Robin Garfinkel

Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children.

OBJECTIVE. The purpose of this study was to investigate the impact of prenatal exposure to chlorpyrifos on 3-year neurodevelopment and behavior in a sample of inner-city minority children. METHODS. As part of an ongoing prospective cohort study in an inner-city minority population, neurotoxicant effects of prenatal exposure to chlorpyrifos were evaluated in 254 children through the first 3 years of life. This report examined cognitive and motor development at 12, 24, and 36 months (measured with the Bayley Scales of Infant Development II) and child behavior at 36 months (measured with the Child Behavior Checklist) as a function of chlorpyrifos levels in umbilical cord plasma. RESULTS. Highly exposed children (chlorpyrifos levels of >6.17 pg/g plasma) scored, on average, 6.5 points lower on the Bayley Psychomotor Development Index and 3.3 points lower on the Bayley Mental Development Index at 3 years of age compared with those with lower levels of exposure. Children exposed to higher, compared with lower, chlorpyrifos levels were also significantly more likely to experience Psychomotor Development Index and Mental Development Index delays, attention problems, attention-deficit/hyperactivity disorder problems, and pervasive developmental disorder problems at 3 years of age. CONCLUSIONS. The adjusted mean 36-month Psychomotor Development Index and Mental Development Index scores of the highly and lower exposed groups differed by only 7.1 and 3.0 points, respectively, but the proportion of delayed children in the high-exposure group, compared with the low-exposure group, was 5 times greater for the Psychomotor Development Index and 2.4 times greater for the Mental Development Index, increasing the number of children possibly needing early intervention services.

Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides.

The contribution of maternal age to racial disparities in birthweight: A multilevel perspective

OBJECTIVES This study assessed the contribution of age and other risk factors to racial disparities in rates of moderately low birthweight (MLBW; 1500-2499 g) and very low birthweight (VLBW; <1500 g). METHODS Logistic regression models were developed to determine the effects on MLBW and VLBW of maternal age, race, and poverty, adjusting for birth order, smoking, substance abuse, marital status, and educational level. The sample consisted of 158 174 singleton births to US-born African American and White women in New York City between 1987 and 1993. RESULTS The effects of maternal age on MLBW varied by race and poverty, with the most extreme effects among poor African American women. The effects of maternal age on VLBW also varied by race, but these effects were not moderated by poverty. Community poverty had a significant effect on MLBW among African American women, but no effect on VLBW. The adverse effect of older maternal age on MLBW and VLBW did not vary with community poverty. CONCLUSIONS Older maternal age is associated with reduced birthweight among infants born to African American women, and the age effect is exacerbated by individual poverty.

Prenatal Exposure to Airborne Polycyclic Aromatic Hydrocarbons and Risk of Intrauterine Growth Restriction

Background Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants generated by combustion of organic material, including fossil fuel. Objectives It has been an open question whether prenatal exposure to air pollution in general and PAHs in particular significantly increases the risk of intrauterine growth restriction, including small size for gestational age (SGA), and preterm delivery. Here, we have examined this hypothesis in a cohort of mothers and newborns in New York City. Methods Subjects were young, nonsmoking, healthy African-American (n = 224) and Dominican (n = 392) mother–newborn pairs residing in New York City whose prenatal PAH exposures were estimated by personal air monitoring. Questionnaire and medical record data were obtained. Results A 1 natural-log (ln)-unit increase in prenatal PAH exposure was associated with a 2-fold increase in risk of symmetric intrauterine growth restriction (i.e., SGA and fetal growth ratio < 85%) among full-term African Americans (p < 0.05). Preterm delivery risk was 5-fold greater among African Americans per ln-unit increase in prenatal PAH exposure. The same unit increase in exposure significantly increased the ratio of head circumference to birth weight by 0.04% in African Americans. These effects were not observed in Dominicans. Conclusion Prenatal PAH exposure is likely to contribute to the occurrence of SGA as well as preterm births among African Americans. The lack of an association in Dominicans might reflect modification of the risk by healthful cultural practices among recent Dominican immigrants. Given that PAHs are globally generated and distributed pollutants, our observations have potential implications for environmental health and energy policies.

Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban, low-income cohort

Background Acetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor allele variant in the glutathione S transferase Pi gene (GSTP1). We hypothesised that prenatal acetaminophen exposure would predict wheeze at age 5 years in an inner-city minority cohort and examined whether this association was modified by common polymorphisms in genes related to the glutathione pathway. Methods An ongoing population-based birth cohort study of Dominican Republic and African-American children in New York prospectively assessed the use of analgesics during pregnancy and current wheeze at age 5 years in 301 children. Genotyping was conducted for GST polymorphisms. Binomial regression was used to adjust for potential confounders including postnatal acetaminophen use. Results 34% of mothers reported acetaminophen use during pregnancy and 27% of children had current wheeze at 5 years. Prenatal exposure to acetaminophen predicted current wheeze (multivariate relative risk 1.71; 95% CI 1.20 to 2.42; p=0.003), and the risk increased monotonically with increasing number of days of prenatal acetaminophen exposure (p trend <0.001). 68% of children had at least one copy of the GSTP1 minor allele (Val). The risk of wheeze was modified by GSTP1 (additive interaction p=0.009) and was observed only among children with the GSTP1 minor allele. Conclusions Prenatal exposure to acetaminophen predicted wheeze at age 5 years in an inner-city minority cohort. The risk was modified by a functional polymorphism in GSTP1, suggesting a mechanism involving the glutathione pathway.

Within- and Between-Home Variability in Indoor-Air Insecticide Levels during Pregnancy among an Inner-City Cohort from New York City

Background Residential insecticide use is widespread in the United States, but few data are available on the persistence and variability in levels in the indoor environment. Objective The study aim was to assess within- and between-home variability in indoor-air insecticides over the final 2 months of pregnancy among a cohort of African-American and Dominican women from New York City. Methods Women not employed outside the home were enrolled between February 2001 and May 2004 (n = 102); 9 insecticides and an adjuvant were measured in 48-hr personal air samples and 2-week integrated indoor air samples collected sequentially for 7.0 ± 2.3 weeks (n = 337 air samples). Results Sixty-one percent of the women reported using pest control during the air samplings. Chlorpyrifos, diazinon, and propoxur were detected in 99–100% of personal and indoor samples (range, 0.4–641 ng/m3). Piperonyl butoxide (a pyrethroid adjuvant) was detected in 45.5–68.5% (0.2–608 ng/m3). There was little within-home variability and no significant difference in air concentrations within homes over time (p ≥ 0.2); between-home variability accounted for 88% of the variance in the indoor air levels of propoxur, 92% in chlorpyrifos, 94% in diazinon, and 62% in piperonyl butoxide (p < 0.001). Indoor and maternal personal air insecticide levels were highly correlated (r = 0.7–0.9, p < 0.001). Diazinon and chlorpyrifos levels declined 5-fold between 2001 and 2004 but were detected in all homes 1.5 and 2.5 years, respectively, after the U.S. Environmental Protection Agency ban on their residential use. Conclusion Results showed that the insecticides were persistent in the home with little variability in air concentrations over the 2 months and contributed to chronic maternal inhalation exposures during pregnancy.

Ambient Metals, Elemental Carbon, and Wheeze and Cough in New York City Children through 24 Months of Age

RATIONALE The effects of exposure to specific components of ambient fine particulate matter (PM(2.5)), including metals and elemental carbon (EC), have not been fully characterized in young children. OBJECTIVES To compare temporal associations among PM(2.5); individual metal constituents of ambient PM(2.5), including nickel (Ni), vanadium (V), and zinc (Zn); and EC and longitudinal reports of respiratory symptoms through 24 months of age. METHODS Study participants were selected from the Columbia Center for Childrens Environmental Health birth cohort recruited in New York City between 1998 and 2006. Respiratory symptom data were collected by questionnaire every 3 months through 24 months of age. Ambient pollutant data were obtained from state-operated stationary monitoring sites located within the study area. For each subject, 3-month average inverse-distance weighted concentrations of Ni, V, Zn, EC, and PM(2.5) were calculated for each symptom-reporting period based on the questionnaire date and the preceding 3 months. Associations between pollutants and symptoms were characterized using generalized additive mixed effects models, adjusting for sex, ethnicity, environmental tobacco smoke exposure, and calendar time. MEASUREMENTS AND MAIN RESULTS Increases in ambient Ni and V concentrations were associated significantly with increased probability of wheeze. Increases in EC were associated significantly with cough during the cold/flu season. Total PM(2.5) was not associated with wheeze or cough. CONCLUSIONS These results suggest that exposure to ambient metals and EC from heating oil and/or traffic at levels characteristic of urban environments may be associated with respiratory symptoms among very young children.

Separation/Divorce and Child and Adolescent Completed Suicide

OBJECTIVE To investigate factors that may modify the effect of separation/divorce on youth suicide. METHOD A case-control, psychological autopsy study of 120 of 170 consecutive suicides younger than age 20 and 147 community age-, sex-, and ethnic group-matched controls living in the greater New York area was conducted. Fifty-eight suicide victims and 49 community controls came from nonintact families of origin, indicating the permanent separation/divorce of the biological parents. Potential modifiers of separation/divorce include youths age at separation, custodial parents remarriage, nonresidential parents frequency of contact, parent-child relationships, and parental psychopathology. RESULTS The relatively small impact of separation/divorce was further diminished after accounting for parental psychopathology. An interaction of separation/divorce and the father-child relationship emerged. CONCLUSION The dramatic increase in youth suicide during the past three decades seems unlikely to be attributable to the increase in divorce rates.

Polycyclic aromatic hydrocarbon metabolite levels and pediatric allergy and asthma in an inner-city cohort

Miller RL, Garfinkel R, Lendor C, Hoepner L, Li Z, Romanoff L, Sjodin A, Needham L, Perera FP, Whyatt RM. Polycyclic aromatic hydrocarbon metabolite levels and pediatric allergy and asthma in an inner‐city cohort. 
Pediatr Allergy Immunol 2010: 21: 260–267.
© 2009 John Wiley & Sons A/S

A Biomarker Validation Study of Prenatal Chlorpyrifos Exposure within an Inner-City Cohort during Pregnancy

Background We previously documented significant decreases in chlorpyrifos concentrations in maternal personal and indoor air samples among pregnant African-American and Dominican women from New York City after the 2000–2001 restrictions on its residential use. Objective We undertook a biomarker validation study within the same cohort to evaluate trends over time in multiple biomarkers of prenatal chlorpyrifos exposure. Methods Subjects were enrolled between February 2001 and May 2004 (n = 102). We measured 3,5,6-trichloro-2-pyridinol (TCPy) in postpartum meconium (n = 83), repeat prenatal maternal spot urine samples (n = 253), and postnatal urine from the mothers (n = 73) and newborns (n = 59). We measured chlorpyrifos in postnatal maternal (n = 92) and umbilical cord (n = 65) blood. Results We did not detect TCPy in infant urine, but all other biomarkers showed a highly significant decrease in detection frequencies (χ2 = 7.8–34.0, p ≤ 0.005) and mean ranks (p ≤ 0.006, Kruskal–Wallis) among subjects enrolled in 2003–2004 compared with those enrolled in 2001–2002. Chlorpyrifos in maternal personal and indoor air declined 2- to 3-fold over the same period (p < 0.05). In 2001–2002 samples, TCPy levels in repeat prenatal urine were positively correlated (r = 0.23–0.56), but within-subject variability exceeded between-subject variability (intraclass correlation coefficient = 0.43); indoor air levels explained 19% of the variance in prenatal urine TCPy (p = 0.001). Meconium TCPy concentrations were positively correlated with chlorpyrifos in maternal and cord blood (r = 0.25–0.33, p < 0.05) and with TCPy in maternal urine (r = 0.31, p < 0.01). Conclusions Results suggest the biomarkers are reliable dosimeters to differentiate between groups with prenatal chlorpyrifos exposures varying by a factor of 2 or more and vividly illustrate the efficacy of residential restriction on chlorpyrifos to reduce the internal dose during pregnancy.