Prenatal phenol and phthalate exposures and birth outcomes.

BACKGROUND: Many phthalates and phenols are hormonally active and are suspected to alter the course of development. OBJECTIVE: We investigated prenatal exposures to phthalate and phenol metabolites and their associations with body size measures of the infants at birth. METHODS: We measured 5 phenol and 10 phthalate urinary metabolites in a multiethnic cohort of 404 women in New York City during their third trimester of pregnancy and recorded size of infants at birth. RESULTS: Median urinary concentrations were > 10 microg/L for 2 of 5 phenols and 6 of 10 phthalate monoester metabolites. Concentrations of low-molecular-weight phthalate monoesters (low-MWP) were approximately 5-fold greater than those of high-molecular-weight metabolites. Low-MWP metabolites had a positive association with gestational age [0.97 day gestational age per ln-biomarker; 95% confidence interval (CI), 0.07-1.9 days, multivariate adjusted] and with head circumference. Higher prenatal exposures to 2,5-dichlorophenol (2,5-DCP) predicted lower birth weight in boys (-210 g average birth weight difference between the third tertile and first tertile of 2,5-DCP; 95% CI, 71-348 g). Higher maternal benzophenone-3 (BP3) concentrations were associated with a similar decrease in birth weight among girls but with greater birth weight in boys. CONCLUSIONS: We observed a range of phthalate and phenol exposures during pregnancy in our population, but few were associated with birth size. The association of 2,5-DCP and BP3 with reduced or increased birth weight could be important in very early or small-size births. In addition, positive associations of urinary metabolites with some outcomes may be attributable partly to unresolved confounding with maternal anthropometric factors.

Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy.

CONTEXT: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. OBJECTIVE: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. DESIGN: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. RESULTS: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. CONCLUSIONS: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.

Methodologic and logistic issues in conducting longitudinal birth cohort studies: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research.

In anticipation of the National Children's Study, lessons can be learned from the smaller birth cohort studies conducted by five Centers for Children's Environmental Health and Disease Prevention Research funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. The populations studied are diverse in ethnicity and social class and reside in urban and rural environments. Although almost all of the centers chose to enroll participants through medical care facilities, they had to develop independent staffs and structures because of the overburdened medical care system. Some of the lessons learned by the centers include the importance of continuous funding, building community partnerships to conduct culturally appropriate research, hiring bilingual and bicultural staff from the community, prioritizing research goals, developing biorepositories to ensure future utility of samples, instituting quality control procedures for all aspects of specimen and data collection, maintaining frequent contact with study participants, ensuring ethical conduct of the research in a changing medical-legal climate, and communicating results in a timely and appropriate manner to participants and the wider community. All centers underestimated the necessary start-up time, staff, and costs in conducting these birth cohort studies. Despite the logistical complexity and added expenses, all centers emphasize the importance of studying the impact of environmental exposures on those children most at risk, those living in minority and low-income communities. These centers present barriers encountered, solutions found, and considerations for future research, with the hope that the lessons learned can help inform the planning and conduct of the National Children's Study.

Exposures among pregnant women near the World Trade Center site on 11 September 2001.

We have characterized environmental exposures among 187 women who were pregnant, were at or near the World Trade Center (WTC) on or soon after 11 September 2001, and are enrolled in a prospective cohort study of health effects. Exposures were assessed by estimating time spent in five zones around the WTC and by developing an exposure index (EI) based on plume reconstruction modeling. The daily reconstructed dust levels were correlated with levels of particulate matter < or = 2.5 microm in aerodynamic diameter (PM2.5; r = 0.68) or PM10 (r = 0.73-0.93) reported from 26 September through 8 October 2001 at four of six sites near the WTC whose data we examined. Biomarkers were measured in a subset. Most (71%) of these women were located within eight blocks of the WTC at 0900 hr on 11 September, and 12 women were in one of the two WTC towers. Daily EIs were determined to be highest immediately after 11 September and became much lower but remained highly variable over the next 4 weeks. The weekly summary EI was associated strongly with women's perception of air quality from week 2 to week 4 after the collapse (p < 0.0001). The highest levels of polycyclic aromatic hydrocarbon-deoxyribonucleic acid (PAH-DNA) adducts were seen among women whose blood was collected sooner after 11 September, but levels showed no significant associations with EI or other potential WTC exposure sources. Lead and cobalt in urine were weakly correlated with sigmaEI, but not among samples collected closest to 11 September. Plasma OC levels were low. The median polychlorinated biphenyl level (sum of congeners 118, 138, 153, 180) was 84 ng/g lipid and had a nonsignificant positive association with sigmaEI (p > 0.05). 1,2,3,4,6,7,8-Heptachlorodibenzodioxin levels (median, 30 pg/g lipid) were similar to levels reported in WTC-exposed firefighters but were not associated with EI. This report indicates intense bystander exposure after the WTC collapse and provides information about nonoccupational exposures among a vulnerable population of pregnant women.

Study design: evaluating gene-environment interactions in the etiology of breast cancer - the WECARE study.

INTRODUCTION: Deficiencies in cellular responses to DNA damage can predispose to cancer. Ionizing radiation can cause cluster damage and double-strand breaks (DSBs) that pose problems for cellular repair processes. Three genes (ATM, BRCA1, and BRCA2) encode products that are essential for the normal cellular response to DSBs, but predispose to breast cancer when mutated. DESIGN: To examine the joint roles of radiation exposure and genetic susceptibility in the etiology of breast cancer, we designed a case-control study nested within five population-based cancer registries. We hypothesized that a woman carrying a mutant allele in one of these genes is more susceptible to radiation-induced breast cancer than is a non-carrier. In our study, 700 women with asynchronous bilateral breast cancer were individually matched to 1400 controls with unilateral breast cancer on date and age at diagnosis of the first breast cancer, race, and registry region, and counter-matched on radiation therapy. Each triplet comprised two women who received radiation therapy and one woman who did not. Radiation absorbed dose to the contralateral breast after initial treatment was estimated with a comprehensive dose reconstruction approach that included experimental measurements in anthropomorphic and water phantoms applying patient treatment parameters. Blood samples were collected from all participants for genetic analyses. CONCLUSIONS: Our study design improves the potential for detecting gene-environment interactions for diseases when both gene mutations and the environmental exposures of interest are rare in the general population. This is particularly applicable to the study of bilateral breast cancer because both radiation dose and genetic susceptibility have important etiologic roles, possibly by interactive mechanisms. By using counter-matching, we optimized the informativeness of the collected dosimetry data by increasing the variability of radiation dose within the case-control sets and enhanced our ability to detect radiation-genotype interactions.

The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer.

Breast development, one of the first signs of puberty, is closely associated with age at menarche; and early menarche is in turn a well-established risk factor for female breast cancer. We examined the relationships between the onset of puberty and gene variants for certain enzymes that regulate hormone metabolism among 137 healthy nine-year-old girls from two pediatric clinics. High-activity CYP17 alleles, involved in estrogen formation, and high-activity CYP1A2 and CYP1B1 alleles, whose gene products metabolize estradiol, were not associated with pubertal stage. High activity CYP3A4, but not CYP3A5, which primarily metabolizes testosterone, showed a striking association with the onset of puberty (adjusted odds ratio, 3.21; 95% confidence interval, 1.62-6.89 for the genotype 0-1-2 rapid alleles). Of the homozygous CYP3A4*1B/1B girls, 90% had reached puberty; whereas, for the low-activity homozygous CYP3A4*1A/1A individuals, only 40% had done so. In heterozygotes, 56% had reached puberty. CYP1B1, CYP3A4, and CYP3A5 rapid variants were more common in African-American than in Hispanic or Caucasian girls.

Characteristics of pubertal development in a multi-ethnic population of nine-year-old girls.

PURPOSE: Early age at menarche increases future disease risk. Secular decline in age at menarche has been attributed to body size characteristics, diet, and energy expenditure. Risk factors for puberty have been less frequently explored. METHODS: A cross-sectional study of 186 New York Metropolitan Area, 9-year-old girls (54 African-American, 70 Hispanic, 62 Caucasians) used interviewer-administered questionnaires to assess exposures. Height and weight were measured. Pediatricians assessed pubertal development according to Tanner stages. RESULTS: African-Americans were more likely than Caucasians to have achieved puberty as determined by breast or hair development (stage 2 or higher) [age-adjusted odds ratios and 95% confidence intervals = 4.91 (2.15-11.19) and 4.25 (1.85-9.77), respectively]. Pubertal development was similar among Hispanics and Caucasians. Adiposity and height were significantly positively associated with breast or hair development. More sedentary activity hours non-significantly increased the likelihood of hair development. Lower energy, but higher polyunsaturated fat, consumption were suggestive of an association with breast development. Vitamin C and hair development were inversely related. No other nutrients or physical activity measures were related to pubertal development. CONCLUSIONS: Results are consistent with height and adiposity being associated with pubertal development. Sedentary activity or diet might possibly influence maturation.

Prospective study of blood and tibia lead in women undergoing surgical menopause.

Despite the dramatic decline in environmental lead exposure in the United States during the past couple of decades, concern has been expressed regarding mobilization during menopause of existing lead stored in bone. To investigate whether bone lead concentrations decrease and blood lead levels increase, we conducted a prospective study of 91 women who were scheduled to undergo a bilateral oophorectomy for a benign condition at Mount Sinai Hospital in New York City during October 1994 through April 1999. We excluded women who were younger than 30 years of age or who were postmenopausal at the time of the surgery. We observed a small but significant increase in median blood lead levels between the baseline visit and the 6-month visit (0.4 microg/dL, p<0.0001), particularly for women who were not on estrogen replacement therapy (0.7 microg/dL, p=0.008). No significant change was observed in blood lead values between 6 and 18 months postsurgery, nor was there evidence of significant changes in tibia lead concentrations during the follow-up period. These findings do not point to substantial mobilization of lead from cortical bone during menopause.

In utero pesticide exposure, maternal paraoxonase activity, and head circumference.

Although the use of pesticides in inner-city homes of the United States is of considerable magnitude, little is known about the potentially adverse health effects of such exposure. Recent animal data suggest that exposure to pesticides during pregnancy and early life may impair growth and neurodevelopment in the offspring. To investigate the relationship among prenatal pesticide exposure, paraoxonase (PON1) polymorphisms and enzyme activity, and infant growth and neurodevelopment, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. In this report we evaluate the effects of pesticide exposure on birth weight, length, head circumference, and gestational age among 404 births between May 1998 and May 2002. Pesticide exposure was assessed by a prenatal questionnaire administered to the mothers during the early third trimester as well as by analysis of maternal urinary pentachlorophenol levels and maternal metabolites of chlorpyrifos and pyrethroids. Neither the questionnaire data nor the pesticide metabolite levels were associated with any of the fetal growth indices or gestational age. However, when the level of maternal PON1 activity was taken into account, maternal levels of chlorpyrifos above the limit of detection coupled with low maternal PON1 activity were associated with a significant but small reduction in head circumference. In addition, maternal PON1 levels alone, but not PON1 genetic polymorphisms, were associated with reduced head size. Because small head size has been found to be predictive of subsequent cognitive ability, these data suggest that chlorpyrifos may have a detrimental effect on fetal neurodevelopment among mothers who exhibit low PON1 activity.

Exposure to indoor pesticides during pregnancy in a multiethnic, urban cohort.

Evidence is growing that indoor pesticide exposure is of considerable magnitude in the United States and that pesticide concentrations may be especially high in urban areas. Of particular concern is exposure of pregnant women because animal data suggest that exposure to pesticides during pregnancy and early life may impair neurodevelopment in the offspring. To investigate the relationship between prenatal exposure to indoor pesticides and infant growth and development, we are conducting a prospective, multiethnic cohort study of mothers and infants delivered at Mount Sinai Hospital in New York City. This article provides data on pesticide exposure based on questionnaire items and analysis of maternal urinary metabolite levels among 386 women. Both the questionnaire and laboratory data revealed that exposure to indoor pesticides was considerable. The proportion of women estimated from questionnaire data as having been exposed during pregnancy to indoor pesticides (approximately 70%) was somewhat lower than the 80-90% of American households who reportedly used pesticides in previous surveys, but some of the latter surveys included both indoor and outdoor pesticide use. Urinary metabolite levels of 3,5,6-trichloro-2-pyridinol (TCPy; median = 11.3 micro g/g creatinine), phenoxybenzoic acid (PBA; median =19.3 micro g/g creatinine), and pentachlorophenol (PCP; median =7.3 micro g/g creatinine) were higher than those reported in other studies of adults in the United States. Furthermore, no associations were evident between the pesticide questionnaire data and the urinary metabolites. Assessments of sociodemographic and building characteristics with questionnaire data and the metabolite levels revealed no consistent trends. Significant temporal variations were observed for urinary PBA but not TCPy or PCP. The temporal variations for PBA were consistent with seasonal spraying of pyrethroid pesticides. These data underscore the need to assess the potentially adverse effects of pesticide exposure on fetuses and infants and the importance of finding alternative methods for pest management to reduce pesticide exposures.

Prenatal phthalate exposure and performance on the Neonatal Behavioral Assessment Scale in a multiethnic birth cohort.

We investigated the relationship between prenatal maternal urinary concentrations of phthalate metabolites and neonatal behavior in their 295 children enrolled in a multiethnic birth cohort between 1998 and 2002 at the Mount Sinai School of Medicine in New York City. Trained examiners administered the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) to children within 5 days of delivery. We measured metabolites of 7 phthalate esters in maternal urine that was collected between 25 and 40 weeks' gestation. All but two phthalate metabolites were over 95% detectable. We summed metabolites on a molar basis into low and high molecular weight phthalates. We hypothesized the existence of sex-specific effects from phthalate exposure a priori given the hormonal activity of these chemicals. Overall we found few associations between individual phthalate metabolites or their molar sums and most of the BNBAS domains. However, we observed significant sex-phthalate metabolite interactions (p<0.10) for the Orientation and Motor domains and the overall Quality of Alertness score. Among girls, there was a significant linear decline in adjusted mean Orientation score with increasing urinary concentrations of high molecular weight phthalate metabolites (B=-0.37, p=0.02). Likewise, there was a strong linear decline in their adjusted mean Quality of Alertness score (B=-0.48, p<0.01). In addition, boys and girls demonstrated opposite patterns of association between low and high molecular weight phthalate metabolite concentrations and motor performance, with some indication of improved motor performance with increasing concentration of low molecular weight phthalate metabolites among boys. This is the first study to report an association between prenatal phthalate exposure and neurological effects in humans or animals, and as such requires replication.

Prenatal organophosphate metabolite and organochlorine levels and performance on the Brazelton Neonatal Behavioral Assessment Scale in a multiethnic pregnancy cohort.

Prenatal exposures to organophosphate pesticides and polychlorinated biphenyls have been associated with abnormal neonatal behavior and/or primitive reflexes. In 1998-2002, the Mount Sinai Children's Environmental Health Center (New York City) investigated the effects of indoor pesticide use and exposure to polychlorinated biphenyls on pregnancy outcome and child neurodevelopment in an inner-city multiethnic cohort. The Brazelton Neonatal Behavioral Assessment Scale was administered before hospital discharge (n = 311). Maternal urine samples were analyzed for six dialkylphosphate metabolites and malathion dicarboxylic acid. A random subset of maternal peripheral blood samples from the entire cohort (n = 194) was analyzed for polychlorinated biphenyls and 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene. Malathion dicarboxylic acid levels above the limit of detection were associated with a 2.24-fold increase in the number of abnormal reflexes (95% confidence interval: 1.55, 3.24). Likewise, higher levels of total diethylphosphates and total dialkylphosphates were associated with an increase in abnormal reflexes, as was total dimethylphosphates after paraoxonase expression was considered. No adverse associations were found with polychlorinated biphenyl or 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene levels and any behavior. The authors uncovered additional evidence that prenatal levels of organophosphate pesticide metabolites are associated with anomalies in primitive reflexes, which are a critical marker of neurologic integrity.

Psychological trauma associated with the World Trade Center attacks and its effect on pregnancy outcome.

The destruction of the World Trade Center (WTC) on 11 September 2001 was a source of enormous psychological trauma that may have consequences for the health of pregnant women and their fetuses. In this report, we describe the impact of extreme trauma on the birth outcomes of women highly exposed to the WTC. We enrolled 187 women who were pregnant and living or working within close proximity to the WTC on 11 September. Among women with singleton pregnancies, 52 completed at least one psychological assessment prior to delivery. In adjusted multivariable models, both post-traumatic stress symptomatology (PTSS) and moderate depression were associated with longer gestational durations, although only PTSS was associated with decrements in infant head circumference at birth (beta=-0.07, SE=0.03, P=0.01). The impact of stress resulting from extreme trauma may be different from that which results from ordinary life experiences, particularly with respect to cortisol production. As prenatal PTSS was associated with decrements in head circumference, this may influence subsequent neurocognitive development. Long-term follow-up of infants exposed to extreme trauma in utero is needed to evaluate the persistence of these effects.

Predictors of organochlorines in New York City pregnant women, 1998-2001.

Organochlorine compounds (OCs) have been found widely in human tissues. However, levels have been rapidly declining since their virtual ban in the 1970s. We measured 1,1'-dichloro-2,2'-bis(4-chlorophenyl)ethylene (DDE), polychlorinated biphenyls (PCBs), and trans-nonachlor (TN) in 194 pregnant women in New York City and examined demographic and dietary predictors of their levels in serum. Serum OC levels were low (median microg/L: 0.64 DDE, 0.79 PCB); TN was largely below the level of detection (74%). In multivariate models, levels of OCs increased with age; DDE was higher in women not born in the US or Puerto Rico; PCB were higher in women who bought fresh fish and lower in those with higher body mass indices.

The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer.

The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative project's background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.1% (n = 1,508) and 62.8% (n = 1,556), respectively. Among case and control respondents who completed the interviewer-administered questionnaire, 98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3% donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random sample of case and control respondents who are long-term residents, samples of dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were collected. Established risk factors for breast cancer that were found to increase risk among Long Island women include lower parity, late age at first birth, little or no breast feeding, and family history of breast cancer. Factors that were found to be associated with a decreased likelihood that a respondent would donate blood include increasing age and past smoking; factors associated with an increased probability include white or other race, alcohol use, ever breastfed, ever use of hormone replacement therapy, ever use of oral contraceptives, and ever had a mammogram. Long-term residents (defined as 15+ years in the interview home) with environmental home samples did not differ from other long-term residents, although there were a number of differences in risk factor distributions between long-term residents and other participants, as anticipated.

Lead exposure among young urban women

Objetivo. En Estados Unidos, los niveles de plomo en sangre han declinado en todos los grupos de edad; no obstante, los grupos minoritarios que residen en áreas urbanas tienen un riesgo muy alto de poseer niveles elevados de dicho metal. Nuestro objetivo fue medir el nivel de plomo en mujeres jóvenes, en edad reproductiva, en la ciudad de Nueva York. También se describe el éxito en el reclutamiento de esa población para participar en un estudio de cohorte. Material y métodos. Las mujeres elegibles fueron aquellas que acudieron al centro de salud de la ciudad de Nueva York durante 1995-1998, tenían entre 18 y 25 años de edad y estaban sanas. El reclutamiento se llevó a cabo por los proveedores de salud, el coordinador del estudio y las mismas mujeres. Se administraron cuestionarios detallados y se obtuvieron muestras sanguíneas en donde se determinaron los niveles de plomo en sangre total, ferritina y hematocrito. Resultados. A la fecha se han reclutado 239 mujeres. La población es predominantemente de grupos minoritarios: 62 por ciento africanas-americanas, 33 por ciento hispánicas y 5 por ciento caucásicas-asiáticas. El promedio de edad es de 19.3 años. El reclutamiento de las participantes se hace invitando a las mujeres que previamente han aceptado participar en el estudio (55 por ciento). Algunas se enteraron del estudio por los proveedores de salud. El nivel medio de plomo fue de 2.1 1.7 m g/dl, el cual es consistente con las encuestas nacionales más recientes de Estados Unidos. Conclusiones. Los niveles de plomo en sangre son bajos en mujeres de grupos minoritarios, jóvenes, en edad reproductiva, que residen en zonas urbanas de la ciudad de Nueva York. En esta población el reclutamiento se incrementó sustancialmente con la ayuda de las participantes y la comunidad de proveedores de salud