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Organophosphate Pesticide Exposure in Pregnancy in Association with Ultrasound and Delivery Measures of Fetal Growth.

ABSTRACT: BACKGROUND:Perturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size in utero in combination with measures from delivery. METHODS:Within Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Netherlands, we measured dialkyl phosphates (DAPs), OP metabolites, in urine samples from early, middle, and late pregnancy and created a subject-specific average to estimate OP exposure ([Formula: see text]). Ultrasound measures of head circumference, femur length, and estimated fetal weight from middle and late pregnancy and delivery measures were converted to standard deviation scores (SDS). Associations with DAP average were examined in linear mixed effects models that included an interaction term between gestational age at measurement and DAP average to investigate whether the relationship differed over time. Windows of vulnerability to exposure were assessed by modeling urinary DAPs from each visit in relation to growth measurements. RESULTS:A 10-fold increase in average DAPs was associated with a [Formula: see text] SDS decrease in fetal length (95% [Formula: see text], [Formula: see text]) and a [Formula: see text] SDS decrease in estimated fetal weight (95% [Formula: see text], [Formula: see text]) at 20 weeks of gestation. These differences corresponded to 5% and 6% decreases relative to the mean. Effect estimates were greatest in magnitude for DAP concentrations measured early in pregnancy. Associations between average DAPs and growth measures at delivery were positive but not significant for head circumference and length and were null for weight. CONCLUSIONS:Maternal urinary DAPs were associated with decreased fetal weight and length measured during mid-pregnancy, but not at delivery. https://doi.org/10.1289/EHP4858.

SUBMITTER: Ferguson KK

PROVIDER: S-EPMC6792347 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Organophosphate Pesticide Exposure in Pregnancy in Association with Ultrasound and Delivery Measures of Fetal Growth.

Ferguson Kelly K KK van den Dries Michiel A MA Gaillard Romy R Pronk Anjoeka A Spaan Suzanne S Tiemeier Henning H Jaddoe Vincent W V VWV

Environmental health perspectives 20190816 8

<h4>Background</h4>Perturbations in fetal growth may have adverse consequences for childhood and later life health. Organophosphate pesticide (OP) exposure has been associated with reduced birth weight at delivery but results are not consistent. We investigated this question by utilizing ultrasound measures of size <i>in utero</i> in combination with measures from delivery.<h4>Methods</h4>Within Generation R, a population-based prospective cohort conducted between 2002 and 2006 in Rotterdam, Net ...[more]

PMID: 31419153

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Project description:BackgroundAir pollution exposure during pregnancy might have trimester-specific effects on fetal growth.ObjectiveWe prospectively evaluated the associations of maternal air pollution exposure with fetal growth characteristics and adverse birth outcomes in 7,772 subjects in the Netherlands.MethodsParticulate matter with an aerodynamic diameter < 10 μm (PM10) and nitrogen dioxide (NO2) levels were estimated using dispersion modeling at the home address. Fetal head circumference, length, and weight were estimated in each trimester by ultrasound. Information on birth outcomes was obtained from medical records.ResultsIn cross-sectional analyses, NO2 levels were inversely associated with fetal femur length in the second and third trimester, and PM10 and NO2 levels both were associated with smaller fetal head circumference in the third trimester [-0.18 mm, 95% confidence interval (CI): -0.24, -0.12 mm; and -0.12 mm, 95% CI: -0.17, -0.06 mm per 1-μg/m3 increase in PM10 and NO2, respectively]. Average PM10 and NO2 levels during pregnancy were not associated with head circumference and length at birth or neonatally, but were inversely associated with birth weight (-3.6 g, 95% CI: -6.7, -0.4 g; and -3.4 g, 95% CI: -6.2, -0.6 g, respectively). Longitudinal analyses showed similar patterns for head circumference and weight, but no associations with length. The third and fourth quartiles of PM10 exposure were associated with preterm birth [odds ratio (OR) = 1.40, 95% CI: 1.03, 1.89; and OR = 1.32; 95% CI: 0.96, 1.79, relative to the first quartile]. The third quartile of PM10 exposure, but not the fourth, was associated with small size for gestational age at birth (SGA) (OR = 1.38; 95% CI: 1.00, 1.90). No consistent associations were observed for NO2 levels and adverse birth outcomes.ConclusionsResults suggest that maternal air pollution exposure is inversely associated with fetal growth during the second and third trimester and with weight at birth. PM10 exposure was positively associated with preterm birth and SGA.

Project description:BackgroundPrenatal exposure to bisphenol A (BPA) and phthalates may affect fetal growth; however, previous findings are inconsistent and based on few studies.ObjectivesWe assessed whether prenatal exposure to BPA and phthalates was associated with fetal growth in a Spanish birth cohort of 488 mother-child pairs.MethodsWe measured BPA and eight phthalates [four di(2-ethylhexyl) phthalate metabolites (DEHPm), mono-benzyl phthalate (MBzP), and three low-molecular-weight phthalate metabolites (LMWPm)] in two spot-urine samples collected during the first and third trimester of pregnancy. We estimated growth curves for femur length (FL), head circumference (HC), abdominal circumference (AC), biparietal diameter (BPD), and estimated fetal weight (EFW) during pregnancy (weeks 12-20 and 20-34), and for birth weight, birth length, head circumference at birth, and placental weight.ResultsOverall, results did not support associations of exposure to BPA or DEHPm during pregnancy with fetal growth parameters. Prenatal MBzP exposure was positively associated with FL at 20-34 weeks, resulting in an increase of 3.70% of the average FL (95% CI: 0.75, 6.63%) per doubling of MBzP concentration. MBzP was positively associated with birth weight among boys (48 g; 95% CI: 6, 90) but not in girls (-27 g; 95% CI: -79, 25) (interaction p-value = 0.04). The LMWPm mono-n-butyl phthalate (MnBP) was negatively associated with HC at 12-20 pregnancy weeks [-4.88% of HC average (95% CI: -8.36, -1.36%)].ConclusionsThis study, one of the first to combine repeat exposure biomarker measurements and multiple growth measures during pregnancy, finds little evidence of associations of BPA or phthalate exposures with fetal growth. Phthalate metabolites MBzP and MnBP were associated with some fetal growth parameters, but these findings require replication.CitationCasas M, Valvi D, Ballesteros-Gomez A, Gascon M, Fernández MF, Garcia-Esteban R, Iñiguez C, Martínez D, Murcia M, Monfort N, Luque N, Rubio S, Ventura R, Sunyer J, Vrijheid M. 2016. Exposure to bisphenol A and phthalates during pregnancy and ultrasound measures of fetal growth in the INMA-Sabadell cohort. Environ Health Perspect 124:521-528; http://dx.doi.org/10.1289/ehp.1409190.

Project description:BackgroundEpidemiologic studies suggest that maternal organophosphorus (OP) pesticide exposure is associated with poorer fetal growth, but findings are inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in detoxification of OPs, could be an effect modifier in this association.MethodsThe study population included 470 pregnant women enrolled in the CHAMACOS Study, a longitudinal cohort study of mothers and children living in an agricultural region of California. We analyzed urine samples collected from mothers twice during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1(192) and PON1(-108)) and enzyme activity (paraoxonase and arylesterase). Infant birth weight, head circumference, and gestational age were obtained from medical records.ResultsInfants' PON1 genotype and activity were associated with birth outcome, but mothers' were not. Infants with the susceptible PON1(-108TT) genotype had shorter gestational age (β = -0.5 weeks, 95% Confidence Interval (CI): -0.9, 0.0) and smaller head circumference (β = -0.4 cm, 95% CI: -0.7, 0.0) than those with the PON1(-108CC) genotype. Infants' arylesterase and paraoxonase activity were positively associated with gestational age. There was some evidence of effect modification with DAPs: maternal DAP concentrations were associated with shorter gestational age only among infants of the susceptible PON1(-108TT) genotype (p-value(interaction) = 0.09). However, maternal DAP concentrations were associated with larger birth weight (p-value(interaction) = 0.06) and head circumference (p-value(interaction)<0.01) in infants with non-susceptible genotypes.ConclusionsInfants whose PON1 genotype and enzyme activity levels suggested that they might be more susceptible to the effects of OP pesticide exposure had decreased fetal growth and length of gestation. PON1 may be another factor contributing to preterm or low birth weight birth.

Project description:BackgroundOrganophosphates (OP) are widely used insecticides that acutely inhibit acetylcholinesterase enzyme activity. There is great interest in improving the understanding of molecular mechanisms related to chronic OP exposure induced toxicity. We aim to elucidate epigenetic changes associated with OP exposure, using untargeted analysis of genome-wide DNA methylation data.MethodsIn a population-based case control study of Parkinson's disease (PD), we assessed ambient OP exposure via residential and workplace proximity to commercial applications. We investigated associations between OP exposure and genome-wide DNA methylation (Illumina 450 k) in 580 blood samples (342 PD patients, 238 controls) and 259 saliva samples (128 patients, 131 controls). To identify differential methylation related to OP exposure, we controlled for age, sex, European ancestry, and PD status; in addition, we stratified by disease status.ResultsWe identified 70 genome-wide significant CpGs, including cg01600516 in ALOX12 (cor = 0.27, p = 1.73E-11) and two CpGs in HLA genes, cg01655658 (cor = -0.24, p = 2.80E-09) in HLA-L (pseudogene) and cg15680603 (cor = 0.20, p = 7.94E-07) in HLA-DPA1. Among the 70 CpGs located in 41 genes, 14 were also differentially methylated in saliva samples. The most overrepresented pathway was the nicotinic acetylcholine receptor signaling pathway (fold enrichment = 15.63, p = 1.01E-03, FDR = 1.64E-01). Expanding to a larger number of genes (CpG p < 5E-04, FDR < 2.25E-01; 1077 CpGs, 662 genes), the most enriched pathway shifted to the muscarinic acetylcholine receptor 1 and 3 signaling pathway (p-value = 5.36E-04, FDR = 4.73E-02). When we stratified by PD status, results were similar. Of the 70 significant CpGs, 63 were detected among both patients and controls and 7 were only associated with OP exposure among patients.ConclusionsThis study finds chronic low-level OP exposure is associated with differential DNA methylation in blood and saliva, both in elderly population controls and PD patients. Our study results suggest that long-term sub-acute OP exposure influences methylation in genes enriched for muscarinic and nicotinic acetylcholine receptor pathways.

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Organophosphate Pesticide Exposure in Pregnancy in Association with Ultrasound and Delivery Measures of Fetal Growth.

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Organophosphate Pesticide Exposure in Pregnancy in Association with Ultrasound and Delivery Measures of Fetal Growth.

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