Neurodevelopmental performance among school age children in rural Guatemala is associated with prenatal and postnatal exposure to carbon monoxide, a marker for exposure to woodsmokeBackgroundMaterials and methodsParticipants and recruitmentCO exposureNeurodevelopmental assessmentsMaternal interviewsStatistical analysesResultsPopulation characteristicsCO exposuresNeuropsychological scoresMaternal second trimester and infant CO exposuresDiscussionConclusionsConflict of interest declarationAcknowledgementsSupplementary dataReferencesNeurodevelopmental performance among school age children in ruralGuatemala is associated with prenatal and postnatal exposure to carbonmonoxide, a marker for exposure to woodsmokeLinda Dix-Coopera, Brenda Eskenazib, Carolina Romeroc, John Balmesa,d, Kirk R. Smitha,*aDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360, USAbCenter for Environmental Research and Children’s Health (CERCH), School of Public Health, University of California, Berkeley, CA, USAcCentro de Estudios en Salud Universidad Del Valle, GuatemaladDivision of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, CA, USA1. BackgroundWood and other forms of biomass provide readily available andoften free cooking and heating fuel for millions of developing worldhouseholds. Woodsmoke, however, contains thousands of chemi-cals, in the form of incomplete combustion products, many ofwhich are known to be hazards to health (Naeher et al., 2007).Chronic, elevated biomass smoke exposure during pregnancy hasbeen associated with low birth weight (Boy et al., 2002; Mishraet al., 2004; Pope et al., 2010; Siddiqui et al., 2008; Thompson et al.,2011b). Carbon monoxide (CO), an indicator of woodsmokeexposure and the largest constituent of incomplete combustion,is a neurotoxicant at high exposure levels among adults (Hsiaoet al., 2004; Thom et al., 1995) and children (Kim and Coe, 1987;Klees et al., 1985). Initial symptoms of CO exposure among adultsat levels equivalent to 5–20% carboxyhemoglobin (COHb) includeheadache, fatigue, malaise, and difficulty concentrating (EPA,2010; Hsiao et al., 2004; Thom et al., 1995; Weaver, 1999). Thedeveloping nervous system is especially vulnerable to environ-mental insults (Rice and Barone, 2000).NeuroToxicology 33 (2012) 246–254A R T I C L E I N F OArticle history:Received 23 March 2011Accepted 15 September 2011Available online 24 September 2011Keywords:Household air pollutionIndoor air pollutionCookstovePrenatal exposuresIn uteroMotor skillsRESPIRE studyA B S T R A C TWe investigated whether early life chronic exposure to woodsmoke, using personal passive 48-h carbonmonoxide (CO) as an indicator, is associated with children’s neurodevelopmental and behavioralperformance. CO measures were collected every 3 months from 2002 to 2005 among mother–child dyadsduring the Randomized Exposure Study of Pollution Indoors and Respiratory Effects (RESPIRE) stoveintervention trial in San Marcos, Guatemala. From March to June, 2010, study children of age 6–7 years,performed a follow-up non-verbal, culturally adapted neurodevelopmental assessment. We found inverseassociations between CO exposure of pregnant mothers during their 3rd trimesters(m = 3.8 ppm  3.0 ppm; range: 0.6–12.5 ppm) and child neuropsychological performance. Scores on 4 outof 11 neuropsychological tests were significantly associated with mothers’ 3rd trimester CO exposures,including visuo-spatial integration (p < 0.05), short-term memory recall (p < 0.05), long-term memory recall(p < 0.05), and fine motor performance (p < 0.01) measured using the Bender Gestalt-II’s Copy, ImmediateRecall, and an adapted version of a Delayed Recall Figures drawing, and the Reitan-Indiana’s Finger TappingTests, respectively. These 4 significant finding persisted with adjustment for child sex, age, visual acuity, andhousehold assets (socio-economic status). Summary performance scores were also significantly associated withmaternal 3rd trimester CO when adjusted for these covariates. Other variables accounting for variance but wereexcluded in our final multiple regression models included the following: HOME environment stimulation score,child examiner, WHO height-for-age percentile, and age that the infant stopped breastfeeding. This seems to bethe first study on woodsmoke exposure and neurodevelopment, and the first longitudinal birth cohort study onchronic early life CO exposures, determined by high quality measures of mothers’ and infants’ personal COexposures, and using well-established, reliable child neuropsychological tests. Further research is needed toreplicate our results and inform future interventions and air quality standards for woodsmoke and CO.ß 2011 Elsevier Inc. All rights reserved.Abbreviations: Bender Gestalt-II, Bender visual-motor Gestalt test, second edition;CI, confidence interval; CO, carbon monoxide; COHb, carboxyhemoglobin; CRECER,Chronic Respiratory Effects of Early Childhood Exposure to Respirable ParticulateMatter; eCO, exhaled breath CO; ETS, environmental tobacco smoke; HOME, HomeObservation for Measurement of the Environment; RESPIRE, Randomized ExposureStudy of Pollution Indoors and Respiratory Effects; WISC-IV Spanish, WechslerIntelligence Scale for Children-Fourth Edition in Spanish.* Corresponding author. Tel.: +1 510 643 0793.E-mail address: [email protected] (K.R. Smith).Contents lists available at SciVerse ScienceDirectNeuroToxicology0161-813X/$ – see front matter ß 2011 Elsevier Inc. All rights reserved.doi:10.1016/j.neuro.2011.09.004An oxygen antagonist, CO binds to hemoglobin in red bloodcells with an affinity 250 times greater than that of oxygen to forma hypoxia-inducing carboxyhemoglobin (COHb) complex that canalso impair the release of oxygen from oxyhemoglobin (Hb-O2) infetal blood (Cramer, 1982). CO has the ability to cross the bloodbrain barrier and impair neuronal function, membrane metabo-lism, and anaerobic energy metabolism (Kondziella et al., 2009),targeting the globus pallidus (a subcortical structure involved inmotor and postural control) (Alehan et al., 2007; Hsiao et al., 2004).In utero CO exposure may interrupt sensitive oxygen-dependentneurodevelopmental processes such as myelination (Shprecherand Mehta, 2010), neural packing (Lin et al., 2009), and neuronalmigration (Knipp and Bicker, 2009). Following chronic