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BACKGROUND: In recent years, pyrethroid pesticide use has increased in Mexico, the United States, and elsewhere, resulting in extensive human exposure. There is growing concern that pregnant women may be a particularly vulnerable population, as in utero fetal exposure during critical periods of development could adversely affect long-term neurobehavioral function. METHODS: We measured maternal urinary 3-phenoxybenzoic acid (3-PBA) concentrations during the third trimester of pregnancy as a measure of in utero pyrethroid exposure to the fetus among participants in an established Mexico City birth cohort (n=187). In a subset of mothers, we measured 3-PBA during the first, second, and third trimester (n=21) to assess variability across pregnancy. We examined associations between third trimester 3-PBA concentrations and children's scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) from the Bayley Scales for Infant Development (BSID-IIS) at 24 and 36 months of age. RESULTS: 3-PBA was detected in 46% of all urine samples, with similar detection rates and geometric mean concentrations across pregnancy among the 21 participants who provided repeat samples. Participants in the medium and high 3-PBA categories (≥LOD) had lower MDI scores at 24 months compared to those in the low 3-PBA category (

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OBJECTIVE: To evaluate the association of second-hand smoke exposure of pregnant mothers using urine cotinine with the neurodevelopment of their children at 18 months of age in the mother-child cohort in Crete (Rhea Study). STUDY DESIGN: Selected participants were Greek mothers with singleton pregnancies, had never smoked, and had available urine cotinine measurements in pregnancy, and their children for whom a neurodevelopmental assessment was completed. We performed face-to-face interviews twice during pregnancy and postnatally, and assessed children's neurodevelopment at 18 months of age using the Bayley Scales of Infant and Toddler Development, Third Edition. We used linear regression and generalized additive models. RESULTS: Of 599 mothers, 175 (29%) met the inclusion criteria. Maternal urine cotinine levels were low (mean: 10.3 ng/mL, SD: 11.7 ng/mL). Reported passive smoking from different sources was strongly associated with urine cotinine levels. A negative association was observed between cotinine levels in pregnancy and child's gross motor function (beta = -3.22 per 10 ng/mL, 95% CI -5.09 to -1.34) after adjusting for factors potentially associated with neurodevelopment; results were similar in both sexes. A negative association was also observed for cognitive and receptive communication scales but the effect was small and not statistically significant. CONCLUSIONS: Maternal exposure during pregnancy to second-hand smoke measured through urine cotinine was associated with a decrease in gross motor function among 18-month-old children, even at low levels of exposure.

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INTRODUCTION: Fetal programming by different insults results in low birth weight and reduction in nephron number increasing the risk for adult development of cardiovascular and renal diseases. Maternal smoking is an important modifiable adverse fetal exposure worldwide and leads to a decrease in the offspring's birth weight. Thus far, the specific adverse fetal smoking exposures and mechanisms underlying these associations on renal development and functional disorder are unclear. METHODS: The present study investigates, in adult male rats, the effect of smoking exposure (Sk) in uteri on blood pressure (BP) by an indirect tail-cuff method using an electrosphygmomanometer, and its association with nephron structure by stereological estimation, immunohistochemical and histological techniques, in parallel with kidney function creatinine and lithium clearance. RESULTS: The current study showed in a 16-week old Sk offspring enhanced arterial blood pressure associated with, reduced urinary sodium excretion and higher TGF-ß1 glomerular expression. Sk glomeruli also presented an upregulated collagen and fibronectin deposition intrinsically related to fibrotic process as compared to age-matched control group. CONCLUSION: Here, we demonstrate that fetal-programmed Sk offspring present pronounced glomerular TGF-ß1 and fibrotic marker expression that may, subsequently, promote a glomerular epithelial-mesenchymal transition activated process in an Sk offspring. Although the precise mechanism responsible for the subsequently renal morphological and functional response in Sk offspring is incompletely known, the current data suggest that changes in renal function are conducive to excess sodium tubule reabsorption that is associated with enhanced TGF-ß1, fibronectin and collagen deposition, intrinsically related to fibrotic process, might potentiate the programming of adult hypertension.

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