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International studies of prenatal exposure to polycyclic aromatic hydrocarbons and fetal growth.

OBJECTIVES: Polycyclic aromatic hydrocarbons polycyclic aromatic hydrocarbon
n.
Any of a class of carcinogenic organic molecules that consist of three or more rings containing carbon and hydrogen and that are commonly produced by fossil fuel combustion.
 (PAHs) are ubiquitously distributed human mutagens and carcinogens Mutagens and carcinogens

A mutagen is a substance or agent that induces heritable change in cells or organisms. A carcinogen is a substance that induces unregulated growth processes in cells or tissues of multicellular animals, leading to cancer.
. However, lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. To address this gap in knowledge, we examined the association between prenatal prenatal /pre·na·tal/ (-na´tal) preceding birth.

pre·na·tal
adj.
Preceding birth. Also called antenatal.



prenatal

preceding birth.
 exposure to airborne PAHs and birth weight, birth length, and birth head circumference, respectively, in Krakow, Poland, and New York City New York City: see New York, city.
New York City

City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S.
 (NYC NYC
abbr.
New York City


NYC New York City
).

METHODS: The parallel prospective cohort studies A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design.

In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute
 enrolled nonsmoking non·smok·ing  
adj.
1. Not engaging in the smoking of tobacco: nonsmoking passengers.

2. Designated or reserved for nonsmokers: the nonsmoking section of a restaurant.
, healthy, and nonoccupationally exposed women and their newborns. Personal air monitoring of pregnant women was conducted over 48 hr. To control for maternal environmental tobacco smoke environmental tobacco smoke (ETS/passive smoke),
n the gaseous by-product of burning tobacco products, including but not limited to commercially manufactured cigarettes and cigars; contains toxic elements harmful to the health of adults and children
 (ETS ETS Educational Testing Service (nonprofit private educational testing and measurement organization)
ETS Emergency Telecommunications Service
ETS Electronic Trading System
ETS Engineering (&) Technical Services
) exposure, we excluded those with umbilical cord umbilical cord (ŭmbĭl`ĭkəl), cordlike structure about 22 in. (56 cm) long in the pregnant human female, extending from the abdominal wall of the fetus to the placenta.  plasma cotinine cotinine (kō´tinēn),
n a substance that remains in body fluids after nicotine has been used. Presence of this chemical in body fluids is considered proof of recent nicotine use.
 concentrations > 25 ng/mL. Mean cord plasma cotinine concentrations in both ethnic groups were [less than or equal to] 0.5 ng/mL.

RESULTS: Prenatal PAH PAH, PAHA aminohippuric acid.

PAH
abbr.
para-aminohippuric acid


PAH 1 Polycyclic aromatic hydrocarbon, see there 2. Pulmonary artery HTN
 exposure was 10-fold higher in Krakow than in NYC. Prenatal PAH exposure was associated with significantly reduced birth weight in both Krakow Caucasians (p < 0.01) and in NYC African Americans African American Multiculture A person having origins in any of the black racial groups of Africa. See Race.  (p < 0.01), controlling for known and potential confounders, but not in NYC Dominicans. Within the lower exposure range common to the two cities (1.80-36.47 ng/[m.sup.3]), the effect per unit PAH exposure on birth weight was 6-fold greater for NYC African Americans than for Krakow Caucasians (p = 0.01).

CONCLUSIONS: These results confirm the adverse reproductive effect of relatively low PAH concentrations in two populations and suggest increased susceptibility susceptibility

the state of being susceptible. Refers usually to infectious disease but may be to physical factors such as wetting or to psychological factors such as harassment.
 of NYC African Americans. Fetal growth impairment Impairment

1. A reduction in a company's stated capital.

2. The total capital that is less than the par value of the company's capital stock.

Notes:
1. This is usually reduced because of poorly estimated losses or gains.

2.
 has been linked to child developmental and health problems. Thus, substantial health benefits would result from global reduction of PAH emissions.

KEY WORDS: birth outcomes, birth weight, fetal toxicity, personal air monitoring, polycyclic aromatic hydrocarbons, prenatal. Environ Health Perspect 114:1744-1750 (2006). doi:10.1289/ehp.8982 available via http://dx.doi.org/ [Online 3 August 2006]

**********

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants pollutants

see environmental pollution.
 generated by combustion sources that include diesel- and gasoline-powered motor vehicles, coal-fired power plants, residential heating, cooking, and tobacco smoking (Bostrom et al. 2002). An estimated > 80% of airborne PAHs results from the combustion of fossil fuels fossil fuel: see energy, sources of; fuel.
fossil fuel

Any of a class of materials of biologic origin occurring within the Earth's crust that can be used as a source of energy. Fossil fuels include coal, petroleum, and natural gas.
 and biomass (Bostrom et al. 2002). There is growing concern about the adverse effects of air pollution from fossil fuel combustion on public health (Bostrom et al. 2002; Brunekreef and Holgate 2002) and the global climate (National Academy of Sciences 2001). PAHs are human mutagens and carcinogens (Bostrom et al. 2002) and are potentially significant reproductive and developmental toxicants (Dejmek et al. 2000; Perera et al. 2003). For example, prenatal exposure of rats to 25-100 [micro]g/[m.sup.3] of the representative PAH, benzo[a]pyrene (BaP), through maternal inhalation inhalation /in·ha·la·tion/ (in?hah-la´shun)
1. the drawing of air or other substances into the lungs.inhala´tional

2. the drawing of an aerosolized drug into the lungs with the breath.

3.
 significantly decreased the fetal survival rate and birth weight in a dose-dependent manner (Archibong et al. 2002). In humans, associations between PAHs or PAH-DNA damage and fetal growth reduction have been reported in some but not all studies (Dejmek et al. 2000; Perera et al. 1998, 2003; Sram et al. 2005). In the Czech Republic Czech Republic, Czech Česká Republika (2005 est. pop. 10,241,000), republic, 29,677 sq mi (78,864 sq km), central Europe. It is bordered by Slovakia on the east, Austria on the south, Germany on the west, and Poland on the north. , ambient Surrounding. For example, ambient temperature and humidity are atmospheric conditions that exist at the moment. See ambient lighting.  PAHs significantly increased the risk of intrauterine growth retardation Intrauterine Growth Retardation Definition

Intrauterine growth retardation (IUGR) occurs when the unborn baby is at or below the 10th weight percentile for his or her age (in weeks).
 (IUGR IUGR intrauterine growth retardation (or restriction).

IUGR
abbr.
intrauterine growth retardation


IUGR Intrauterine growth retardation, see there
) both in Teplice and Prachatice (Dejmek et al. 2000). An earlier study in Poland found that the infants who had higher than median leukocyte leukocyte (l`kəsīt'): see blood.
leukocyte
 or white blood cell or white corpuscle
 PAH-DNA adduct adduct /ad·duct/ (ah-dukt´) to draw toward the median plane or (in the digits) toward the axial line of a limb.
adduct /ad·duct/ (a´dukt) inclusion complex.
 level had significantly reduced birth weight, length, and head circumference (Perera et al. 1998). In New Jersey, USA, the risk of fetal death, premature Death, Premature
See also Love, Tragic

Adonis

beautiful youth beloved by Venus, killed by a boar. [Gk. Myth.: Benét, 10]

L’Aiglon

Napoleon’s son dies before he can rouse the French to follow him. [Fr.
 birth, and low birth weight was significantly higher for those with a high prenatal polycyclic polycyclic

having two or more usually fused chemical ring structures in their molecule.


polycyclic hydrocarbons
thyroid initiators, i.e. they increase the incidence of thyroid tumors.
 organic matter exposure (Vassilev et al. 2001). However, the limitations of most prior studies [retrospective or cross-sectional design, reliance on ambient air monitoring data, failure to account for co-exposure to other sources of PAHs such as environmental tobacco smoke (ETS)] have prevented definitive causal inferences regarding airborne PAHs and impaired fetal growth (Sram et al. 2005).

We conducted two parallel prospective cohort studies in Krakow, Poland, and New York City (NYC), USA, using identical eligibility criteria, study design, and personal air monitoring methodology. Here we examined effects across the entire range of PAH exposure in each cohort separately, to understand the relationship between in utero in utero (in u´ter-o) [L.] within the uterus.

in u·ter·o
adj.
In the uterus.



in utero adv.
 exposure to airborne PAHs and fetal growth within each population. We also conducted exploratory analyses comparing the magnitude of PAH-related effects between the two different populations within the exposure range common to both, recognizing the limitations of such international, interethnic comparisons.

The U.S. and Polish cohorts represent a wide range of exposure, experienced in many other urban areas; therefore, study results in Krakow and NYC are relevant to other populations worldwide. In the Krakow cohort, the average PAH concentration estimated by personal air monitoring was 39.0 ng/[m.sup.3] (range, 1.8-272.2 ng/[m.sup.3]), compared with 3.3 ng/[m.sup.3] (range, 0.3-36.5 ng/[m.sup.3]) in NYC. Comparable personal air monitoring data on PAHs are not available for other populations, but stationary ambient air monitoring data for BaP can be used for comparison. The mean ambient BaP level in Krakow was 3.8 ng/[m.sup.3] in 2000. Annual mean ambient BaP level in various locations within Krakow ranged from 4 to 10 ng/[m.sup.3] during 2002. This level is comparable to the winter means reported in Teplice (7.42 ng/[m.sup.3]) and Prachatice (5.37 ng/[m.sup.3]), Czech Republic, between 1993 and 1994 (Binkova et al. 1999) but lower than that measured in Tongliang, China, between 2002 and 2003 (15 ng/[m.sup.3]) (Chow et al. 2006). In an ongoing prospective study in NYC, personal exposure to BaP among the cohort of pregnant women was 0.49 [+ or -] 0.65 ng/[m.sup.3] (Tonne et al. 2004). In U.S. cities, as well as in many urban areas of Europe, ambient BaP concentrations are generally < 1 ng/[m.sup.3], but may range between 1 and 5 ng/[m.sup.3] during winter or in areas with heavy traffic (Naumova et al. 2002; Tonne et al. 2004).

Methods

Subjects: Krakow study. Details on study design for the Krakow cohort have been previously published (Jedrychowski et al. 2004, 2006). Nonsmoking, pregnant women residing in the Srodmiescie (Old Podgorze) and the Krowodrza-Nowa Huta (New Podgorze) areas were recruited between November 2000 and March 2003 (Jedrychowski et al. 2004). Pregnant women were eligible if they were not currently smoking, registered at prenatal health care clinics in either of the two target areas, had lived at the present address for at least a year before the initial interview, were between the 8th and 24th weeks of gestation GESTATION, med. jur. The time during which a female, who has conceived, carries the embryo or foetus in her uterus. By the common consent of mankind, the term of gestation is considered to be ten lunar months, or forty weeks, equal to nine calendar months and a week. , were [greater than or equal to] 18 years of age, had no current occupational exposure to PAHs or other known developmental toxicants, had no history of illicit drug illicit drug Street drug, see there  use, pregnancy-related diabetes, or hypertension, and had a valid estimate of gestational age ges·ta·tion·al age
n.
See estimated gestational age.


Gestational age
The estimated age of a fetus expressed in weeks, calculated from the first day of the last normal menstrual period.
. Between the 20th and 30th week of pregnancy, research workers administered in-depth health, lifestyle, and environmental exposure (HLEE) questionnaires to women in their homes (Jedrychowski et al. 2004; Perera et al. 2003). On completing the interview, 48-hr personal air monitoring was carried out as described (Jedrychowski et al. 2004; Perera et al. 2003). To examine consistency in self-reporting, the interview was repeated during the third trimester Noun 1. third trimester - time period extending from the 28th week of gestation until delivery
trimester - a period of three months; especially one of the three three-month periods into which human pregnancy is divided
. After delivery, data on pregnancy and delivery were obtained from the mothers' and infants' medical records. Informed consent was obtained from all subjects and the study was approved by the ethics committee ethics committee A multidisciplinary hospital body composed of a broad spectrum of personnel–eg, physicians, nurses, social workers, priests, and others, which addresses the moral and ethical issues within the hospital. See DNR, Institutional review board.  of the Jagiellonian University
For several academies alternatively called "Krakow Academy", see Education in Kraków


The Jagiellonian University (Polish: Uniwersytet Jagielloński, often shortened to UJ
.

Subjects: NYC study. Details on study design and results on the initial 263 subjects for the NYC cohort have been previously published (Perera et al. 2003). The population residing in Washington Heights, Harlem, and the South Bronx is predominantly African American and Dominican. As previously described, women were recruited at the time of the first prenatal visit and were monitored during the third trimester (Perera et al. 2003). Ethnicity was self-identified. The same protocol as that for the Krakow cohort was used to conduct HLEE interviews, monitor personal exposure to PAHs, and collect birth outcome data. The present report includes 380 subjects as of September 2004, who met the inclusion criteria
For Wikipedia's inclusion criteria, see: What Wikipedia is not.


Inclusion criteria are a set of conditions that must be met in order to participate in a clinical trial.
 and had complete information on potential fetal growth confounders. The institutional review board of Columbia Presbyterian Medical Center approved the study, and informed consent was obtained from all study participants.

Air monitoring. Details of the personal air monitoring conducted in Krakow (Jedrychowski et al. 2004, 2006) and NYC (Perera et al. 2003; Tonne et al. 2004) have been published. Briefly, on completion of the interview, the women were given a backpack containing a portable personal exposure air monitor to be worn during the day and kept near the bed at night during a consecutive 48-hr period. Personal air monitoring data were given a quality assurance (QA) score (0-3) for flow rate, flow time, and completeness of documentation (Kinney et al. 2002). A final QA score of 0 (highest quality) or 1 (high quality) was required for inclusion. For both cohorts, the air extracts were analyzed at Southwest Research Institute Southwest Research Institute (SwRI), headquartered in San Antonio, Texas, is one of the oldest and largest independent, nonprofit, applied research and development (R&D) organizations in the United States. Founded in 1947 by Thomas Slick, Jr.  for levels of pyrene and eight carcinogenic carcinogenic

having a capacity for carcinogenesis.
 PAHs ([SIGMA]8 c-PAHs): benzo[a]anthracene anthracene (ăn`thrəsēn), C14H10, solid organic compound derived from coal tar. It melts at 218°C; and boils at 354°C;. , chrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno [1,2,3-cd]pyrene, dibenz[a,h]anthracene, and benzo[g,h,i]perylene (Camaan and Whyatt 2001; Perera et al. 2003).

To examine the representativeness of a single 48-hr monitoring, a subset of the Krakow cohort was monitored once each trimester trimester /tri·mes·ter/ (-mes´ter) a period of three months.

tri·mes·ter
n.
A period of three months.


Trimester
The first third or 13 weeks of pregnancy.
 (n = 72, 72, and 68, respectively). However, the entire NYC cohort was monitored once. Unlike for NYC subjects, personal exposure to pesticides was not monitored for the Krakow cohort, based on the low residential pesticide pesticide, biological, physical, or chemical agent used to kill plants or animals that are harmful to people; in practice, the term pesticide is often applied only to chemical agents.  use (Jedrychowski W, personal communication). Details of the blood sample collection for biomarker biomarker /bio·mark·er/ (bi´o-mahr?ker)
1. a biological molecule used as a marker for a substance or process of interest.

2. tumor marker.


bi·o·mark·er
n.
1.
 analysis have been reported (Perera et al. 2003; Rauh et al. 2004).

Statistical analysis. Our primary goal was to examine the consistency of the airborne PAH-birth outcome association in the Krakow and the NYC cohorts, respectively. Subsequently, the data from the two studies were merged to compare the association across the ethnic groups. In Krakow and NYC, subjects with complete data on personally monitored PAHs, birth outcomes, and potential confounding variables A confounding variable (also confounding factor, lurking variable, a confound, or confounder) is an extraneous variable in a statistical or research model that should have been experimentally controlled, but was not.  were included. To preclude selection bias, the demographic characteristics of those included versus not included were examined with analysis of variance (ANOVA anova

see analysis of variance.

ANOVA Analysis of variance, see there
) for the continuous variables, followed by Bonferroni correction In statistics, the Bonferroni correction states that if an experimenter is testing n independent hypotheses on a set of data, then the statistical significance level that should be used for each hypothesis separately is 1/n  and pair-wise chi-square test chi-square test: see statistics.  for categorical That which is unqualified or unconditional.

A categorical imperative is a rule, command, or moral obligation that is absolutely and universally binding.

Categorical is also used to describe programs limited to or designed for certain classes of people.
 variables. For both cohorts, the [SIGMA]8 c-PAHs was used as the independent variable because the PAHs were intercorrelated (Spearman's rho Spearman's rho,
n.pr a statistical test for correlation between two rank-ordered scales. It yields a statement of the degree of interdependence of the scores of the two scales.
 = 0.96-0.98).

We conducted the multivariate The use of multiple variables in a forecasting model.  linear regression Linear regression

A statistical technique for fitting a straight line to a set of data points.
 analysis using hierarchical backward elimination strategy (Kleinbaum and Klein 2002), while examining multicollinearity, multiple testing, and influential observations as possible sources of spurious spu·ri·ous
adj.
Similar in appearance or symptoms but unrelated in morphology or pathology; false.



spurious

simulated; not genuine; false.
 association. We conduction conduction, transfer of heat or electricity through a substance, resulting from a difference in temperature between different parts of the substance, in the case of heat, or from a difference in electric potential, in the case of electricity.  regression diagnostics before and after model specification. Influential observations (one African American and one Caucasian) were dropped. The birth outcomes, gestational age, cord cotinine, and [SIGMA]8 c-PAHs were natural-log (ln) transformed because their distributions significantly deviated from normality normality, in chemistry: see concentration.  (Kolmogorov-Smirnov test In statistics, the Kolmogorov–Smirnov test (often called the K-S test) is used to determine whether two underlying one-dimensional probability distributions differ, or whether an underlying probability distribution differs from a hypothesized distribution, in either  p-values < 0.001). The following categorical variables were created from the interview data: maternal education (< high school; high school graduate; > high school); high dietary intake of PAHs during current pregnancy (smoked, grilled, barbequed/blackened food items [greater than or equal to] 2/week); parity ([greater than or equal to] one prior singleton sin·gle·ton
n.
An offspring born alone.


singleton Medtalk One baby. Cf Triplet, Twin.
 or multiple births); any consumption of wine, beer, or hard liquor hard liquor A popular term for beverages with a high–often > 30% by volume–ie, 60 proof alcohol content–eg, gin, rum, vodka, whiskey; HLs are preferred by alcoholics as a steady state of low-level inebriation is easier to maintain. See Standard drink. , respectively; daily alcoholic intake ([greater than or equal to] one glass of wine, can of beer, or 2-oz shot of hard alcohol per day); marital status marital status,
n the legal standing of a person in regard to his or her marriage state.
 (married or cohabit co·hab·it  
intr.v. co·hab·it·ed, co·hab·it·ing, co·hab·its
1. To live together in a sexual relationship, especially when not legally married.

2. To coexist, as animals of different species.
 with same partner [greater than or equal to] 7 years), and maternal ETS exposure at home or at work ([greater than or equal to] one smoker smoker A person who smokes tobacco, almost always understood to be cigarettes Ratio of ♂:♀ smokers Philippines64/19, China61/7, Saudi Arabia53/2, Russia50/12 ; number of smokers; and number of cigarettes smoked in the woman's presence), and prepregnancy weight and height. The season of delivery was defined as fall (September-November), winter (December-February), and spring (March-May), using summer (June-August) as the reference. To further validate nonsmoking status, the subjects were restricted to those who had < 25 ng/mL cotinine in the umbilical cord serum. If the cord cotinine was below the limit of detection (LOD Lod (lōd), city (1994 pop. 51,200), central Israel. It is also known as Lydda. Its manufactures include paper products, chemicals, oil products, electronic equipment, processed food, and cigarettes. ) (0.025 ng/mL), the value of LOD/2 was attributed to that sample. Whenever the newborn's value was missing, the maternal level was used because there is a high correlation between cord and maternal blood concentrations.

We validated the reliability of the gestational age obtained from the infant's medical record by independently deriving the gestational age with date of last menstrual period last menstrual period Gynecology The most recent time that a ♀ notes menstruation, a datum recorded in a chart during a routine gynecologic visit. See Menstruation.  (LMP LMP left mentoposterior (position of fetus); last menstrual period.

LMP
abbr.
last menstrual period


LMP Last menstrual period, see there
) and/or sonogram son·o·gram
n.
An image, as of an unborn fetus, produced by ultrasonography. Also called echogram, sonograph, ultrasonogram.
. LMP-based gestational age was calculated as

[date of delivery - date of LMP] / 7 days,

and sonogram-based age as

[date of delivery - (expected date of delivery based on the sonogram - 280 days)] / 7 days.

In the Krakow cohort, the reliability of the original gestational age (n = 340), relative to LMP-based (n = 340) and sonogram-based (n = 165) gestational age, was examined through an analysis of internal consistency In statistics and research, internal consistency is a measure based on the correlations between different items on the same test (or the same subscale on a larger test). It measures whether several items that propose to measure the same general construct produce similar scores. . In the NYC cohort, the reliability of the original gestational age was compared by creating three mutually exclusive Adj. 1. mutually exclusive - unable to be both true at the same time
contradictory

incompatible - not compatible; "incompatible personalities"; "incompatible colors"
 groups--gestational age based on LMP alone (n = 90), based on sonogram alone (n = 137), or based on both (n = 130). Twenty-three NYC subjects, whose method of gestational age calculation is unknown, were not included in this analysis. We assessed the internal consistency of the original variable relative to derived ones by determining Spearman-Brown and Cronbach's [alpha] coefficients, respectively.

Considering the significant ethnic difference in PAH effect observed in our preliminary analysis (Perera et al. 2003) as well as the demographic differences of the mothers (Table 1), we conducted separate analyses for each ethnic group within their full exposure range. Potential confounders identified from the literature were included in the multivariate models if they were related to birth weight, length, or head circumference (p < 0.05) or if their absence significantly affected the estimated PAH effect ([greater than or equal to] 10% change) (Greenland 1989).

We also compared the association between the NYC and Krakow cohorts. Because the mean exposure levels between NYC and Krakow cohorts differed by > 10-fold, we selected a subset whose prenatal PAH exposure level lay within the range common to both cohorts (1.80-36.47 ng/[m.sup3]) [n =123 African Americans (73%), 161 Dominicans (76%), and 227 Caucasians (67%)]. The possibility that the PAH effects differ according to according to
prep.
1. As stated or indicated by; on the authority of: according to historians.

2. In keeping with: according to instructions.

3.
 the gestational age at the time of monitoring was addressed by comparing birth outcome models for the Krakow subjects monitored in the second versus the third trimester. We also examined whether ethnic groups are differentially exposed to other toxicants that are correlated with sociodemographic conditions. Namely, although a common residential pesticide, chlorpyrifos (CPF (Control Program Facility) The IBM System/38 operating system that included an integrated relational DBMS. ), has been shown to reduce fetal growth in NYC (Whyatt et al. 2004), prenatal CPF exposure is believed to be minimal in Krakow (Jedrychowski W, personal communication). We examined the correlation between PAHs and CPF within the NYC cohort, and found it to be low (p > 0.1). Furthermore, dropping CPF from the birth weight and birth head circumference models, respectively, did not affect the size of PAH effect for NYC African Americans, indicating that it is unlikely to be a confounder con·found  
tr.v. con·found·ed, con·found·ing, con·founds
1. To cause to become confused or perplexed. See Synonyms at puzzle.

2.
 (Perera et al. 2003). Finally, possible residual confounding confounding

when the effects of two, or more, processes on results cannot be separated, the results are said to be confounded, a cause of bias in disease studies.


confounding factor
 by each sociodemographic variable shown in Table 1 was considered if it met the criteria for potential cofounders.

In combined analyses, we tested the hypothesis that there is no significant difference in PAH effect across ethnic groups by including indicator variables for the African-American, the Dominican, and interaction terms (NYC African American x PAH, and NYC Dominican x PAH). We considered Caucasians the reference group because our interest lay in quantifying the difference between the Krakow cohort and each NYC ethnic group.

The PAH-birth outcome association for each cohort group was visualized by creating adjusted scatterplots for the three birth outcomes. The residual variance Residual variance or unexplained variance is part of the variance of any residual. The other part is explained variance. In analysis of variance and regression analysis, residual variance is that part of the variance which cannot be attributed to specific causes.  on the y-axis is plotted against the PAH exposure on the x-axis for each ethnic group. The model controlled for (ln) gestational age, newborn newborn /new·born/ (noo´born?)
1. recently born.

2. newborn infant.


new·born
adj.
Very recently born.

n.
A neonate.
 sex, maternal prepregnancy weight, height, parity, and delivery fall, winter, and spring, respectively [Table S3(A) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)]. The adjusted scatterplots were generated first for the overall exposure range of each city [Figure S1 in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)], and subsequently, within the exposure range common between the two cities (Figure 1). All analyses, including adjusted scat-terplots, were conducted in SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance.  for Windows (version 11.5; SPSS Inc., Chicago, IL, USA).

Results

Descriptive analysis. Table 1 shows the demographic and exposure characteristics of the mothers and the birth outcomes. The 340 Krakow subjects included are similar to those not included (23 women who refused before the onset of the study, 57 women lost to follow-up, and 67 women with incomplete, missing, or poor-quality data) with respect to household income, maternal age maternal age,
n the age of the mother at the period of conception.
, prepregnancy weight, height, ETS exposure, and education (p > 0.05) [Table S1(A) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)].

Among 687 fully enrolled NYC women (243 African Americans, 442 Dominicans, 2 with unknown ethnic background), valid PAH data were available for 534 mothers; 10 cases had cord cotinine level > 25 ng/mL; birth weight measurements were available for 448 newborns; birth length measurements were available for 436 newborns; and birth head circumference measurements were available for 425. No significant differences were observed in [SIGMA]8 c-PAHs, mother's age, education level, prepregnancy weight, marital status, daily alcohol intake, frequent intake of PAH-containing foods, and ETS exposure between subjects with missing data and those included [Table S1(B) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)].

In Krakow, prevalence of low birth weight (LBW LBW Low birth weight, see there ; < 2,500 g) and preterm preterm /pre·term/ (-term´) before completion of the full term; said of pregnancy or of an infant.

pre·term
adj.
 birth (< 37 weeks of gestation) were 3.5 and 4.7%, respectively. In NYC, the prevalence of LBW in African-Americans and Dominicans was 6.2 and 2.1%, respectively; and the prevalence of preterm birth was 6.8 and 2.2%, respectively.

Although the study targeted nonsmoking women, we sought to control further for potential confounding by prenatal ETS exposure by using the umbilical cord cotinine level and the women's self-reported ETS exposure. Between the second- and the third-trimester interviews in the Krakow cohort, the number of smokers at home remained highly consistent (intraclass correlation In statistics, the intraclass correlation (or the intraclass correlation coefficient[1]) is a measure of correlation, consistency or conformity for a data set when it has multiple groups.  coefficient = 0.81, p < 0.001). The level of prenatal exposure to ETS was low in all three cohorts (Table 1). Among the Krakow cohort, cord cotinine was low, but dose dependent (0.15 [+ or -] 0.32 among nonsmokers vs. 0.84 [+ or -] 1.60, 0.92 [+ or -] 0.93, and 2.62 [+ or -] 3.42 ng/mL, among those with one, two, or three smokers at home, respectively) based on the third-trimester questionnaire (Spearman's rho = 0.391, p = 0.006). Cord cotinine level was not dose dependent in African Americans (0.72 [+ or -] 1.66 ng/mL with one smoker; 0.31 [+ or -] 0.22 ng/mL with two; 0.64 [+ or -] 3.56 ng/mL with three; 0.43 [+ or -] 0.38 ng/mL with four; Spearman's rho = 0.16, p = 0.25) and in Dominicans (0.33 [+ or -] 1.25 ng/mL with one smoker; 0.19 [+ or -] 0.35 ng/mL with two; 0.16 [+ or -] 0.20 ng/mL with three; Spearman's rho = 0.072, p = 0.63). The mother's self-reported ETS exposure, the umbilical cord plasma cotinine level, frequent dietary PAH intake, any exposure to alcohol during the entire pregnancy, and daily alcoholic intake were not associated with any of the outcomes in the respective ethnic groups.

In the Krakow cohort, mean LMP-based gestational age was 40 [+ or -] 2 weeks (range, 29-43). Mean sonogram-based gestational age was 40 [+ or -] 1 (range, 34-45). Cronbach's [alpha] reliability coefficient of the original, LMP-based, and sonogram-based gestational age was 0.90, suggesting a high reliability of the infant's medical record data. Among the NYC cohort, the reliability of the internal consistency of the original gestational age differed according to the mode of derivation derivation, in grammar: see inflection. . For those whose gestational age was derived with LMP date (n =90), Cronbach's [alpha] and Spearman-Brown was 0.78 and 0.83, respectively. For those whose gestational age was determined by sonogram (n = 137), Cronbach's [alpha] and Spearman-Brown reliability coefficients were both 0.90. Among those whose gestational age was estimated using both LMP and sonogram (n = 130), both coefficients were 0.94. For the remaining 23 newborns, reliability of the gestational age could not be determined because LMP and sonogram data were missing. Prenatal PAH exposure for the missing group did not differ significantly from the remaining groups (p-value for ANOVA > 0.05). As a result, the original gestational age variable was used.

Risk of prenatal exposure to PAHs on birth weight, birth length, and birth head circumference. To compare the size of the PAH effect between the Krakow and NYC cohorts, we included the same set of confounders--gestational age, baby's sex, parity, maternal prepregnancy weight, height, and season of delivery--in the final multivariate model (Table 2). Delivery by cesarean section cesarean section (sĭzâr`ēən), delivery of an infant by surgical removal from the uterus through an abdominal incision. The operation is of ancient origin: indeed, the name derives from the legend that Julius Caesar was born in this  protects against birth head circumference reduction, and was included in the birth head circumference model. Mother's age, mother's educational level, any exposures to ETS at home or at work, maternal dietary intake of PAH-containing foods at least twice a week, marital status, any exposure to wine, beer, or hard liquor, respectively, or daily intake of alcohol did not meet the criteria for inclusion in the model. Although particulate matter particulate matter
n. Abbr. PM
Material suspended in the air in the form of minute solid particles or liquid droplets, especially when considered as an atmospheric pollutant.

Noun 1.
 < 2.5 [micro]m in aerodynamic diameter Drug particles for pulmonary delivery are typically characterized by aerodynamic diameter rather than geometric diameter. The velocity at which the drug settles is proportional to the aerodynamic diameter, da.  (P[M.sub.2.5]) and season of personal air monitoring might be independent risk factors (Jedrychowski et al. 2004), we could not control for either variable because of the high variance inflation factor The Variance Inflation Factor (VIF) is a method of detecting the severity of Multicollinearity. More precisely, the VIF is an index which measures how much the variance of a coefficient(square of the standard error) is increased because of collinearity.  induced by these variables.

In the Krakow cohort, prenatal exposure to PAHs was significantly associated with reduced birth weight ([beta] = -0.020, p < 0.01; weight decrement To subtract a number from another number. Decrementing a counter means to subtract 1 or some other number from its current value.  = 68.75 g/ln-unit of exposure), birth length ([beta] = -0.009, p < 0.01; length decrement = 0.48 cm/ln-unit), and birth head circumference ([beta] = -0.006, p = 0.01; head circumference decrement = 0.21 cm/ln-unit) (Table 2). In the NYC cohort prenatal exposure to PAHs was associated with reduced (ln) birth weight ([beta] = -0.06; gram decrement = 177.57 g/ln-unit, p < 0.01) among NYC African Americans, but not among NYC Dominican (p > 0.1) (Table 2). In the NYC cohort, stratified stratified /strat·i·fied/ (strat´i-fid) formed or arranged in layers.

strat·i·fied
adj.
Arranged in the form of layers or strata.
 regression of the PAH effect according to the median CPF value was conducted. For NYC AA, the PAH effect remained similar ([beta] = -0.063 for < median CPF level; [beta] = -0.061 for [greater than or equal to] median CPF level). As shown in a prior analysis (Perera et al. 2003), exclusion of CPF from the model did not affect the estimated size of PAH effect (change in PAH effect < 3%), indicating that CPF is neither a significant effect modifier (programming) modifier - An operation that alters the state of an object. Modifiers often have names that begin with "set" and corresponding selector functions whose names begin with "get".  nor a confounder.

Prenatal exposure to PAHs was not associated with a significant reduction in gestational age either for the Krakow cohort ([beta] = -0.002, p = 0.28) or for the NYC cohort ([beta] for African American = -0.005, p = 0.32; [beta] for Dominican = 0.003, p = 0.32).

Comparative analysis of PAH effects between the two cohorts. Table 1 shows that Caucasians and African Americans differ significantly in mother's age, prepregnancy weight, height, highest completed education, marital status, parity, ETS exposure, dietary PAH intake, any alcohol intake during the current pregnancy, maternal personal PAHs exposure level, and cord cotinine concentration.

In exploratory analyses, both Krakow and NYC samples were restricted to those within the PAH exposure range common between the two cohort studies (1.80-36.47 ng/[m.sup.3]). The size of PAH effects for the Krakow cohort were identical ([beta] = -0.021 for birth weight; [beta] = -0.009 for birth length; [beta] = -0.008 for birth head circumference) to the estimates based on the overall range, though not significant (all p-values > 0.05) (Table 3). For NYC African Americans within the common range, the effect was larger ([beta] = -0.085, p = 0.003 for birth weight; [beta] = -0.023, p = 0.03 for birth head circumference) than the estimates based on the cohort's overall range (0.27-36.47 ng/[m.sup.3]) (Table 3). The difference in PAH effect size between the cohorts was determined over the entire range (0.27-272.18 ng/[m.sup.3]) [Figure S1 in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)] and within the common exposure range (1.80-36.47 ng/[m.sup.3]) (Figure 1). The models included relevant covariates, including those that differed between ethnic groups. Across the common exposure range, the effect per ln-unit increase in exposure was significantly greater for African Americans than for Caucasians for birth weight ([beta] for difference in PAH effect = -0.062, p = 0.01) and marginally greater for birth head circumference ([beta] for difference in PAH effect = -0.015, p = 0.07) (Figure 1). Similarly, across the overall exposure range, the effect of prenatal PAH exposure was significantly greater on the birth weight of African Americans ([beta] for difference in PAH effect for birth weight = -0.043, p = 0.01) [Figure S1 and Table S3(A) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)]. The adjusted scatter-plot for birth weight (Figure 1) illustrates that with increasing PAH exposure level, NYC African Americans experienced a significantly greater reduction in birth weight than Caucasians. There were no significant differences in the magnitude of the PAH effect between NYC Dominicans and Caucasians for any of the birth outcomes. For birth length and the birth head circumference, a unit increase in prenatal PAH exposure level did not result in a significantly greater effect in the NYC African Americans.

The effects of prenatal exposure to PAHs on birth weight ([beta] = -0.017, p = 0.09), birth length ([beta] = -0.011, p < 0.01), and birth head circumference ([beta] = -0.008, p < 0.01) among the subset of 202 Krakow mothers who were monitored in the third trimester were very similar to those estimated in the second trimester Noun 1. second trimester - time period extending from the 13th to the 27th week of gestation
trimester - a period of three months; especially one of the three three-month periods into which human pregnancy is divided
 [Table S4(A) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)]. Furthermore, comparison of maternal demographic characteristics among these participants within the exposure range of interest (1.80-36.47 ng/[m.sup.3]) versus those outside (> 36.47 ng/[m.sup.3] for Krakow and < 1.80 ng/[m.sup.3] for NYC samples) demonstrated no significant difference [Table S1(C) in Supplemental Materials (http://www.ehponline.org/docs/2006/8982/suppl.pdf)].

Discussion

In two separate but parallel prospective cohort studies, in utero exposure to airborne PAHs was significantly associated with adverse effects on fetal growth in both Polish Caucasians and U.S. African Americans. There was a significant association between airborne PAHs and birth outcomes in two locations across a 10-fold exposure range. These findings are of concern because reduced birth weight has been associated with greater risks of fetal and neonatal mortality Noun 1. neonatal mortality - the death rate during the first 28 days of life
neonatal mortality rate

death rate, deathrate, fatality rate, mortality rate, mortality - the ratio of deaths in an area to the population of that area; expressed per 1000 per year
 (Wen et al. 2005), delay in cognitive development (Rice and Barone 2000; Richards et al. 2002), and increased risk of type II diabetes Type II diabetes
Type II diabetes is the most common form of diabetes and usually appears in middle aged adults. It is often associated with obesity and may be delayed or controlled with diet and exercise.

Mentioned in: Diabetic Ketoacidosis
, hypertension, and coronary heart disease coronary heart disease: see coronary artery disease.
coronary heart disease
 or ischemic heart disease

Progressive reduction of blood supply to the heart muscle due to narrowing or blocking of a coronary artery (see atherosclerosis).
 during adulthood (Barker 2002).

The two studies targeted women with adequate prenatal care prenatal care,
n the health care provided the mother and fetus before childbirth.
, free from diabetes, hypertension, or HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. , nonsmokers of cigarettes and nonusers of illicit drugs to preclude confounding of the PAH-birth outcome associations. Both Krakow and NYC cohort mothers are representative of the target population. Within both cohorts, the demographic traits of the women who agreed to participate, refused, were lost to follow-up, and remained in the current study are very similar, suggesting that selection bias is unlikely to have occurred. In addition, maternal demographic characteristics of those within the lower exposure range (1.80-36.47 ng/[m.sup.3]) were similar to those excluded, demonstrating that selection bias does not account for the apparent difference in PAH-birth outcome between the ethnic groups.

The prevalence of LBW among the current NYC African-American sample was about half of the prevalence generally among U.S. African Americans (7 vs. 13%) (David and Collins 1997). The low incidence of LBW and preterm birth in both cohorts reflect the eligibility criteria and indicate that the women included in the current study are representative of lower-risk pregnant women rather than the general population. As a mounting body of evidence suggests, among pregnant women who have additional risk factors, the risk of prenatal PAH exposure on fetal growth might be considerably greater (Erickson et al. 1999; Wormley et al. 2004).

The observation that there was a significantly greater effect among NYC African Americans than among Krakow Caucasians when the analysis was restricted to a lower common range of exposure suggests increased susceptibility of the former population. The same effect was not seen in NYC Dominicans. We examined whether ETS (both self-reported and cord plasma cotinine), spousal support spousal support n. payment for support of an ex-spouse (or a spouse while a divorce is pending) ordered by the court. More commonly called alimony, spousal support is the term used in California and a few other states as part of new non-confrontational language (such , educational level, frequent consumption of dietary PAHs, and foreign birth might explain the difference in associations across the ethnic groups. Each of these factors was neither an effect modifier nor a source of confounding in the current analysis. Although we did not ask about dairy, fruit, fish, and vegetable consumption during pregnancy, prenatal vitamin intake was high in all three groups (87% of Dominicans, 96% of African Americans, and 100% of Caucasians). However, neighborhood factors such as social isolation, crime, and poverty were not examined, and these might have confounded the current association. It is also possible that other components of P[M.sub.2.5] or the differential proportion of the carcinogenic PAHs between two cities might have confounded the outcomes.

Other studies have previously observed a greater effect of air pollution experienced by racial minorities and those of lower socioeconomic status socioeconomic status,
n the position of an individual on a socio-economic scale that measures such factors as education, income, type of occupation, place of residence, and in some populations, ethnicity and religion.
 (Ito and Thurston 1996; Jerrett et al. 2004). In this analysis, NYC African Americans were of lower socioeconomic status (in education) than Krakow Caucasians and were significantly less likely to be married (hence had less social support). They also had prenatal co-exposure to the fetotoxic pesticide chlorpyrifos (Whyatt et al. 2004), whereas Krakow Caucasians did not. Although lack of adequate prenatal care could not have confounded the outcome, we did not examine history of previous LBW.

Adverse effects seen in NYC African Americans were not evident in NYC Dominicans with comparable prenatal exposure to PAHs. Although the two NYC groups are similar with respect to income and education, they differ significantly in other demographic factors such as current marital status, with NYC Dominican more likely to be married. NYC African Americans also have greater co-exposure to chlorpyrifos (Whyatt et al. 2004). Moreover, NYC African Americans differ from NYC Dominicans in that 77% of the Dominican women were born outside of the United States United States, officially United States of America, republic (2005 est. pop. 295,734,000), 3,539,227 sq mi (9,166,598 sq km), North America. The United States is the world's third largest country in population and the fourth largest country in area. . Other research suggests that less acculturated Hispanic immigrants might be at lower risk of adverse birth outcomes as well as adulthood morbidities (Flores Flores, town, Guatemala
Flores (flōrəs), town (1990 est. pop. 2,200), capital of Petén department, N Guatemala. Flores was built on an island in the southern part of Lake Petén Itzá and on the site of the
 and Brotanek 2005). Similarly, among low-risk women, prevalence of having an LBW newborn among African-born black women (3.6%) was much lower than for U.S.-born black women (7.5%) (David and Collins 1997). In our cohort study, compared with the newborns from U.S.-born Dominican mothers, the newborns from the recent immigrant Dominican mothers had a higher birth weight (3,466 vs. 3,358 g, p = 0.1) and birth length (51.11 vs. 49.62 cm, p = 0.003).

The observed differences between ethnic groups may also result from unmeasured contextual factors or from gene-environment interactions Gene-environment interaction is a term used to describe any phenotypic effects that are due to interactions between the environment and genes. Naive nature versus nurture debates assume that variation in a given trait is primarily due to either genes, or the individual's  (Wiencke 2004). In the present analysis, data on genetic polymorphisms were not available, nor would the sample size permit a meaningful analysis of interactions. In the current analysis, the low number of LBW cases prevented examination of the risk associated with prenatal PAH exposure. Larger studies are needed to determine the genetic, environmental, and/or socioeconomic so·ci·o·ec·o·nom·ic  
adj.
Of or involving both social and economic factors.


socioeconomic
Adjective

of or involving economic and social factors

Adj. 1.
 factors underlying the observed ethnic differences in the effects of transplacental transplacental /trans·pla·cen·tal/ (-plah-sen´tal) through the placenta.

trans·pla·cen·tal
adj.
Relating to or involving passage through or across the placenta.
 PAH exposure.

Prior studies have suggested that diesel fuel combustion contributes to ambient PAHs in NYC (Tonne et al. 2004), whereas coal burning in small furnaces is a major source of PAHs in Krakow (Lvovsky et al. 2000). We examined whether differences in the proportion of individual PAHs in the air might account for the difference in the birth outcomes by conducting the same regression for each of the eight individual carcinogenic PAHs within the common exposure range. Prenatal exposure to benzo[g,h,i]perylene was associated with the largest difference (7-fold) in PAH effect among NYC African Americans compared with Krakow Caucasians. Next were benzo[b]fluoranthene and indeno[1,2,3-c,d]pyrene, which were each associated with a 5-fold greater effect among African Americans. In NYC, these three PAHs are the most common PAHs (constituting 19, 9, and 10%, respectively, of the eight carcinogenic PAHs). In contrast, in Krakow the relative proportions of each carcinogenic PAH were equal among the eight carcinogenic PAHs. BaP was associated with a 3-fold greater effect for NYC African Americans compared with Krakow Caucasians. BaP was the fourth most common PAH (7%) in NYC, whereas in Krakow, it was the second most common PAH (16%). Prior studies have shown that benzo[g,h,i]perylene and ideno[1,2,3-c,d]pyrene are predominant PAHs from gasoline combustion (Binkova et al. 2003). Embryotoxic activity of dichloromethane extractable organic matter was highest for those collected from the Prague city center with high traffic volume (Binkova et al. 2003).

Because PAH effects on fetal growth could differ depending on the timing of exposure (Dejmek et al. 2000), we used Krakow data to consider whether nondifferential exposure misclassification of the exposure during unmeasured gestational gestational

pertaining to or emanating from gestation.


gestational age
the age of the fetus in terms of time lapse, e.g. three month fetus, or in terms of proportion of total gestational duration, e.g. first trimester fetus.
 months threatens the validity of the PAH-fetal growth association. We observed that indicator variables for season of monitoring are the most significant predictors of the personal exposure level of [SIGMA]8 c-PAHs ([R.sup.2] = 0.723) in the Krakow cohort (n = 340). However, considering the high correlation between seasons of monitoring and the main exposure variable, season of delivery was chosen as an alternative covariate. Multicollinearity of season of delivery and the main exposure was quite low (variance inflation factor of the involved variables < 3). The estimated PAH risk remained identical whether exposure during unmeasured gestational trimester was accounted for by a modeled exposure variable or by indicator variables for delivery season.

Strengths of the study include the validation of self-reported nonsmoking status with cord cotinine level. Positive agreement between ETS and umbilical cord cotinine level in both cohorts precludes PAH exposure misclassification and potential confounding by ETS. A high proportion of Krakow Caucasian women reported that they had at least one glass of wine during the current pregnancy (52%), although the prevalence of daily alcoholic intake was extremely low in all three ethnic groups. Neither "any" exposure to alcohol during the entire pregnancy, "daily" alcoholic intake, nor dietary intake of PAHs had a significant effect on the three birth outcomes.

Mechanisms of fetal toxicity of PAHs are not fully understood but may involve the induction of apoptosis apoptosis
 or programmed cell death

Mechanism that allows cells to self-destruct when stimulated by the appropriate trigger. It may be initiated when a cell is no longer needed, when a cell becomes a threat to the organism's health, or for other reasons.
 after DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 damage from PAHs, antiestrogenic effects of PAHs, and binding to the human aryl hydrocarbon receptor The Aryl hydrocarbon receptor (AhR) is member of the family of basic-helix-loop-helix transcription factors. AhR is a cytosolic transcription factor that is normally inactive, bound to several co-chaperones.  to induce P450 enzymes or to receptors for placental placental

pertaining to or emanating from placenta.


placental barrier
the placental separation of maternal and fetal blood which varies in its structure and permeability between the species.
 growth factors, resulting in decreased exchange of oxygen and nutrients (Dejmek et al. 2000).

Given that PAH concentrations in Krakow and NYC are representative of the range seen in much of the developing and industrialized in·dus·tri·al·ize  
v. in·dus·tri·al·ized, in·dus·tri·al·iz·ing, in·dus·tri·al·iz·es

v.tr.
1. To develop industry in (a country or society, for example).

2.
 world, reduction of transplacental exposure to PAHs would be expected to have both short-term and long-term benefits to health worldwide. Fossil fuel and wood combustion are the primary sources of ambient PAHs (Bostrom et al. 2002) and are a major source of greenhouse gases greenhouse gas
n.
Any of the atmospheric gases that contribute to the greenhouse effect.



greenhouse gas 
 that impact the global climate (National Academy of Sciences 2001). It has been estimated that mitigation of these emissions by using readily available technologies would yield substantial health benefits to 3 billion urban residents worldwide (Cifuentes et al. 2001; Levy et al. 2002). The associated economic benefits of reducing fossil fuel-related air pollution are estimated to amount to a savings of many billions of dollars each year in the United States alone (Wong et al. 2004). Thus, policies to reduce ambient concentrations of PAHs should yield substantial benefits to human health and the global environment.

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Perera FP, Whyatt RM, Jedrychowski W, Rauh V, Manchester D, Santella RM, et al. 1998. Recent developments in molecular epidemiology molecular epidemiology Molecular medicine An evolving field that combines the tools of standard epidemiology–case studies, questionnaires and monitoring of exposure to external factors with the tools of molecular biology–eg, restriction endonucleases, : a study of the effects of environmental polycyclic aromatic hydrocarbons on birth outcomes in Poland. Am J Epidemiol 147:309-314.

Rauh VA, Whyatt RM, Garfinkel R, Andrews H, Hoepner L, Reyes A, et al. 2004. Developmental effects of exposure to environmental tobacco smoke and material hardship among innercity children. Neurotoxicol Teratol 26:373-385.

Rice D, Barone S Jr. 2000. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 108:511-533.

Richards M, Hardy R, Kuh D, Wadsworth ME. 2002. Birth weight, postnatal postnatal /post·na·tal/ (-na´t'l) occurring after birth, with reference to the newborn.

post·na·tal
adj.
Of or occurring after birth, especially in the period immediately after birth.
 growth and cognitive function cognitive function Neurology Any mental process that involves symbolic operations–eg, perception, memory, creation of imagery, and thinking; CFs encompasses awareness and capacity for judgment  in a national UK birth cohort. Int J Epidemiol 31:342-348.

Sram RJ, Binkova B, Dejmek J, Bobak M. 2005. Ambient air pollution and pregnancy outcomes: a review of the literature. Environ Health Perspect 113:375-382.

Tonne C, Whyatt RM, Camann DE, Perera FP, Kinney PL. 2004. Predictors of personal polycyclic aromatic hydrocarbon exposures among pregnant minority women in New York City. Environ Health Perspect 112:754-759.

Vassilev ZP, Robson MG, Klotz JB. 2001. Associations of polycyclic organic matter in outdoor air with decreased birth weight: a pilot cross-sectional analysis Cross-sectional analysis

Assessment of relationships among a cross-section of firms, countries, or some other variable at one particular time.
. J Toxicol Environ Health Part A 64:595-605.

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dis·cor·dance
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Any of a large group of substances used to kill insects. Such substances are mainly used to control pests that infest cultivated plants and crops or to eliminate disease-carrying insects in specific areas.
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Hyunok Choi, (1) Wieslaw Jedrychowski, (2) John Spengler, (3) David E. Camann, (4) Robin M. Whyatt, (1) Virginia Rauh, (1) Wei-Yann Tsai, (5,6) and Frederica P. Perera (1)

(1) Columbia Center
You may be looking for the Columbia Center in Troy, MI or Columbia Center Mall in Kennewick, WA.


The Columbia Center (formerly the Bank of America Tower, Columbia Center and the Columbia Seafirst Center
 for Children's Environmental Health, Mailman School of Public Health, Columbia University Columbia University, mainly in New York City; founded 1754 as King's College by grant of King George II; first college in New York City, fifth oldest in the United States; one of the eight Ivy League institutions. , New York, New York, USA; (2) Epidemiology and Preventive Medicine preventive medicine, branch of medicine dealing with the prevention of disease and the maintenance of good health practices. Until recently preventive medicine was largely the domain of the U.S. , College of Medicine, Jagiellonian University, Krakow, Poland; (3) Department of Environmental Health, Harvard School of Public Health The Harvard School of Public Health is (colloquially, HSPH) is one of the professional graduate schools of Harvard University. Located in Longwood Area of the Boston, Massachusetts neighborhood of Mission Hill, next to Harvard Medical School and Cambridge, Massachusetts, , Boston, Massachusetts “Boston” redirects here. For other uses, see Boston (disambiguation).
Boston is the capital and most populous city of Massachusetts.[3] The largest city in New England, Boston is considered the unofficial economic and cultural center of the entire New
, USA; (4) Department of Analytical and Environmental Chemistry, Southwest Research Institute, San Antonio, Texas “San Antonio” redirects here. For other uses, see San Antonio (disambiguation).
San Antonio is the second most populous city in Texas, the third most populous metropolitan area in Texas, and is the seventh most populous city in the United States. As of the 2006 U.S.
 USA; (5) Department of Biostatistics biostatistics /bio·sta·tis·tics/ (-stah-tis´tiks) biometry.

bi·o·sta·tis·tics
n.
The science of statistics applied to the analysis of biological or medical data.
, Mailman School of Public Health, Columbia University, New York, New York, USA; (6) Department of Statistics, National Cheng Kung University National Cheng Kung University (Traditional Chinese: 國立成功大學; Simplified Chinese: 国立成功大学 , Taiwan

Address correspondence to F.P. Perera, Columbia Center for Children's Environmental Health, Mailman School of Public Health, Columbia University, 100 Haven Ave., #25F, Tower 3, New York, NY 10032 USA. Telephone: (212) 304-7280. Fax: (212) 544-1943. E-mail: fpp1@columbia.edu

Supplemental material is available online at http://www.ehponline.org/docs/2006/8982/suppl.pdf

H. Andrews, I. Bendkowska, M. Borjas, D. Diaz, E. Evans, E. Flak, R. Garfinkel, L. Hoepner, P. Kinney, E. Masters, E. Mroz, A. Pac, B. Plaza, C. Pulgarin, L. Qu, J. Ramirez, A. Reyes, E. Sochacka-Tatara, and Y. Tu collaborated on this research.

The authors declare they have no competing financial interests.

Received 6 January 2006; accepted 3 August 2006.
Table 1. Demographic and exposure characteristics and pregnancy outcomes
of the study cohorts.

Demographic variables                Krakow Caucasians (n = 340)

Maternal age (years)                    28 [+ or -] 4 (18-36)*
Prepregnancy weight (kg)                58 [+ or -] 9 (40-118)
Maternal height (cm)                   165 [+ or -] 6 (144-180)
Maternal education [n (%)]
  < High school                         36 (11)
  High school graduate                  90 (27)
  > High school                        214 (63)*
Currently married [n (%)]              316 (93)*
Parity [n (%)]                         118 (35)
ETS exposure at home or work           131 (39)
  [n (%)]
Any alcohol intake [n (%)]
  Wine                                 175 (52)
  Beer                                 107 (32)
  Hard liquor                           21 (6)
Daily alcohol intake [n (%)]             4 (1)
Frequent intake of PAH-containing       49 (14)
  foods [n (%)]
Taken prenatal vitamin during          340 (100)
  current pregnancy [n (%)]
Household income [n (%)]
  < $10,000
    $10,000-20,000
    $20,001-50,000
  > $50,000
  Not reported
Polish tax group (a) [n (%)]
  < 37,024 PLZ                         229 (67)
    37,024-74,048 PLZ                   16 (5)
  > 74,048 PLZ                           4 (1)
  Not reported                          91 (27)
Have U.S. Medicaid [n (%)]
Maternal personal exposure to           39.05 [+ or -] 47.63
  [SIGMA]8 c-PAHs (ng/[m.sup.3])        (1.80-272.18)*
Umbilical cord cotinine (ng/mL) (b)      0.32 [+ or -] 0.88 (0.01-8.45)
                                           [n = 227]
Newborn sex (female) [n (%)]           174 (51)
Birth weight (g)                     3,427 [+ or -] 493 (1,160-4,700)
Birth length (cm)                       54.5 [+ or -] 3.0 (37.0-64.0)*
Birth head circumference (cm)           33.9 [+ or -] 1.5 (26.0-39.0)
Gestational age (week) (c)              39 [+ or -] 2 (29-43)
Cesarean-section delivery [n (%)]       64 (19)*

Demographic                          NYC African Americans (n = 168)

Maternal age (years)                    24 [+ or -] 5 (18-36)
Prepregnancy weight (kg)                74 [+ or -] 20 (44-149)*
Maternal height (cm)                   164 [+ or -] 9 (132-183)
Maternal education [n (%)]
  < High school                         54 (32)
High school graduate                    74 (44)
  > High school                         40 (24)
Currently married [n (%)]               21 (13)
Parity [n (%)]                         139 (82)*
ETS exposure at home or work            88 (52)*
  [n (%)]
Any alcohol intake [n (%)]
  Wine                                  13 (8)
  Beer                                   8 (2)
  Hard liquor                           10 (6)
Daily alcohol intake [n (%)]             0 (0)
Frequent intake of PAH-containing       54 (32)*
  foods [n (%)]
Taken prenatal vitamin during          161 (96)
  current pregnancy [n (%)]
Household income [n (%)]
  < $10,000                             64 (38)
    $10,000-20,000                      48 (29)
    $20,001-50,000                      47 (28)
  > $50,000                              3 (2)
  Not reported                           6 (4)
Polish tax group (a) [n (%)]
  < 37,024 PLZ
    37,024-74,048 PLZ
  > 74,048 PLZ
  Not reported
Have U.S. Medicaid [n (%)]             143 (86)
Maternal personal exposure to            3.34 [+ or -] 2.92 (0.52-22.10)
  [SIGMA]8 c-PAHs (ng/[m.sup.3])
Umbilical cord cotinine (ng/mL) (b)      0.36 [+ or -] 0.95 (0.01-8.79)
                                           [n = 122]
Newborn sex (female) [n (%)]            83 (49)
Birth weight (g)                     3,302 [+ or -] 519* (1,875-5,110)
Birth length (cm)                       50.8 [+ or -] 3.1 (34.0-67.5)
Birth head circumference (cm)           33.8 [+ or -] 1.8 (28.0-37.5)
Gestational age (week) (c)              39 [+ or -] 2 (30-42)
Cesarean-section delivery [n (%)]        9 (5)

Demographic                          NYC Dominicans (n = 212)

Maternal age (years)                    25 [+ or -] 5 (18-38)
Prepregnancy weight (kg)                63 [+ or -] 13 (40-112)
Maternal height (cm)                   161 [+ or -] 8 (127-178)*
Maternal education [n (%)]
  < High school                         71 (35)
High school graduate                    87 (42)
  > High school                         48 (23)
Currently married [n (%)]               66 (31)
Parity [n (%)]                         142 (67)
ETS exposure at home or work            81 (38)
  [n (%)]
Any alcohol intake [n (%)]
  Wine                                  21 (10)
  Beer                                  43 (20)
  Hard liquor                           16 (8)
Daily alcohol intake [n (%)]             4 (2)
Frequent intake of PAH-containing       30 (14)
  foods [n (%)]
Taken prenatal vitamin during          185 (87)
  current pregnancy [n (%)]
Household income [n (%)]
  < $10,000                             99 (47)
    $10,000-20,000                      53 (25)
    $20,001-50,000                      29 (14)
  > $50,000                             17 (8)
  Not reported                          14 (7)
Polish tax group (a) [n (%)]
  < 37,024 PLZ
    37,024-74,048 PLZ
  > 74,048 PLZ
  Not reported
Have U.S. Medicaid [n (%)]             195 (92)
Maternal personal exposure to            3.72 [+ or -] 3.90 (0.27-36.47)
  [SIGMA]8 c-PAHs (ng/[m.sup.3])
Umbilical cord cotinine (ng/mL) (b)      0.18 [+ or -] 0.87 (0.01-7.75)
                                           [n = 157]
Newborn sex (female) [n (%)]           112 (53)
Birth weight (g)                     3,439 [+ or -] 451 (2,125-4,560)
Birth length (cm)                       50.76 [+ or -] 3.1 (19.0-56.5)
Birth head circumference (cm)           34.3 [+ or -] 1.3 (29.0-37.5)*
Gestational age (week) (c)              40 [+ or -] 1 (34-44)*
Cesarean-section delivery [n (%)]       27 (13)

Values are mean [+ or -] SD except where indicated.
(a) For 2005, the mean exchange rate was 1 Euro = 4.2009 Poland Zlotych
(PLZ); (b) Subjects with completed laboratory analysis as of September
2004. (c) Gestational age was calculated using LMP and sonogram data,
whenever available. *Significantly differs from the remaining two groups
based on ANOVA followed by Bonferroni correction or pair-wise
[chi square] test.

Table 2. Risk of reduced birth outcomes due to prenatal airborne PAH
exposure.

                                    (ln) Birth weight
                                    [beta]  SE     p-Value

Krakow Caucasian (n = 340)          Adjusted [R.sup.2] = 0.486
  (Constant)                        -1.131  0.563  0.046
  (ln) [SIGMA]8 c-PAHs              -0.020  0.007  0.007
  Maternal height                    0.003  0.001  0.019
  Prepregnancy weight                0.003  0.001  0.000
  Female sex                        -0.059  0.012  0.000
  (ln) Gestational age               2.365  0.146  0.000
  Parity                             0.035  0.013  0.008
  Fall delivery                     -0.040  0.020  0.046
  Winter delivery                    0.007  0.017  0.696
  Spring delivery                    0.026  0.019  0.184
  Delivery by cesarean section (a)          NA
NYC African American (n = 168)      Adjusted [R.sup.2] = 0.185
  (Constant)                         2.665  1.194  0.027
  (ln) [SIGMA]8 c-PAHs              -0.055  0.019  0.004
  Maternal height                    0.000  0.001  0.961
  Prepregnancy weight                0.001  0.001  0.105
  Female sex                        -0.042  0.024  0.086
  (ln) Gestational age               1.474  0.322  0.000
  Parity                             0.025  0.031  0.408
  Fall delivery                     -0.008  0.032  0.792
  Winter delivery                   -0.003  0.035  0.939
  Spring delivery                   -0.034  0.033  0.313
  Delivery by cesarean section (a)          NA
NYC Dominican (n = 212)             Adjusted [R.sup.2] = 0.282
  (Constant)                         0.610  0.913  0.505
  (ln) [SIGMA]8 c-PAHs               0.018  0.011  0.094
  Maternal height                    0.000  0.001  0.757
  Prepregnancy weight                0.001  0.001  0.022
  Female sex                        -0.023  0.016  0.147
  (ln) Gestational age               2.013  0.245  0.000
  Parity                             0.004  0.017  0.795
  Fall delivery                     -0.044  0.023  0.054
  Winter delivery                   -0.019  0.024  0.435
  Spring delivery                   -0.051  0.023  0.029
  Delivery by cesarean section (a)          NA

                                    (ln) Birth length
                                    [beta]  SE     p-Value

Krakow Caucasian (n = 340)          Adjusted [R.sup.2] = 0.369
  (Constant)                         1.148  0.224  0.000
  (ln) [SIGMA]8 c-PAHs              -0.009  0.003  0.003
  Maternal height                    0.001  0.000  0.014
  Prepregnancy weight                0.001  0.000  0.003
  Female sex                        -0.021  0.005  0.000
  (ln) Gestational age               0.721  0.058  0.000
  Parity                             0.005  0.005  0.307
  Fall delivery                     -0.019  0.008  0.018
  Winter delivery                   -0.004  0.007  0.597
  Spring delivery                    0.003  0.008  0.662
  Delivery by cesarean section (a)          NA
NYC African American (n = 168)      Adjusted [R.sup.2] = 0.197
  (Constant)                         1.584  0.369  0.000
  (ln) [SIGMA]8 c-PAHs              -0.011  0.007  0.112
  Maternal height                    0.000  0.000  0.795
  Prepregnancy weight                0.000  0.000  0.634
  Female sex                        -0.011  0.009  0.196
  (ln) Gestational age               0.632  0.100  0.000
  Parity                             0.016  0.011  0.159
  Fall delivery                      0.002  0.011  0.860
  Winter delivery                    0.002  0.013  0.849
  Spring delivery                   -0.005  0.012  0.665
  Delivery by cesarean section (a)          NA
NYC Dominican (n = 212)             Adjusted [R.sup.2] = 0.061
  (Constant)                         1.548  0.652  0.018
  (ln) [SIGMA]8 c-PAHs               0.003  0.008  0.712
  Maternal height                    0.000  0.001  0.573
  Prepregnancy weight                0.000  0.000  0.985
  Female sex                        -0.002  0.011  0.853
  (ln) Gestational age               0.629  0.176  0.000
  Parity                            -0.005  0.012  0.659
  Fall delivery                      0.000  0.016  0.980
  Winter delivery                    0.014  0.017  0.424
  Spring delivery                   -0.026  0.017  0.123
  Delivery by cesarean section (a)          NA

                                    (ln) Birth head circum
                                    [beta]  SE     p-Value

Krakow Caucasian (n = 340)          Adjusted [R.sup.2] = 0.288
  (Constant)                         1.707  0.193  0.000
  (ln) [SIGMA]8 c-PAHs              -0.006  0.002  0.010
  Maternal height                    0.001  0.000  0.017
  Prepregnancy weight                0.001  0.000  0.001
  Female sex                        -0.022  0.004  0.000
  (ln) Gestational age               0.445  0.050  0.000
  Parity                             0.015  0.004  0.001
  Fall delivery                     -0.008  0.007  0.222
  Winter delivery                    0.001  0.006  0.909
  Spring delivery                    0.009  0.006  0.173
  Delivery by cesarean section (a)   0.012  0.005  0.031
NYC African American (n = 168)      Adjusted [R.sup.2] = 0.232
  (Constant)                         1.352  0.369  0.000
  (ln) [SIGMA]8 c-PAHs              -0.010  0.007  0.125
  Maternal height                    0.000  0.000  0.571
  Prepregnancy weight                0.000  0.000  0.060
  Female sex                        -0.028  0.009  0.002
  (ln) Gestational age               0.578  0.100  0.000
  Parity                             0.005  0.011  0.634
  Fall delivery                     -0.014  0.011  0.221
  Winter delivery                   -0.004  0.013  0.737
  Spring delivery                   -0.008  0.012  0.536
  Delivery by cesarean section (a)   0.029  0.019  0.118
NYC Dominican (n = 212)             Adjusted [R.sup.2] = 0.255
  (Constant)                         1.599  0.282  0.000
  (ln) [SIGMA]8 c-PAHs               0.004  0.003  0.168
  Maternal height                    0.000  0.000  0.490
  Prepregnancy weight               -0.000  0.000  0.990
  Female sex                        -0.018  0.005  0.000
  (ln) Gestational age               0.518  0.076  0.000
  Parity                            -0.005  0.005  0.330
  Fall delivery                     -0.005  0.007  0.495
  Winter delivery                    0.014  0.007  0.062
  Spring delivery                   -0.005  0.007  0.511
  Delivery by cesarean section (a)   0.023  0.008  0.003

Abbreviations: circum, circumference; NA, not applicable.
(a) Cesarean section delivery method is not a risk factor for birth
weight or birth length.

Table 3. Risk of reduced birth outcomes, restricting the samples to
those within 1.80 - 36.47 ng/[m.sup.3] of PAH exposure range.

                        (ln) Birth weight       (ln) Birth length
                        [beta]  SE     p-Value  [beta]  SE     p-Value

Krakow Caucasian
  (Constant)            -1.174  0.758  0.123     0.929  0.303  0.002
  (ln) [SIGMA]8 c-PAHs  -0.021  0.013  0.091    -0.009  0.005  0.067
  Maternal height        0.004  0.002  0.015     0.002  0.001  0.002
  Prepregnancy weight    0.003  0.001  0.003     0.000  0.000  0.222
  Female sex            -0.056  0.016  0.001    -0.020  0.006  0.002
  (ln) Gestational age   2.338  0.197  0.000     0.750  0.079  0.000
  Parity                 0.045  0.016  0.006     0.011  0.007  0.103
  Fall delivery         -0.040  0.022  0.070    -0.018  0.009  0.038
  Winter delivery        0.020  0.021  0.334     0.004  0.008  0.633
  Spring delivery       -0.022  0.033  0.502    -0.013  0.013  0.331
  Delivery by cesarean          NA                      NA
    section
NYC African American
  (Constant)             2.348  1.360  0.087     1.785  0.426  0.000
  (ln) [SIGMA]8 c-PAHs  -0.085  0.028  0.003    -0.008  0.009  0.341
  Maternal height       -0.002  0.002  0.289     0.000  0.000  0.323
  Prepregnancy weight    0.001  0.001  0.276     0.000  0.000  0.378
  Female sex            -0.064  0.030  0.034    -0.010  0.009  0.285
  (ln) Gestational age   1.650  0.370  0.000     0.598  0.116  0.000
  Parity                 0.022  0.039  0.574     0.013  0.012  0.278
  Fall delivery          0.042  0.041  0.315     0.020  0.013  0.125
  Winter delivery        0.007  0.040  0.861     0.009  0.013  0.496
  Spring delivery       -0.004  0.039  0.923     0.011  0.012  0.359
  Delivery by cesarean          NA                      NA
    section
NYC Dominican
  (Constant)             1.772  1.150  0.125     1.376  0.879  0.119
  (ln) [SIGMA]8 c-PAHs   0.006  0.017  0.709     0.011  0.013  0.404
  Maternal height        0.000  0.001  0.874     0.001  0.001  0.448
  Prepregnancy weight    0.002  0.001  0.024     0.000  0.001  0.977
  Female sex            -0.014  0.019  0.456     0.007  0.014  0.631
  (ln) Gestational age   1.701  0.308  0.000     0.658  0.236  0.006
  Parity                 0.004  0.021  0.833    -0.006  0.015  0.675
  Fall delivery         -0.054  0.029  0.064    -0.005  0.022  0.805
  Winter delivery       -0.010  0.029  0.719     0.018  0.022  0.410
  Spring delivery       -0.062  0.028  0.027    -0.025  0.021  0.229
  Delivery by cesarean          NA                      NA
    section

                        (ln) Birth head circum
                        [beta]  SE     p-Value

Krakow Caucasian
  (Constant)             1.636  0.259  0.000
  (ln) [SIGMA]8 c-PAHs  -0.008  0.004  0.059
  Maternal height        0.001  0.001  0.023
  Prepregnancy weight    0.001  0.000  0.094
  Female sex            -0.018  0.005  0.001
  (ln) Gestational age   0.459  0.067  0.000
  Parity                 0.020  0.005  0.000
  Fall delivery         -0.011  0.007  0.126
  Winter delivery       -0.001  0.007  0.941
  Spring delivery       -0.005  0.011  0.682
  Delivery by cesarean   0.015  0.007  0.031
    section
NYC African American
  (Constant)             1.603  0.515  0.002
  (ln) [SIGMA]8 c-PAHs  -0.023  0.011  0.029
  Maternal height        0.000  0.001  0.664
  Prepregnancy weight    0.000  0.000  0.215
  Female sex            -0.042  0.012  0.000
  (ln) Gestational age   0.541  0.140  0.000
  Parity                 0.005  0.016  0.739
  Fall delivery         -0.008  0.016  0.631
  Winter delivery       -0.001  0.016  0.929
  Spring delivery       -0.005  0.015  0.722
  Delivery by cesarean   0.043  0.023  0.061
    section
NYC Dominican
  (Constant)             1.926  0.332  0.000
  (ln) [SIGMA]8 c-PAHs   0.005  0.005  0.289
  Maternal height        0.000  0.000  0.941
  Prepregnancy weight    0.000  0.000  0.287
  Female sex            -0.016  0.005  0.002
  (ln) Gestational age   0.434  0.089  0.000
  Parity                -0.006  0.006  0.329
  Fall delivery         -0.004  0.008  0.614
  Winter delivery        0.012  0.008  0.142
  Spring delivery       -0.009  0.008  0.244
  Delivery by cesarean   0.019  0.008  0.024
    section

Abbreviations: circum, circumference; NA, not applicable.
COPYRIGHT 2006 National Institute of Environmental Health Sciences
No portion of this article can be reproduced without the express written permission from the copyright holder.
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Title Annotation:Children's Health
Author:Perera, Frederica P.
Publication:Environmental Health Perspectives
Date:Nov 1, 2006
Words:9844
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Brain delay: air pollutants linked to slow childhood mental development.
Air today, trouble tomorrow.
Urinary 1-hydroxypyrene as a biomarker of PAH exposure in 3-year-old Ukrainian children.
PAHs and cognitive impairment: prenatal exposure catches up with toddlers.
Effect of prenatal exposure to airborne polycyclic aromatic hydrocarbons on neurodevelopment in the first 3 years of life among inner-city children.
PAH-DNA adducts in cord blood and fetal and child development in a Chinese cohort.

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