Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity.

BACKGROUND/OBJECTIVES: Cesarean section (CS) and antibiotic use during pregnancy may alter normal maternal-offspring microbiota exchange, thereby contributing to aberrant microbial colonization of the infant gut and increased susceptibility to obesity later in life. We hypothesized that (i) maternal use of antibiotics in the second or third trimester of pregnancy and (ii) CS are independently associated with higher risk of childhood obesity in the offspring. SUBJECTS/METHODS: Of the 727 mothers enrolled in the Northern Manhattan Mothers and Children Study, we analyzed the 436 mother-child dyads followed until 7 years of age with complete data. We ascertained prenatal antibiotic use by a questionnaire administered late in the third trimester, and delivery mode by medical record. We derived age- and sex-specific body mass index (BMI) z-scores using the CDC SAS Macro, and defined obesity as BMI z⩾95th percentile. We used binary regression with robust variance and linear regression models adjusted for maternal age, ethnicity, pre-gravid BMI, maternal receipt of public assistance, birth weight, sex, breastfeeding in the first year and gestational antibiotics or delivery mode. RESULTS: Compared with children not exposed to antibiotics during the second or third trimester, those exposed had 84% (33-154%) higher risk of obesity, after multivariable adjustment. Second or third trimester antibiotic exposure was also positively associated with BMI z-scores, waist circumference and % body fat (all P<0.05). Independent of prenatal antibiotic usage, CS was associated with 46% (8-98%) higher offspring risk of childhood obesity. Associations were similar for elective and non-elective CS. CONCLUSIONS: In our cohort, CS and exposure to antibiotics in the second or third trimester were associated with higher offspring risk of childhood obesity. Future studies that address the limitations of our study are warranted to determine if prenatal antibiotic use is associated with offspring obesity. Research is also needed to determine if alterations in neonatal gut microbiota underlie the observed associations.

A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures.

Inner-city minority populations are high-risk groups for adverse birth outcomes and also more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), benzo[a]pyrene B[a]P, other ambient polycyclic aromatic hydrocarbons (global PAHs), and residential pesticides. The Columbia Center for Children's Environmental Health (CCCEH) is conducting a prospective cohort study of 700 northern Manhattan pregnant women and newborns to examine the effects of prenatal exposure to these common toxicants on fetal growth, early neurodevelopment, and respiratory health. This paper summarizes results of three published studies demonstrating the effects of prenatal ETS, PAH, and pesticides on birth outcomes and/or neurocognitive development [Perera FP, Rauh V, Whyatt RM, Tsai WY, Bernert JT, Tu YH, et al. Molecular evidence of an interaction between prenatal environment exposures on birth outcomes in a multiethnic population. Environ Health Perspect 2004;12:630-62; Rauh VA, Whyatt RM, Garfinkel R, Andrews H, Hoepner L, Reyes A, et al. Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children. Neurotoxicol Teratol 2004;26:373-85; Whyatt RM, Rauh V, Barr DB, Camann DE, Andrews HF, Garfinkel R, et al. Prenatal insecticide exposures, birth weight and length among an urban minority cohort. Environ Health Perspect, in press]. To evaluate the effects of prenatal exposure to ETS, PAHs, and pesticides, researchers analyzed questionnaire data, cord blood plasma (including biomarkers of ETS and pesticide exposure), and B[a]P-DNA adducts (a molecular dosimeter of PAHs). Self-reported ETS was associated with decreased head circumference (P = 0.04), and there was a significant interaction between ETS and adducts such that combined exposure had a significant multiplicative effect on birth weight (P = 0.04) and head circumference (P = 0.01) after adjusting for confounders. A second analysis examined the neurotoxic effects of prenatal ETS exposure and postpartum material hardship (unmet basic needs in the areas of food, housing, and clothing) on 2-year cognitive development. Both exposures depressed cognitive development (P < 0.05), and there was a significant interaction such that children with exposure to both ETS and material hardship exhibited the greatest cognitive deficit (7.1 points). A third analysis found that cord chlorpyrifos, and a combined measure of cord chlorpyrifos, diazinon, and propoxur-metabolite, were inversely associated with birth weight and/or length (P < 0.05). These results underscore the importance of policies that reduce exposure to ETS, air pollution, and pesticides with potentially adverse effects on fetal growth and child neurodevelopment.

Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA.

The postulated importance of oxidative damage to DNA in aging and age-related degenerative pathologies such as cancer has prompted efforts to develop sensitive quantitation methods. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is a widely used marker for oxidative damage to DNA. To develop an immunoassay for quantitation of 8-OHdG, two monoclonal antibodies have been developed and characterized by competitive enzyme-linked immunosorbent assay (ELISA). Antibody 1F7 has 50% inhibition at 5 pmol 8-OHdG and 1 x 10(5) pmol dG, while antibody 1F11 has 50% inhibition at 2.5 pmol 8-OHdG and 2000 pmol dG. Both antisera crossreact with guanosine and several structurally related derivatives, including 6- and 8-mercaptoguanosine, 8-bromoguanosine, 8-methylguanine, and 7-methylguanosine. Immunoaffinity columns were prepared with antibody 1F7, which exhibits higher selectivity than 1F11, to isolate 8-OHdG from DNA hydrolyzates followed by ELISA quantitation with antibody 1F11. This method allows the analysis of approximately one 8-OHdG/10(5) dG using 100 micrograms DNA. To validate the assay, DNA extracted from human placental tissues were assayed by both ELISA and HPLC with electrochemical detection. Values by both methods correlated well (r = 0.87, p < 0.001), but the levels determined by ELISA were approximately sixfold higher than those determined by HPLC. This may be due to oligonucleotides detected by the ELISA but not the HPLC method or crossreactivity with other damaged bases present in the immunoaffinity purified material. Placental samples from current smokers had significantly higher 8-OHdG by ELISA than those from nonsmokers (p < 0.05). The method of immunoaffinity purification combined with ELISA quantitation has sufficient sensitivity for detecting 8-OHdG in human DNA samples. Although absolute values are higher than those determined by HPLC, the method provides a good alternative to the HPLC-EC method for monitoring relative oxidative damage in molecular epidemiological studies.

Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants; a number are carcinogenic. Metabolic polymorphisms may modulate susceptibility to PAH-induced DNA damage and carcinogenesis. This study investigates the relationship between PAH-DNA adduct levels (in maternal and newborn WBCs) and two polymorphisms: (a) an MspI RFLP in the 3' noncoding region of cytochrome P4501A1 (CYP1A1); and (b) an A-->G transition in nucleotide 313 of glutathione S-transferase P1 (GSTP1), resulting in an ile105val substitution. CYP1A1 catalyzes the bioactivation of PAH; the CYP1A1 MspI RFLP has been associated with cancer of the lung. GSTP1 catalyzes the detoxification of PAH; the val allele has greater catalytic efficiency toward PAH diol epoxides. The study involves 160 mothers and their newborns from Poland. Regression models controlled for maternal smoking and other confounders. No association was seen between maternal adduct levels and either polymorphism, separately or combined. However, adduct levels were higher among newborns with the CYP1A1 MspI restriction site (heterozygotes and homozygotes combined) compared with newborns lacking the restriction site (P = 0.06). Adducts were higher among GSTP1 ile/val and ile/ile newborns compared with GSTP1 val/val newborns (P = 0.08). Adduct levels were 4-fold higher among GSTP1 ile/ile newborns having the CYP1A1 restriction site compared with GSTP1 val/val newborns who lacked the CYP1A1 restriction site (P = 0.04). This study demonstrates a significant combined effect of phase I and phase II polymorphisms on DNA damage from PAHs in fetal tissues. It illustrates the importance of considering interindividual variation in assessing risks of transplacental exposure to PAHs.

Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells and urinary 1-hydroxypyrene in foundry workers.

In an ongoing comprehensive evaluation of biological markers, workers in or near an iron foundry with varying exposure to polycyclic aromatic hydrocarbons (PAH) were analyzed for molecular response to this exposure. Exposure to benzo(a)pyrene, determined by personal monitors worn by the workers (2 to 60 ng/m3), was considerably lower than in a previous study at this foundry (< 50 to 200 ng/m3) (F.P. Perera et al., Cancer Res., 48: 2288-2291, 1988). Two biomarkers, 1-hydroxypyrene in urine measured by high-performance liquid chromatography with fluorescence detection (a measure of internal dose) and PAH-DNA adducts in WBC measured by immunoassay (a measure of biologically effective dose) were assessed to demonstrate their relationship to the lowest exposures yet analyzed in foundry workers. In addition, these markers were analyzed for dose response and interindividual variability. Cigarette smoking, but not age or charbroiled food, influenced the level of 1-hydroxypyrene but not PAH-DNA adducts. When workers were classified into three exposure categories (low, medium, and high), mean 1-hydroxypyrene levels were 2.7, 1.8, and 3.6 mumol/mol creatinine, respectively. Comparisons by analysis of variance showed a significant difference between the groups after controlling for smoking (P = 0.02), but a trend test using multivariate linear regression analysis was not significant (r = 0.27; P = 0.07). Substantial interindividual variation was demonstrated by the 19- to 20-fold range in the values within each of the three exposure groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinogen-DNA adducts in human breast tissue.

Breast cancer is the second leading cause of cancer death among American women. Known risk factors account for only approximately one-third of the 182,000 new cases diagnosed each year in the United States. There is both concern and debate over the contribution of environmental exposures related to lifestyle, occupation, and ambient pollution, particularly in high risk areas such as Long Island, NY and the rest of the northeastern United States. Biomarkers such as carcinogen-DNA adducts can help to explore the role of environmental risk factors for breast cancer by documenting DNA damage from specific carcinogens directly in human tissue. In this pilot study, a total of 31 breast tissue samples were analyzed by the 32P-postlabeling method for carcinogen-DNA adducts characteristic of complex mixtures of aromatic compounds (such as polycyclic aromatic hydrocarbons) and tobacco smoke. The samples included tumor and tumor-adjacent tissues from 15 women with breast cancer and normal tissue samples from 4 women undergoing breast reduction. Among the breast cancer cases, the mean aromatic/hydrophobic-DNA adduct level in all tissues assayed was 5.3 +/- 2.4 (SD) adducts/10(8) nucleotides compared to 2.3 +/- 1.5 among the samples from the noncancer patients. Breast tissue (tumor and/or nontumor) from 30% (5 of 15) of women with breast cancer displayed a pattern of adducts (referred to as a diagonal zone of radioactivity) associated previously, in studies of other tissues, with exposure to tobacco smoke. The 5 positive samples were from current smokers; tissue samples from the 8 nonsmoking cases did not show this characteristic pattern (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

CYP1A1 messenger RNA levels in placental tissue as a biomarker of environmental exposure.

The human CYP1A1 gene codes for an inducible enzyme system involved in biotransformation of certain xenobiotics, including polycyclic aromatic hydrocarbons; some of the metabolites are carcinogenic and mutagenic. Effects of environmental exposures (smoking, air pollution, and diet) on CYP1A1 gene induction in placental tissue and the modulation of induction by the CYP1A1 MspI RFLP were evaluated in two groups from Poland: 70 mother-child pairs from Krakow, a city with elevated air pollution; and 90 pairs from Limanowa, a less polluted area. Compared to placentas from nonsmoking women, CYP1A1 mRNA levels were significantly increased in placentas from current smokers (P < 0.001). Ex-smokers also had significantly higher placental mRNA levels, including women who quit smoking prior to pregnancy (P < 0.01). A marginal increase in CYP1A1 mRNA with environmental tobacco smoke exposure was evident. Within Krakow, there was an increase in CYP1A1 mRNA with ambient pollution at the place of residence for each woman, which was significant among women who were not employed away from the home (P < 0.05 controlling for smoking status, diet, and use of coal for heating). Significant increases in mRNA were associated with dietary consumption of smoked meat, cheese, and fish (P < 0.01). The CYP1A1 MspI RFLP was not a significant determinant of CYP1A1 mRNA levels after controlling for smoking and other variables. Human placenta provides a readily available and responsive system that can serve as a model for evaluating environmental and genetic determinants of CYP1A1 induction.

Biomarkers of polycyclic aromatic hydrocarbon-DNA damage and cigarette smoke exposures in paired maternal and newborn blood samples as a measure of differential susceptibility.

Human and experimental evidence indicates that the developing fetus may be more susceptible than the adult to the effects of certain carcinogens, including some polycyclic aromatic hydrocarbons (PAHs). Factors that can modulate susceptibility include proliferation rates, detoxification capabilities, and DNA repair capacity. Biomarkers can facilitate quantification of age-related susceptibility among human populations. In this study, we report on three biomarkers measured in paired blood samples collected at birth from 160 Polish mothers and newborns: 70 pairs from Krakow (a city with high air pollution including PAHs) and 90 pairs from Limanowa (an area with lower ambient pollution but greater indoor coal use). Biomarkers were: WBC aromatic-DNA adducts by (32)P-postlabeling and PAH-DNA adducts by ELISA (as indicators of DNA damage from PAHs and other aromatics) and plasma cotinine (as an internal dosimeter of cigarette smoke). Correlations were assessed by Spearman's rank test, and differences in biomarker levels were assessed by the Wilcoxon signed-ranks test. A significant correlation between paired newborn/maternal samples was seen for aromatic-DNA adduct levels (r = 0.3; P < 0.001) and plasma cotinine (r = 0.8; P < 0.001) but not PAH-DNA adduct levels (r = 0.14; P = 0.13). Among the total cohort, levels of the three biomarkers were higher in newborn samples compared with paired maternal samples. The difference was significant for aromatic-DNA adduct levels (16.6 +/- 12.5 versus 14.21 +/- 15.4/10(8) nucleotides; P = 0.002) and plasma cotinine (14.2 +/- 35.5 versus 8.3 +/- 24.5 ng/ml; P < 0.001) but not for PAH-DNA adduct levels (7.9 +/- 9.9 versus 5.9 +/- 8.2/10(8) nucleotides; P = 0.13). When analyses were restricted to the 80 mother/newborn pairs from whom the blood sample was drawn concurrently (within 1 h of each other), levels of all of the three biomarkers were significantly higher in the newborn compared with paired maternal blood samples (P < 0.05). Results suggest reduced detoxification capabilities and increased susceptibility of the fetus to DNA damage, especially in light of experimental evidence that transplacental exposures to PAHs are 10-fold lower than paired maternal exposures. The results have implications for risk assessment, which currently does not adequately account for sensitive subsets of the population.

Application of biologic markers to studies of environmental risks in children and the developing fetus.

Young children and the developing fetus may be more susceptible to effects of environmental toxicants than adults due to differential exposure patterns and developmental immaturities. Biologic markers offer the potential of quantitative dosimeters of biologic dose and/or indices of biologic effect associated with fetal/childhood exposures. They can facilitate evaluation of interindividual variability in response and the magnitude of age-related susceptibilities. Thus far, biologic markers have not been widely used in developmental epidemiology of environmental exposures. Research by our group and others has seen elevations in biologic markers in samples from children and fetal tissue associated with a spectrum of environmental exposures, including tobacco smoke (active and passive), ambient pollution, and dietary contaminants. Studies also suggest that biologic markers can provide powerful dosimeters for investigating reproductive effects. Validation of biologic markers offering the greatest promise for developmental epidemiology is needed.

Measurement of organophosphate metabolites in postpartum meconium as a potential biomarker of prenatal exposure: a validation study.

Experimental data have linked exposure to prenatal organophosphates to adverse neurocognitive sequalae. However, epidemiologic research has been hampered by lack of reliable dosimeters. Existing biomarkers reflect short-term exposure only. Measurements of pesticides in postpartum meconium may yield a longer-term dosimeter of prenatal exposure. As the initial step in biomarker validation, this research determined background levels, detection limits, and stabilities of six organophosphate metabolites in meconium: diethylphosphate (DEP), diethylthiophosphate (DETP), diethyldithiophosphate (DEDTP), dimethylphosphate (DMP), dimethylthiophosphate (DMTP), and dimethyldithiophosphate (DMDTP). Calibration curves were also constructed. The meconium was collected from 20 newborns at New York Presbyterian Hospital; analyses were undertaken at the Centers for Disease Control and Prevention (CDC). DEP was detected in 19/20 samples (range 0.8-3.2 microg/g) and DETP was detected in 20/20 (range 2.0-5.6 microg/g). DMP and DEDTP were each detected in 1/20 (at 16 and 1.8 microg/g, respectively). DMTP and DMDTP were not detected. Detection limits were comparable to or lower than those in urine; levels were similar to those seen in adult urine in population-based research. Metabolites were stable at room temperature over 12 hr. Calibration curves were linear over the range tested (0.5-400 microg/g); recoveries ranged from 18% to 66%. Using isotope dilution, recoveries of each analyte in individual samples can be corrected automatically based on the recovery of the respective stable isotope-labeled analogue, making this method fully quantitative. Results indicate that measurements of organophosphate metabolites in meconium have promise as biomarkers of prenatal exposure. Further research is needed to determine the time frame of exposure represented by pesticide levels in meconium and to evaluate the dose-response relationship.

Molecular epidemiologic research on the effects of environmental pollutants on the fetus.

Evidence shows that fetuses and infants are more affected than adults by a variety of environmental toxicants because of differential exposure, physiologic immaturity, and a longer lifetime over which disease initiated in early life can develop. In this article we review data on the effects of in utero exposure to common environmental contaminants, including polycyclic aromatic hydrocarbons (PAH), particulate matter and environmental tobacco smoke (ETS). We then summarize results from our molecular epidemiologic study to assess risks from in utero exposures to ambient air pollution and ETS. This research study, conducted in Poland, used biomarkers to measure the internal and bioeffective dose of toxicants and individual susceptibility factors. The study included 160 mothers and 160 newborns. Ambient air pollution was significantly associated (p= 0.05) with the amount of PAH bound to DNA (PAH-DNA adducts) in both maternal and infant cord white blood cells (WBC). Newborns with elevated PAH-DNA adducts (greater than the median) had significantly decreased birth weight (p= 0.05), birth length (p= 0.02), and head circumference (p= 0.0005) compared to the newborns with lower adducts (n= 135). Maternal and infant cotinine levels were increased by active and passive cigarette smoke exposure of the mother (p= 0.01). An inverse correlation was seen between newborn plasma cotinine (nanograms per milliliter) and birth weight (p= 0.0001) and length (p= 0.003). Adducts were elevated in placental tissue and WBC of newborns who were heterozygous or homozygous for the cytochrome P4501A1 MspI restriction fragment length polymorphism (RFLP) compared to newborns without the RFLP. Levels of PAH-DNA and cotinine were higher in newborns than mothers. These results document that there is significant transplacental transfer of PAH and ETS constituents from mother to fetus; that PAH-DNA adduct levels in maternal and newborn WBC were increased with environmental exposure to PAH from ambient pollution; and that the fetus is more sensitive to genetic damage than the mother. The study also provided the first molecular evidence that transplacental PAH exposure to the fetus is compromising fetal development. If confirmed, these findings could have significant public health implications since a number of studies have found that reduction of head circumference at birth correlates with lower intelligence quotient as well as poorer cognitive functioning and school performance in childhood.

Workshop to identify critical windows of exposure for children's health: cancer work group summary.

We considered whether there are discrete windows of vulnerability in the development of cancer and which time periods may be of the greatest importance. Cancer was considered broadly, including cancers in childhood as well as adult cancers that may have an in utero or childhood origin. We concluded that there was evidence from animal and epidemiologic studies for causal relationships for preconceptional, in utero, and childhood exposures and cancer occurrence in children and adults. However, the evidence is incomplete and all relevant critical windows may not have been identified. The comprehensive evaluation of the relative importance of specific time windows of exposure is limited. Improvements in the design of epidemiologic studies and additional animal studies of mechanisms are warranted.

Molecular epidemiology in environmental carcinogenesis.

Molecular epidemiology has significant potential in preventing cancer and other diseases caused by environmental exposures (related to lifestyle, occupation, or ambient pollution). This approach attempts to prevent cancer by incorporating laboratory methods to document the molecular dose and preclinical effects of carcinogens, as well as factors that increases individual susceptibility to carcinogens. Recently we have carried out validation studies of biologic markers such as carcinogen--DNA and carcinogen--protein adducts, gene and chromosomal mutations, alterations in target oncogenes or tumor suppressor genes, polymorphisms in putative susceptibility genes (individual P450s, glutathione transferase M1), and serum levels of micronutrients. This research involves adults, infants, and children exposed to varying levels of carcinogens, as well as cancer cases and controls. On a group level, dose-response relationships have frequently been seen between various biomarkers and environmental exposures such as polycyclic aromatic hydrocarbons, cigarette smoke (active and passive), and ambient indoor and workplace air pollution. However, there is significant interindividual variation in biomarkers that appears to reflect a modulating effect on biomarkers (hence potential risk) by genetic and acquired susceptibility factors. Ongoing retrospective and nested case-control studies of lung and breast cancer are examining the association between biomarkers and cancer risk. Results of these studies are encouraging; they suggest that biomarkers, once validated, can be useful in identifying populations and individuals at risk in time to intervene effectively.

Relationship between ambient air pollution and DNA damage in Polish mothers and newborns.

Industrialized regions in Poland are characterized by high ambient pollution, including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry and home heating. In experimental bioassays, certain PAHs are transplacental carcinogens and developmental toxicants. Biologic markers can facilitate evaluation of effects of environmental PAHs on the developing infant. We measured the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland, an industrialized city with elevated air pollution. Modulation of adduct levels by genotypes previously linked to risk of lung cancer, specifically glutathione S-transferase MI (GSTM1) and cytochrome P4501A1 (CYP1A1) Msp restriction fragment length polymorphism (RFLP), was also investigated. There was a dose-related increase in maternal and newborn adduct levels with ambient pollution at the women's place of residence among subjects who were not employed away from home (p < or = 0.05). Maternal smoking (active and passive) significantly increased maternal (p < or = 0.01) but not newborn adduct levels. Neither CYP1A1 Msp nor GSTM1 polymorphisms was associated with maternal adducts. However, adducts were significantly higher in newborns heterozygous or homozygous for the CYP1A1 Msp RFLP compared to newborns without the RFLP (p = 0.04). Results indicate that PAH-induced DNA damage in mothers and newborns is increased by ambient air pollution. In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism.

Exposure misclassification error in studies on prenatal effects of tobacco smoking in pregnancy and the birth weight of children.

Adverse effects of maternal smoking have been mostly identified through epidemiologic investigations that have used questionnaires to assess active and passive smoking. However, unvalidated self-reports of cigarette smoking may bias true estimates of relative risk of smoking-related health outcomes. This report is based on two separate investigations. First, within a molecular epidemiologic study of the relationship between environmental exposures (smoking, air pollution, diet) and developmental impairment, we have compared self-reported tobacco smoke exposure during pregnancy to plasma cotinine measurements in mothers. One hundred and fifty-eight patients from obstetrical wards in Cracow and in Limanowa, Poland were included in the parent study. Biochemically-identified smokers were defined as persons with plasma cotinine levels greater than 25 ng/mL. The data showed that exposure classification based on self-reported smoking status compared with cotinine values was of low sensitivity (52%) but of high specificity (98%). We assessed the effect of this exposure classification error on the association between low birth weight (LBW) and smoking in pregnancy using data from a related epidemiologic study of children's health in Cracow involving 1115 subjects. The odds ratio (OR) estimates for smoking and LBW after adjustment for exposure misclassification error were significantly higher than before adjustment (crude OR = 2.9, corrected OR = 5.1). The estimated attributable fraction (AF(pop)) based on the crude OR amounted to 22%; however, after adjustment it reached 50%. The corresponding values for the attributable fraction in the exposed group (AF(exp)) were 66% and 80%. These results illustrate the value of validating questionnaire responses on smoking during pregnancy against reliable biologic markers.

Developmental effects of exposure to environmental tobacco smoke and material hardship among inner-city children.

Because of the growing concern that exposures to airborne pollutants have adverse effects on fetal growth and early childhood neurodevelopment, and the knowledge that such exposures are more prevalent in disadvantaged populations, we assessed the joint impact of prenatal exposure to environmental tobacco smoke (ETS) and material hardship on the 2-year cognitive development of inner-city children, adjusted for other sociodemographic risks and chemical exposures. The purpose was to evaluate the neurotoxicant effects of ETS among children experiencing different degrees of socioeconomic disadvantage, within a minority population. The sample did not include children exposed to active maternal smoking in the prenatal period. Results showed significant adverse effects of prenatal residential ETS exposure and the level of material hardship on 2-year cognitive development, as well as a significant interaction between material hardship and ETS, such that children with both ETS exposure and material hardship exhibited the greatest cognitive deficit. In addition, children with prenatal ETS exposure were twice as likely to be classified as significantly delayed, as compared with nonexposed children. Postnatal ETS exposure in the first 2 years of life did not contribute independently to the risk of developmental delay, over and above the risk posed by prenatal ETS exposure. The study concluded that prenatal exposure to ETS in the home has a negative impact on 2-year cognitive development, and this effect is exacerbated under conditions of material hardship in this urban minority sample.

[Classification exposure error in studies on tobacco smoke in pregnancy and birth weight of newborns]. / Blad klasyfikacyjny ekspozycji w badaniach wplywu palenia tytoniu przez kobiety w ciazy na mase urodzeniowa noworodka.

The purpose of the paper was to assess the validity of the self-reported tobacco smoke exposure in pregnancy against plasma cotinine measurements. A total of 158 patients from obstetrical wards was included in the cotinine study. Biochemical smokers were defined as persons with serum cotinine levels greater than 25 ng/ml. The data showed that the exposure classification based on self-reported smoking habit status confronted with cotinine values was of low sensitivity (52%) but of high specificity (98%). To assess the effect of this exposure classification error on the association between the low birth weight (LBW) and smoking in pregnancy, the data from the recent survey in Cracow children have been used. It was shown that RR estimates for smoking and LBW after adjustment for misclassification error were substantially higher than that not adjusted (crude RR = 2.9, corrected RR = 5.1). Due to the exposure misclassification error the attributable fraction (AF) of LBW due to mother's smoking was heavily biased as well. Estimated attributable fraction AF(pop) based on crude RR amounted to 22%, however, after adjustment reached 50%. The corresponding values for attributable fraction in exposed group AF(exp) were 66% and 80%.

A review of alternatives to di (2-ethylhexyl) phthalate-containing medical devices in the neonatal intensive care unit.

OBJECTIVE: To conduct an extensive literature and toxicological database review on substitute compounds and available alternative medical products to replace polyvinyl chloride (PVC) and/or di(2-ethylhexyl) phthalate (DEHP), and conduct a DEHP-medical inventory analysis at a large metropolitan neonatal intensive care unit (NICU). STUDY DESIGN: A systematic search for DEHP-free alternative products was performed using online databases. An informal audit of a large metropolitan NICU was undertaken in 2005 and 2006; 21 products were identified that could potentially contain DEHP. Availability of DEHP-free alternatives was determined through company websites and phone interviews. RESULT: Two alternative approaches are available for replacing DEHP in NICU medical products: (1) replacement by DEHP-free plasticizers; and (2) replacement of PVC entirely through the use of other polymers. Both approaches seem to provide less harmful substitutes to DEHP, but support PVC-free polymers as the preferred alternative. However, significant data gaps exist, particularly for the alternative polymers. In all, 10 out of 21 (48%) products in the NICU audit were DEHP-free; six consisted of alternative polymers and four of alternative plasticizers. Of the remaining 11 products, only three were available without DEHP at the time of the audit. CONCLUSION: Because of significant data gaps, systematic toxicological testing of DEHP-free alternatives is imperative. Continued development of alternative products is also needed.