Urinary 3-phenoxybenzoic acid (3-PBA) levels among pregnant women in Mexico City: Distribution and relationships with child neurodevelopment.

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 (

Factors associated with permanent hearing impairment in infants treated with therapeutic hypothermia.

OBJECTIVE: To define the incidence of hearing impairment, document plasma gentamicin concentrations, and identify factors associated with permanent hearing impairment in infants subjected to therapeutic hypothermia for moderate or severe neonatal encephalopathy. STUDY DESIGN: Data were collected prospectively in a regional center providing therapeutic hypothermia. Cooled infants at ≥ 36 weeks gestation with moderate or severe neonatal encephalopathy were analyzed if a full dataset was available (n = 108), including clinical variables and gentamicin trough levels. Infants with hearing impairment were identified, and survivors were followed up with neurodevelopmental evaluation at age 18 months. Stepwise logistic regression identified factors associated with hearing impairment. RESULTS: Nine infants died, and among the survivors, 10.1% developed a permanent hearing impairment. The trough gentamicin level was above the recommended cutoff of 2 mg/L in 37% of the infants in the entire cohort and in 90% of the infants with hearing impairment. Logistic regression analysis identified high trough gentamicin level, low cord pH, and hypoglycemia (<46.8 mg/dL) in the first postnatal hour as significantly associated with hearing impairment. The need for inotropic support was close to significant (P = .055). CONCLUSION: Hearing impairment was a common finding among cooled infants. Plasma gentamicin levels were commonly >2 mg/L. Based on these findings, we propose changes in gentamicin dosing interval and trough level monitoring to minimize the risk of potentially toxic levels in cooled newborns.

Prenatal urinary phthalate metabolites levels and neurodevelopment in children at two and three years of age.

BACKGROUND: Previous studies suggest that prenatal phthalate exposure affects neurodevelopment and behavior during the first years of life. OBJECTIVES: To evaluate the effect of maternal urinary concentrations of phthalate metabolites during pregnancy on mental and psychomotor development in children 24-36 months of age. METHODS: This analysis was conducted on the first three years of life among a subsample of 136 mother-child pairs from the ELEMENT cohort studies conducted in Mexico City. Maternal urine samples collected during the third trimester of pregnancy were analyzed for 9 phthalate metabolites: Mono-ethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), mono-benzyl phthalate (MBzP), Mono-3-carboxypropyl phthalate (MCPP), and four di-2-ethylhexyl phthalate (DEHP) metabolites [mono-2-ethylhexyl-phthalate (MEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP)]. Among the 136 children, 135 (99.3%) completed the study period. Child neurodevelopment was assessed using mental and psychomotor development indexes (MDI and PDI) from a Bayley (BSID II) test at 24, 30, and 36 months of age. The effect of prenatal phthalate exposure on neurodevelopment was estimated using linear regression models for longitudinal data clustered at the individual level. RESULTS: No significant associations were observed among all children combined, but differential effects by gender were found. Among girls, there was a negative association between MDI and DEHP metabolites MEHP (ß=-2.11 [95% CI: -3.73, -0.49]), MEHHP (ß=-1.89 [95% CI: -3.64, -0.15]), MEOHP (ß=-1.80 [95% CI: -3.58, -0.03]) MECPP (ß=-2.52 [95% CI: -4.44, -0.61]), and ΣDEHP (ß=-3.41 [95% CI: -5.26, -1.55]); there was no significant effect among boys. Male PDI was positively related to MBzP (ß=1.79 [95% CI: 0.14, 3.45]) and MCPP (ß=1.64 [95% CI: 0.15, 3.12]); there was no significant effect on PDI among girls. CONCLUSION: This study demonstrates that sex plays a role of an effect modifier in the association between prenatal phthalate exposure and neurodevelopment.