: PMC1741072  PMID: 16046604
10.  Air pollution exposure during pregnancy and reduced birth size: a prospective birth cohort study in Valencia, Spain 
Background
Maternal exposure to air pollution has been related to fetal growth in a number of recent scientific studies. The objective of this study was to assess the association between exposure to air pollution during pregnancy and anthropometric measures at birth in a cohort in Valencia, Spain.
Methods
Seven hundred and eighty-five pregnant women and their singleton newborns participated in the study. Exposure to ambient nitrogen dioxide (NO2) was estimated by means of land use regression. NO2 spatial estimations were adjusted to correspond to relevant pregnancy periods (whole pregnancy and trimesters) for each woman. Outcome variables were birth weight, length, and head circumference (HC), along with being small for gestational age (SGA). The association between exposure to residential outdoor NO2 and outcomes was assessed controlling for potential confounders and examining the shape of the relationship using generalized additive models (GAM).
Results
For continuous anthropometric measures, GAM indicated a change in slope at NO2 concentrations of around 40 μg/m3. NO2 exposure >40 μg/m3 during the first trimester was associated with a change in birth length of -0.27 cm (95% CI: -0.51 to -0.03) and with a change in birth weight of -40.3 grams (-96.3 to 15.6); the same exposure throughout the whole pregnancy was associated with a change in birth HC of -0.17 cm (-0.34 to -0.003). The shape of the relation was seen to be roughly linear for the risk of being SGA. A 10 μg/m3 increase in NO2 during the second trimester was associated with being SGA-weight, odds ratio (OR): 1.37 (1.01-1.85). For SGA-length the estimate for the same comparison was OR: 1.42 (0.89-2.25).
Conclusions
Prenatal exposure to traffic-related air pollution may reduce fetal growth. Findings from this study provide further evidence of the need for developing strategies to reduce air pollution in order to prevent risks to fetal health and development.
doi:10.1186/1476-069X-9-6
PMCID: PMC2845572  PMID: 20113501
11.  EFFECT OF PRENATAL EXPOSURE TO FINE PARTICULATE MATTER ON VENTILATORY LUNG FUNCTION OF PRESCHOOL CHILDREN OF NONSMOKING MOTHERS. KRAKOW INNER CITY BIRTH COHORT PROSPECTIVE STUDY 
SUMMARY
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.
doi:10.1111/j.1365-3016.2010.01136.x
PMCID: PMC3761386  PMID: 20670230
prenatal exposure; air pollution; birth cohort; lung function; preschool children
12.  Impact of ambient air pollution on gestational age is modified by season in Sydney, Australia 
Environmental Health  2007;6:16.
Background
The effect of individual pollutants and the period(s) during pregnancy when pollutant levels are likely to have most impact on preterm birth is not clear. We evaluated the effect of prenatal exposure to six common urban air pollutants in the Sydney metropolitan area on preterm birth.
Methods
We obtained information on all births in metropolitan Sydney between January 1, 1998 and December 31, 2000. For each birth, exposure to each air pollutant was estimated for the first trimester, the three months preceding birth, the first month after the estimated date of conception and the month prior to delivery. Gestational age was analysed as a categorical variable in logistic regression models.
Results
There were 123 840 singleton births in Sydney in 1998–2000 and 4.9% were preterm. Preterm birth was significantly associated with maternal age, maternal smoking, male infant, indigenous status and first pregnancy. Air pollutant levels in the month and three months preceding birth had no significant effect on preterm birth after adjusting for maternal and infant covariates. Ozone levels in the first trimester of pregnancy and spring months of conception and sulphur dioxide were associated with increased risks for preterm births. Nitrogen dioxide was associated with a decreased risk of preterm births.
Conclusion
We found more protective than harmful associations between ambient air pollutants and preterm births with most associations non-significant. In view of these inconsistent associations, it is important to interpret the harmful effects with caution. If our results are confirmed by future studies then it will be imperative to reduce Sydney's already low air pollution levels even further.
doi:10.1186/1476-069X-6-16
PMCID: PMC1894960  PMID: 17553174
13.  Air Pollution Exposure During Pregnancy, Ultrasound Measures of Fetal Growth, and Adverse Birth Outcomes: A Prospective Cohort Study 
Environmental Health Perspectives  2011;120(1):150-156.
Background: Air pollution exposure during pregnancy might have trimester-specific effects on fetal growth.
Objective: We prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands.
Methods: Particulate matter with an aerodynamic diameter < 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records.
Results: In cross-sectional analyses, NO2 levels were inversely associated with fetal femur length in the second and third trimester, and PM10 and NO2 levels both were associated with smaller fetal head circumference in the third trimester [–0.18 mm, 95% confidence interval (CI): –0.24, –0.12 mm; and –0.12 mm, 95% CI: –0.17, –0.06 mm per 1-μg/m3 increase in PM10 and NO2, respectively]. Average PM10 and NO2 levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (–3.6 g, 95% CI: –6.7, –0.4 g; and –3.4 g, 95% CI: –6.2, –0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM10 exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM10 exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO2 levels and adverse birth outcomes.
Conclusions: Results suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with weight at birth. PM10 exposure was positively associated with preterm birth and SGA.
doi:10.1289/ehp.1003316
PMCID: PMC3261932  PMID: 22222601
air pollution; birth weight; dispersion modeling; fetal growth; intrauterine growth restriction; nitrogen dioxide; particulate matter; pregnancy; preterm birth
14.  Ambient air pollution exposure and full-term birth weight in California 
Environmental Health  2010;9:44.
Background
Studies have identified relationships between air pollution and birth weight, but have been inconsistent in identifying individual pollutants inversely associated with birth weight or elucidating susceptibility of the fetus by trimester of exposure. We examined effects of prenatal ambient pollution exposure on average birth weight and risk of low birth weight in full-term births.
Methods
We estimated average ambient air pollutant concentrations throughout pregnancy in the neighborhoods of women who delivered term singleton live births between 1996 and 2006 in California. We adjusted effect estimates of air pollutants on birth weight for infant characteristics, maternal characteristics, neighborhood socioeconomic factors, and year and season of birth.
Results
3,545,177 singleton births had monitoring for at least one air pollutant within a 10 km radius of the tract or ZIP Code of the mother's residence. In multivariate models, pollutants were associated with decreased birth weight; -5.4 grams (95% confidence interval -6.8 g, -4.1 g) per ppm carbon monoxide, -9.0 g (-9.6 g, -8.4 g) per pphm nitrogen dioxide, -5.7 g (-6.6 g, -4.9 g) per pphm ozone, -7.7 g (-7.9 g, -6.6 g) per 10 μg/m3 particulate matter under 10 μm, -12.8 g (-14.3 g, -11.3 g) per 10 μg/m3 particulate matter under 2.5 μm, and -9.3 g (-10.7 g, -7.9 g) per 10 μg/m3 of coarse particulate matter. With the exception of carbon monoxide, estimates were largely unchanged after controlling for co-pollutants. Effect estimates for the third trimester largely reflect the results seen from full pregnancy exposure estimates; greater variation in results is seen in effect estimates specific to the first and second trimesters.
Conclusions
This study indicates that maternal exposure to ambient air pollution results in modestly lower infant birth weight. A small decline in birth weight is unlikely to have clinical relevance for individual infants, and there is debate about whether a small shift in the population distribution of birth weight has broader health implications. However, the ubiquity of air pollution exposures, the responsiveness of pollutant levels to regulation, and the fact that the highest pollution levels in California are lower than those regularly experienced in other countries suggest that precautionary efforts to reduce pollutants may be beneficial for infant health from a population perspective.
doi:10.1186/1476-069X-9-44
PMCID: PMC2919523  PMID: 20667084
15.  The effect of ambient carbon monoxide on low birth weight among children born in southern California between 1989 and 1993. 
We evaluated the effect of carbon monoxide (CO) exposures during the last trimester of pregnancy on the frequency of low birth weight among neonates born 1989-1993 to women living in the Los Angeles, California, area. Using birth certificate data for that period, we assembled a retrospective cohort of infants whose mothers resided within 2 miles of 1 of 18 CO monitoring stations. Based on the gestational age and birth date of each child, we estimated last-trimester exposure by averaging the corresponding 3 months of daily CO concentrations registered at the monitoring station closest to the mother's residence (determined from the birth certificate). Where data were available (at 6 stations), we also averaged measurements taken daily for nitrogen dioxide and ozone and those taken at 6-day intervals for particulate matter [less than/equal to]10 microm (PM10) to approximate last-trimester exposures to other pollutants. Overall, the study cohort consisted of 125,573 singleton children, excluding infants born before 37 or after 44 weeks of gestation, those weighing below 1,000 or above 5,500 g at birth, those for whom fewer than 10 days of CO measurements were available during the last trimester, and those whose mothers suffered from hypertension, diabetes, or uterine bleeding during pregnancy. Within the cohort, 2,813 (2.2%) were low in birth weight (between 1,000 and 2,499 g). Exposure to higher levels of ambient CO (>5.5 ppm 3-month average) during the last trimester was associated with a significantly increased risk for low birth weight [odds ratio (OR) = 1.22; 95% confidence interval (CI), 1.03-1.44] after adjustment for potential confounders, including commuting habits in the monitoring area, sex of the child, level of prenatal care, and age, ethnicity, and education of the mother.
PMCID: PMC1566307  PMID: 9872713
16.  Ambient Air Pollution and Low Birth Weight in Connecticut and Massachusetts 
Environmental Health Perspectives  2007;115(7):1118-1124.
Background
Several studies have examined whether air pollution affects birth weight; however results vary and many studies were focused on Southern California or were conducted outside of the United States.
Objectives
We investigated maternal exposure to particulate matter with aerodynamic diameter < 10, < 2.5 μm (PM10, PM2.5), sulfur dioxide, nitrogen dioxide, and carbon monoxide and birth weight for 358,504 births in Massachusetts and Connecticut from 1999 to 2002.
Methods
Analysis included logistic models for low birth weight (< 2,500 g) and linear models with birth weight as a continuous variable. Exposure was assigned as the average county-level concentration over gestation and each trimester based on mother’s residence. We adjusted for gestational length, prenatal care, type of delivery, child’s sex, birth order, weather, year, and mother’s race, education, marital status, age, and tobacco use.
Results
An interquartile increase in gestational exposure to NO2, CO, PM10, and PM2.5 lowered birth weight by 8.9 g [95% confidence interval (CI), 7.0–10.8], 16.2 g (95% CI, 12.6–19.7), 8.2 g (95% CI, 5.3–11.1), and 14.7 g (95% CI, 12.3–17.1), respectively. Lower birth weight was associated with exposure in the third trimester for PM10, the first and third trimesters for CO, the first trimester for NO2 and SO2, and the second and third trimesters for PM2.5. Effect estimates for PM2.5 were higher for infants of black mothers than those of white mothers.
Conclusions
Results indicate that exposure to air pollution, even at low levels, may increase risk of low birth weight, particularly for some segments of the population.
doi:10.1289/ehp.9759
PMCID: PMC1913584  PMID: 17637932
Air pollution; birth weight; carbon monoxide; nitrogen dioxide; particulate matter; PM10; PM2.5; pregnancy; sulfur dioxide
17.  Prenatal Exposure to Wood Fuel Smoke and Low Birth Weight 
Environmental Health Perspectives  2008;116(4):543-549.
Background
Maternal exposure to wood fuel smoke may lead to impaired fetal growth due to hypoxia and or oxidative stress from smoke constituents such as carbon monoxide and particulate matter.
Objectives
We studied the risk of low birth weight (LBW) and reduced mean birth weight in relation to reported use of wood for cooking during the prenatal period, compared with natural gas (NG).
Methods
We studied a historical cohort of women who had a singleton live birth in the years 2000–2002, from a semirural area of Pakistan. Infant’s birth weight was obtained from records, and prenatal records had data for maternal body mass index and parity. Cooking habits, daytime sleep habits, and type of fuel used during the pregnancies in 2000–2002 were ascertained by a survey done in 2004–2005. We performed multiple linear and logistic regression modeling using propensity scores to adjust for confounding variables.
Results
Unadjusted mean (± SD) birth weight was 2.78 ± 0.45 kg in wood users, and 2.84 ± 0.43 kg (p < 0.06) in NG users. Infants born to wood users averaged 82 g lighter than infants born to NG users when weight was adjusted for confounders (p < 0.07). The rate of LBW (< 2,500 g) was 22.7% among wood users compared with 15.0% in NG users (p < 0.01), for an adjusted relative risk of 1.64 (95% confidence interval, 1.10–2.34). The population attributable risk for LBW explained by wood use was estimated to be 24%.
Conclusion
Cooking with wood fuel during pregnancy, a potentially modifiable exposure, was associated with LBW and marginally lower mean birth weight compared with using NG.
doi:10.1289/ehp.10782
PMCID: PMC2290983  PMID: 18414641
birth weight; cooking habits; historical cohort; natural gas; pregnancy; propensity scores
18.  Residential Exposure to Outdoor Air Pollution during Pregnancy and Anthropometric Measures at Birth in a Multicenter Cohort in Spain 
Environmental Health Perspectives  2011;119(9):1333-1338.
Background: A growing body of research suggests that prenatal exposure to air pollution may be harmful to fetal development. We assessed the association between exposure to air pollution during pregnancy and anthropometric measures at birth in four areas within the Spanish Children’s Health and Environment (INMA) mother and child cohort study.
Methods: Exposure to ambient nitrogen dioxide (NO2) and benzene was estimated for the residence of each woman (n = 2,337) for each trimester and for the entire pregnancy. Outcomes included birth weight, length, and head circumference. The association between residential outdoor air pollution exposure and birth outcomes was assessed with linear regression models controlled for potential confounders. We also performed sensitivity analyses for the subset of women who spent more time at home during pregnancy. Finally, we performed a combined analysis with meta-analysis techniques.
Results: In the combined analysis, an increase of 10 µg/m3 in NO2 exposure during pregnancy was associated with a decrease in birth length of –0.9 mm [95% confidence interval (CI), –1.8 to –0.1 mm]. For the subset of women who spent ≥ 15 hr/day at home, the association was stronger (–0.16 mm; 95% CI, –0.27 to –0.04). For this same subset of women, a reduction of 22 g in birth weight was associated with each 10-µg/m3 increase in NO2 exposure in the second trimester (95% CI, –45.3 to 1.9). We observed no significant relationship between benzene levels and birth outcomes.
Conclusions: NO2 exposure was associated with reductions in both length and weight at birth. This association was clearer for the subset of women who spent more time at home.
doi:10.1289/ehp.1002918
PMCID: PMC3230392  PMID: 21429861
air pollution; anthropometry; benzene; birth; birth weight; nitrogen dioxide; pregnancy
19.  Assessing Exposure Metrics for PM and Birthweight Models 
The link between air pollution exposure and adverse birth outcomes is of public health concern due to the relationship between poor pregnancy outcomes and the onset of childhood and adult diseases. As personal exposure measurements are difficult and expensive to obtain, proximate measures of air pollution exposure are traditionally used. We explored how different air pollution exposure metrics affect birthweight regression models. We examined the effect of maternal exposure to ambient levels of particulate matter <10, <2.5 μm in aerodynamic diameter (PM10, PM2.5) on birthweight among infants in North Carolina. We linked maternal residence to the closest monitor during pregnancy for 2000–2002 (n=350,754). County-level averages of air pollution concentrations were estimated for the entire pregnancy and each trimester. For a finer spatially resolved metric, we calculated exposure averages for women living within 20, 10, and 5 km of a monitor. Multiple linear regression was used to determine the association between exposure and birthweight, adjusting for standard covariates. In the county level model, an interquartile increase in PM10 and PM2.5 during the entire gestational period reduced birthweight by 5.3 g (95% CI: 3.3 – 7.4) and 4.6 g (95% CI: 2.3 – 6.8), respectively. This model also showed a reduction in birthweight for PM10 (7.1 g, 95% CI: 1.0–13.2) and PM2.5 (10.4 g, 95% CI: 6.4 – 14.4) during the third trimester. Proximity models for 20, 10, and 5 km distances showed similar results to the county level models. County level models assume that exposure is spatially homogeneous over a larger surface area than proximity models. Sensitivity analysis demonstrated that at varying spatial resolutions, there is still a stable and negative association between air pollution and birthweight, despite North Carolina’s consistent attainment of federal air quality standards.
doi:10.1038/jes.2009.52
PMCID: PMC2889210  PMID: 19773814
air pollution; particulate matter; birthweight; birth outcomes; exposure metrics
20.  Ambient Air Pollution and Preeclampsia: A Spatiotemporal Analysis 
Environmental Health Perspectives  2013;121(11-12):1365-1371.
Background: Available evidence concerning the association between air pollution and preeclampsia is limited, and specific associations with early- and late-onset preeclampsia have not been assessed.
Objectives: We investigated the association, if any, between preeclampsia (all, early-, and late-onset) and exposure to nitrogen dioxide, nitrogen oxides, particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5; fine particles), ≤ 10 μm, and 2.5–10 μm, and PM2.5 light absorption (a proxy for elemental carbon) during the entire pregnancy and during the first, second, and third trimesters.
Methods: This study was based on 8,398 pregnancies (including 103 cases of preeclampsia) among women residing in Barcelona, Spain (2000–2005). We applied a spatiotemporal exposure assessment framework using land use regression models to predict ambient pollutant levels during each week of pregnancy at the geocoded residence address of each woman at the time of birth. Logistic and conditional logistic regression models were used to estimate unadjusted and adjusted associations.
Results: We found positive associations for most of our evaluated outcome–exposure pairs, with the strongest associations observed for preeclampsia and late-onset preeclampsia in relation to the third-trimester exposure to fine particulate pollutants, and for early-onset preeclampsia in relation to the first-trimester exposure to fine particulate pollutants. Among our investigated associations, those of first- and third-trimester exposures to PM2.5 and third-trimester exposure to PM2.5 absorbance and all preeclampsia, and third-trimester PM2.5 exposure and late-onset preeclampsia attained statistical significance.
Conclusion: We observed increased risk of preeclampsia associated with exposure to fine particulate air pollution. Our findings, in combination with previous evidence suggesting distinct pathogenic mechanisms for early- and late-onset preeclampsia, support additional research on this topic.
Citation: Dadvand P, Figueras F, Basagaña X, Beelen R, Martinez D, Cirach M, Schembari A, Hoek G, Brunekreef B, Nieuwenhuijsen MJ. 2013. Ambient air pollution and preeclampsia: a spatiotemporal analysis. Environ Health Perspect 121:1365–1371; http://dx.doi.org/10.1289/ehp.1206430
doi:10.1289/ehp.1206430
PMCID: PMC3855505  PMID: 24021707
21.  Association between air pollution and preterm birth among neonates born in Isfahan, Iran 
Background:
Although several studies have investigated the association between maternal exposure to air pollution and preterm birth, the results are inconsistent. The aim of this study was to further investigate the relation between maternal exposure to ambient air pollution during pregnancy and the risk of preterm birth and low birth weight (LBW) in an Iranian pregnant population.
Materials and Methods:
In this study, we identified 4758 consecutive singleton birth records from one large referral hospital (2010-2012) in Isfahan, Iran. We identified cases of preterm birth and LBW, which were combined with meteorological and air pollution monitoring data. We estimated the effect of air pollution exposure during the entire pregnancy, each trimester, and last month, and preterm birth (gestational age <37 weeks) and LBW (<2500 g) by Pollutant Standard Index (PSI) using logistic regression adjusted for gestational age, neonate gender, birth order, and mother's age.
Results:
The PSI for entire pregnancy was significantly associated with preterm birth [Odds Ratio (95% CI) = 1.26 (1.20, 1.33)]. There was no association between maternal exposure to ambient air pollution and each trimester and the last month of pregnancy, and preterm birth or LBW.
Conclusion:
Maternal exposure to ambient air pollution during the entire pregnancy was associated with preterm birth in Isfahani women.
PMCID: PMC3897072  PMID: 24497859
Air pollution; low birth weight; Pollutant Standard Index; pregnancy outcome; premature birth; preterm delivery
22.  Effect of trihalomethane exposure on fetal development 
Aims: To examine the effect of trimester specific and pregnancy average total trihalomethane (TTHM) exposure on infant birth weight, low birth weight, and intrauterine growth retardation in term births, as well as gestational age and preterm delivery in all births.
Methods: Cross sectional analysis of 56 513 singleton infants born to residents of Massachusetts during 1990. City specific aggregate data were used to estimate maternal exposure to TTHM concentration; individual maternal information was used to adjust for confounding.
Results: Increased pregnancy average and second trimester TTHM exposure were associated with small for gestational age and reductions in birth weight after adjusting for potential confounding variables. Compared to ≤60 µg/l, pregnancy average TTHM exposure over 80 µg/l was associated with a 32 g reduction in birth weight. There was a 23 g reduction in birth weight in infants born to mothers exposed to greater than 80 µg/l TTHM during the second trimester. For each 20 µg/l increase in TTHM, the estimated reduction in birth was 2.8 g for pregnancy average exposure and 2.6 g for second trimester exposure. An increased risk of small for gestational age births was found for pregnancy average (odds ratio (OR) 1.14; 95% CI 1.02 to 1.26) and second trimester (OR 1.13, 95% CI 1.03 to 1.24) TTHM levels greater than 80 µg/l. There was no evidence of an association between preterm delivery and increased TTHM levels, but there were slight increases in gestational duration associated with TTHM concentrations.
Conclusions: Maternal exposure to THMs may be associated with fetal growth retardation. Our findings are consistent with most previous work, although we generally found smaller effects of TTHMs on low birth weight and intrauterine growth retardation.
doi:10.1136/oem.60.3.173
PMCID: PMC1740495  PMID: 12598663
23.  A Cohort Study of Traffic-Related Air Pollution Impacts on Birth Outcomes 
Environmental Health Perspectives  2008;116(5):680-686.
Background
Evidence suggests that air pollution exposure adversely affects pregnancy outcomes. Few studies have examined individual-level intraurban exposure contrasts.
Objectives
We evaluated the impacts of air pollution on small for gestational age (SGA) birth weight, low full-term birth weight (LBW), and preterm birth using spatiotemporal exposure metrics.
Methods
With linked administrative data, we identified 70,249 singleton births (1999–2002) with complete covariate data (sex, ethnicity, parity, birth month and year, income, education) and maternal residential history in Vancouver, British Columbia, Canada. We estimated residential exposures by month of pregnancy using nearest and inverse-distance weighting (IDW) of study area monitors [carbon monoxide, nitrogen dioxide, nitric oxide, ozone, sulfur dioxide, and particulate matter < 2.5 (PM2.5) or < 10 (PM10) μm in aerodynamic diameter], temporally adjusted land use regression (LUR) models (NO, NO2, PM2.5, black carbon), and proximity to major roads. Using logistic regression, we estimated the risk of mean (entire pregnancy, first and last month of pregnancy, first and last 3 months) air pollution concentrations on SGA (< 10th percentile), term LBW (< 2,500 g), and preterm birth.
Results
Residence within 50 m of highways was associated with a 26% increase in SGA [95% confidence interval (CI), 1.07–1.49] and an 11% (95% CI, 1.01–1.23) increase in LBW. Exposure to all air pollutants except O3 was associated with SGA, with similar odds ratios (ORs) for LUR and monitoring estimates (e.g., LUR: OR = 1.02; 95% CI, 1.00–1.04; IDW: OR = 1.05; 95% CI, 1.03–1.08 per 10-μg/m3 increase in NO). For preterm births, associations were observed with PM2.5 for births < 37 weeks gestation (and for other pollutants at < 30 weeks). No consistent patterns suggested exposure windows of greater relevance.
Conclusion
Associations between traffic-related air pollution and birth outcomes were observed in a population-based cohort with relatively low ambient air pollution exposure.
doi:10.1289/ehp.10952
PMCID: PMC2367679  PMID: 18470315
air pollution; birth weight; carbon black; carbon monoxide; nitrogen dioxide; nitric oxide; particulate matter; pregnancy; pregnancy outcome; preterm birth; soot; sulfur dioxide; vehicle emissions
24.  Traffic-Related Air Toxics and Term Low Birth Weight in Los Angeles County, California 
Environmental Health Perspectives  2011;120(1):132-138.
Background: Numerous studies have linked criteria air pollutants with adverse birth outcomes, but there is less information on the importance of specific emission sources, such as traffic, and air toxics.
Objectives: We used three exposure data sources to examine odds of term low birth weight (LBW) in Los Angeles, California, women when exposed to high levels of traffic-related air pollutants during pregnancy.
Methods: We identified term births during 1 June 2004 to 30 March 2006 to women residing within 5 miles of a South Coast Air Quality Management District (SCAQMD) Multiple Air Toxics Exposure Study (MATES III) monitoring station. Pregnancy period average exposures were estimated for air toxics, including polycyclic aromatic hydrocarbons (PAHs), source-specific particulate matter < 2.5 μm in aerodynamic diameter (PM2.5) based on a chemical mass balance model, criteria air pollutants from government monitoring data, and land use regression (LUR) model estimates of nitric oxide (NO), nitrogen dioxide (NO2) and nitrogen oxides (NOx). Associations between these metrics and odds of term LBW (< 2,500 g) were examined using logistic regression.
Results: Odds of term LBW increased approximately 5% per interquartile range increase in entire pregnancy exposures to several correlated traffic pollutants: LUR measures of NO, NO2, and NOx, elemental carbon, and PM2.5 from diesel and gasoline combustion and paved road dust (geological PM2.5).
Conclusions: These analyses provide additional evidence of the potential impact of traffic-related air pollution on fetal growth. Particles from traffic sources should be a focus of future studies.
doi:10.1289/ehp.1103408
PMCID: PMC3261935  PMID: 21835727
air pollution; air toxics; intrauterine growth retardation; low birth weight; traffic
25.  Oral Cleft Defects and Maternal Exposure to Ambient Air Pollutants in New Jersey 
Background
Evidence links exposure to ambient air pollution during pregnancy, particularly gaseous pollutants and particulate matter, to an increased risk of adverse reproductive outcomes but the results for birth defects have been inconsistent.
Methods
We compared estimated exposure to ambient air pollutants during early pregnancy among mothers of children with oral cleft defects (cases) to that among mothers of controls, adjusting for available risk factors from birth certificates. We obtained ambient air pollutant data from air monitoring sites in New Jersey for carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), sulfur dioxide (SO2), particulate matter less than 10 µm in aerodynamic diameter (PM10) and particulate matter less than 2.5 µm in aerodynamic diameter (PM2.5). We used values from the nearest monitor (within 40 km of the residence at birth) for controls, cleft lip with or without cleft palate (CLP) and cleft palate only (CPO).
Results
Based on logistic regression analyses for each contaminant and all contaminants together, there were no consistent elevated associations between selected air pollutants and cleft malformations. Quartile of CO concentration showed a consistent protective association with CPO (p<.01). For other contaminants, confidence intervals (95%) of the odds ratios for some quartiles excluded one. CLP showed limited evidence of an association with increasing SO2 exposure while CPO showed weak associations with increasing O3 exposure.
Conclusion
There was little consistent evidence associating cleft malformations with maternal exposure to ambient air pollutants. Evaluating particular pollutants or disease subgroups would require more detailed measurement of exposure and classification of cleft defects.
doi:10.1002/bdra.20650
PMCID: PMC2862481  PMID: 20146378

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