Trends in long term exposure to propoxur and pyrethroids in young children in the Philippines.

BACKGROUND/AIM: Pesticides are neurotoxic and can adversely affect children's neurobehavioral outcome. Ongoing pesticide exposure has to be monitored in the study of long term outcome of pesticide adverse effects since changes in the type and amount of exposure can influence outcome. The aim of this paper is to describe the trend in long term pesticide exposure in children through the analysis of pesticides in their hair. PATIENTS AND METHODS: As part of an NIH study on the long term effects of pesticide exposure in young children, ongoing exposure to pesticides was determined by the analysis of children's hair for propoxur and pyrethroids by gas chromatography/mass spectrometry at 2, 4 and 6 years of age. RESULTS: There were significant changes in the prevalence and concentration of propoxur and pyrethroids in children's hair at 2, 4 and 6 years of age. At ages 2 and 4 years, the prevalence of propoxur exposure increased from 12.4% to 24.1% (p<0.001) but dramatically decreased to 1.7% at 6 years (p<0.001). For bioallethrin, the prevalence of exposure steadily increased from 2 years (0.7%, p<0.001) to 4 years (12.4%, p<0.001) and to 6 years (18.4% p<0.001). Exposure to transfluthrin significantly increased from 4 years (1.0%) to 6 years (9.2%, p<0.001). There were also significantly higher median concentrations of bioallethrin at 2 compared to 4 years and for propoxur at 2 years compared to 6 years. Between 4 and 6 years, there was a higher median concentration of propoxur at 4 compared to 6 years and for transfluthrin and bioallethrin, at 6 compared to 4 years. CONCLUSION: Changes in the prevalence and concentration of exposure to propoxur and pyrethroids in children at 2, 4 and 6 years of age are related to the progress in ambulation of young children and to changes in the formulation of home spray pesticides. Thus, periodic monitoring of pesticide exposure is necessary when studying the long term effects of pesticide exposure in the neurodevelopment of young children.

Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age.

OBJECTIVE: Our aim was to determine the effects of fetal exposure to propoxur and pyrethroids, on child neurodevelopment at 2 years of age. PATIENTS AND METHODS: Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin are used. To detect prenatal exposure to these pesticides, maternal hair and blood, infant's hair, cord blood, and meconium were analyzed for the pesticides by gas chromatography/mass spectrometry. Infants were examined at 2 years of age with 95.1% follow up rate and their neurodevelopment outcome was assessed by the Griffiths mental developmental scale (N=754). RESULTS: Meconium analysis was the most sensitive method to detect fetal exposure to pesticides and exposure was highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin, transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed to determine the effects of fetal exposure to propoxur and pyrethroids on the child's neurodevelopment at 24 months of age while controlling for confounders. Only singletons and those with complete data for the path analysis were included (N=696). Using a path analysis model, there was a significant negative (ß=-0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and motor development at 2 years of age after controlling for confounders, e.g., infant gender, socioeconomic status, maternal intelligence, home stimulation (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age. CONCLUSION: At 2 years of age, prenatal exposure to propoxur was associated with poorer motor development in children.

Analysis of House Dust and Children's Hair for Pesticides: A Comparison of Markers of Ongoing Pesticide Exposure in Children.

BACKGROUND/AIM: The long term study of the adverse effects of pesticides on child neuro development requires monitoring not only of initial, but ongoing pesticide exposure. Our aim was to compare house dust and children's hair as environmental and biological markers of ongoing pesticide exposure in children. DESIGN/METHODS: In a continuing NIH study on the adverse effects of prenatal pesticide exposure on child neurodevelopment, ongoing pesticide exposure after birth was measured in swept house dust and hair in the children at 4 years of age for propoxur and pyrethroids (transfluthrin, bioallethrin, cyfluthrin and cypermethrin) by gas chromatography/mass spectrometry. The prevalence and concentration of pesticides in the two matrices were compared. RESULTS: Prevalence of propoxur was higher in hair compared to house dust (p<0.001) whereas prevalence of the pyrethroids was higher (p<0.001) in house dust. The overall concentrations of the pyrethroids were also higher (p<0.007) in house dust compared to hair. There was a significant (p<0.001) correlation between dust and hair for bioallethrin and cypermethrin. CONCLUSIONS: Ongoing exposure of children to environmental pesticides is sensitively detected by analysis of children's hair and house dust. However, prevalence of propoxur was higher in hair compared to swept house dust, but the opposite was found for the pyrethroids. Thus, both matrices should be analyzed. There was a significant (p<0.001) correlation between house dust and hair for bioallethrin and cypermethrin.

Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure to environmental pesticides.

OBJECTIVE: The aim of this study was to determine optimum biomarkers to detect fetal exposure to environmental pesticides by the simultaneous analysis of maternal (hair and blood) and infant (cord blood, infant hair or meconium) matrices and to determine if a combination of these biomarkers will further increase the detection rate. PATIENTS AND METHODS: Pregnant women were prospectively recruited from an agricultural site in the Philippines with substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Maternal hair and blood were obtained at midgestation and at delivery and infant hair, cord blood and meconium were obtained after birth. All samples were analyzed by gas chromatography/mass spectrometry (GC/MS) for the above pesticides and some of their metabolites. RESULTS: A total of 598 mother/infant dyads were included in this report. The highest rates of pesticide exposure were detected in meconium (23.2% to propoxur, 2.0% to pretilachlor, 1.7% to cypermethrin, 0.8% to cyfluthrin, 0.7% to 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and 0.3% to malathion and bioallethrin) and in maternal hair (21.6% to propoxur, 14.5% to bioallethrin, 1.3% to malathion, 0.8% to DDT, 0.3% to chlorpyrifos and 0.2% to pretilachlor). Combined analysis of maternal hair and meconium increased detection rate further to 38.5% for propoxur and to 16.7% for pyrethroids. Pesticide metabolites were rarely found in any of the analyzed matrices. CONCLUSIONS: There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticides, propoxur and pyrethroids. Analysis of meconium for pesticides was the single most sensitive measure of exposure. However, combined analysis of maternal hair and meconium significantly increased the detection rate. A major advantage of analyzing maternal hair is that prenatal pesticide exposure in the mother can be detected and intervention measures can be initiated to minimize further exposure of the fetus to pesticides.

An epidemiologic study comparing fetal exposure to tobacco smoke in three Southeast Asian countries.

The high prevalence of smoking in Southeast Asia (SEA) means pregnant women face exposure to tobacco smoke that may affect the health of their fetus. This study determined fetal exposure to tobacco smoke by meconium analysis for cotinine in 3 locations in SEA: Bulacan Province, Philippines (N=316), Bangkok, Thailand (N=106) and Singapore City (N=61). Maternal exposure to tobacco smoke was 71.1% (1.3% active; 69.8% passive) in Bulacan, 57.5% (0.9% active; 58.6% passive) in Bangkok and 54.1% (11.5% active; 42.0% passive) in Singapore. Fetal exposure to tobacco smoke (by meconium analysis) was 1.3% (Bulacan), 4.7% (Bangkok) and 13.1% (Singapore); however, a large proportion of infants who tested positive for cotinine (65%) were born to mothers who gave no history of either active or passive exposure to environmental tobacco smoke. Fetal exposure to tobacco smoke is a major health problem.

A comparison of infant hair, cord blood and meconium analysis to detect fetal exposure to environmental pesticides.

OBJECTIVE: The detection of fetal exposure to environmental pesticides is important because many of the pesticides are neurotoxicants and fetal exposure to these compounds can adversely affect prenatal and subsequent neurodevelopment. The aim of this study was to determine, by the comparative analysis of infant hair, cord blood and meconium, the most sensitive matrix to detect fetal exposure to pesticides. PATIENTS AND METHODS: Pregnant women were prospectively recruited from an agricultural site in the Philippines where a preliminary survey indicated a substantial use at home and in the farm of the following pesticides: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin. Infant hair, cord blood and meconium were obtained after birth and were analyzed by gas chromatography/mass spectrometry for the above compounds, including lindane and 1,1,1-trichloro-2,2-bis, p-chlorophenylethane (DDT) and some of their known metabolites. RESULTS: A total of 638 infants were included in the study. The highest exposure rate to pesticides was detected in meconium (23.8% to propoxur, 1.9% to pretilachlor, 1.9% to cypermethrin, 0.8% to cyfluthrin, 0.6% to DDT and 0.3% to malathion and bioallethrin). Cord blood was only positive for propoxur (1.9%) whereas infant hair was only positive for chlorpyrifos (0.2%). The highest exposure was to household pesticide (propoxur). The frequency and concentration of pesticides were compared in the three matrices and there was a significantly higher frequency and concentration of propoxur, pretilachlor, DDT, cyfluthrin and cypermethrin in meconium compared to cord blood and infant hair. Pesticide metabolites were not found in any of the matrices analyzed, except in one meconium sample which was positive for 4,4' dichlorodiphenyldichloro ethylene (DDE), a DDT metabolite. CONCLUSIONS: There is significant exposure of the pregnant woman and her fetus to pesticides, particularly to the home pesticide, propoxur. Our study has demonstrated that among cord blood, meconium or infant hair, meconium is the most sensitive matrix to analyze for fetal exposure to pesticides. The accumulation of pesticides in meconium, the ease of meconium collection and the large amount of meconium that could be collected are factors that contribute to the increased sensitivity of this matrix.

Adaptation of the Behavioral Assessment and Research System (BARS) for evaluating neurobehavioral performance in Filipino children.

Neurobehavioral tests have long been used to assess health effects in exposed working adult populations. The heightened concern over the potential impact of environmental exposures on neurological functioning in children has led to the development of test batteries for use with children. There is a need for reliable, easy-to-administer batteries to assess neurotoxic exposure in children. One such test battery previously validated with Spanish- and English-speaking children ages 4 and older, combines computerized tests from the Behavioral Assessment and Research System (BARS) with non-computerized tests. The goal of the present study was to determine the feasibility of using standardized neurobehavioral tests in preschool and school-aged Filipino children. Test instructions were translated into the vernacular, Tagalog or Tagalog-English ("Taglish") and some instructions and materials were modified to be appropriate for the target populations. The battery was administered to 4-6-year-old Filipino children (N=50). The performance of the Filipino children was compared to data previously collected from Spanish- and English-speaking children tested in the US. The majority of children had no difficulty completing the tests in the battery with the exception of the Symbol-Digit test and Digit Span-reverse. The three groups showed similar patterns of performance on the tests and the older children performed better than the younger children on all of the tests. The findings from this study demonstrate the utility of using this test battery to assess cognitive and motor performance in Filipino children. Tests in the battery assess a range of functions and the measures are sensitive to age differences. The current battery has been utilized in several cultures and socio-economic status classes, with only minor modifications needed. This study demonstrates the importance of pilot testing the methods before use in a new population, to ensure that the test is valid for that culture.

Persistent pulmonary hypertension of the newborn: pathogenesis, etiology, and management.

Persistent pulmonary hypertension of the newborn (PPHN) is characterized by severe hypoxemia shortly after birth, absence of cyanotic congenital heart disease, marked pulmonary hypertension, and vasoreactivity with extrapulmonary right-to-left shunting of blood across the ductus arteriosus and/or foramen ovale. In utero, a number of factors determine the normally high vascular resistance in the fetal pulmonary circulation, which results in a higher pulmonary compared with systemic vascular pressure. However, abnormal conditions may arise antenatally, during, or soon after birth resulting in the failure of the pulmonary vascular resistance to normally decrease as the circulation evolves from a fetal to a postnatal state. This results in cyanosis due to right-to-left shunting of blood across normally existing cardiovascular channels (foramen ovale or ductus arteriosus) secondary to high pulmonary versus systemic pressure. The diagnosis is made by characteristic lability in oxygenation of the infant, echocardiographic evidence of increased pulmonary pressure, with demonstrable shunts across the ductus arteriosus or foramen ovale, and the absence of cyanotic heart disease lesions. Management of the disease includes treatment of underlying causes, sedation and analgesia, maintenance of adequate systemic blood pressure, and ventilator and pharmacologic measures to increase pulmonary vasodilatation, decrease pulmonary vascular resistance, increase blood and tissue oxygenation, and normalize blood pH. Inhaled nitric oxide has been one of the latest measures to successfully treat PPHN and significantly reduce the need for extracorporeal membrane oxygenation.

Maternal hair--an appropriate matrix for detecting maternal exposure to pesticides during pregnancy.

The detection of exposure of pregnant women to toxicants in the environment is important because these compounds can be harmful to the health of the woman and her fetus. The aim of this study was to analyze for pesticides/herbicides in paired maternal hair and blood samples to determine the most appropriate matrix for detecting maternal exposure to these compounds. A total of 449 pregnant women were prospectively recruited at midgestation from an agricultural site in the Philippines where a preliminary survey indicated significant use at home and on the farm of the following compounds: propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon, and transfluthrin. Paired maternal hair and blood samples were obtained from each subject upon recruitment into the study (midgestation) and at birth and were analyzed for the above compounds, as well as lindane and DDT [1,1,1-trichloro-2-2-bis(p-chlorophenyl) ethane], and some of their known metabolites by gas chromatography/mass spectrometry. The highest exposure rate was seen for propoxur and bioallethrin and maternal hair analysis provided the highest detection rate for these two compounds, compared to blood, at both time periods: (1) At midgestation, 10.5% positive for propoxur in hair compared to 0.7% in blood (P<0.001) and for bioallethrin, 11.9% positive in hair compared to 0% in blood (P < or = 0.001), and (2) at birth, 11.8% positive for propoxur in hair compared to 4% in blood (P < or = 0.001) and for bioallethrin, 7.8% in hair compared to 0% in blood (P < or = 0.001). A small number of maternal hair samples were also positive for malathion, chlorpyrifos, pretilachlor, and DDT. Only a few of the pesticide metabolites were detected, principally 3-phenoxybenzoic acid, malathion monocarboxylic acid, and DDE [1,1,dichloro-2-2-bis(p-chlorophenyl)ethylene], and they were mostly found in maternal blood. There was a significant association between the use of the home spray pesticide, Baygon, and propoxur in maternal hair at birth (P=0.001) and between the use of a slow-burning mosquito coil and the presence of bioallethrin in maternal hair at midgestation and at birth (P=0.001, P < or = 0.041, respectively). There is significant exposure of the pregnant woman to pesticides, particularly to pesticides that are used at home. Our study demonstrates the advantages of analyzing maternal hair as a readily available biologic matrix for studying maternal exposure to toxicants in the environment, compared to blood. For propoxur, there was a 3- to 15-fold higher detection rate of the pesticide in maternal hair as compared to blood. As for the other pesticides, bioallethrin, malathion, chlorpyrifos, and DDT were exclusively found in maternal hair compared to blood. On the other hand, pesticide metabolites were infrequently found in maternal hair or maternal blood. Pesticides in blood most likely represent acute exposure, whereas pesticides in hair represent past and/or concurrent exposure. The high sensitivity, wide window of exposure, availability, and ease of hair collection are distinct advantages in using hair to detect exposure to pesticides among pregnant women. However, pesticides in maternal hair may also be secondary to passive exposure and therefore not truly representative of the internal pesticide dose. Finally, the analysis of maternal hair for pesticides as an index of maternal exposure to pesticides in the environment allows the institution of measures to prevent further exposure during pregnancy.