Research | Children’s Health Effect of Arsenic Exposure during Pregnancy on Infant Development at 7 Months in Rural Matlab, Bangladesh Fahmida Tofail,1 Marie Vahter,2 Jena D. Hamadani,1 Barbro Nermell,2 Syed N. Huda,3 Mohammad Yunus,1 Mahfuzar Rahman,1,4 and Sally M. Grantham-McGregor 5 1Child Development Unit, Clinical Sciences Division and Public Health Sciences Division, International Center for Diarrhoeal Disease Research, Dhaka, Bangladesh; 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 3Institute of Nutrition and Food Science, University of Dhaka, Dhaka, Bangladesh; 4Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA; 5Centre for International Health and Development Institute of Child Health, University College London, London, United Kingdom Bdnuorgkca o Bjectiv : Exposure to arsenic-contaminated drinking water during pregnancy is associated with low birth weight and fetal loss, and there is concern that the infants’ development may be affected. : We assessed the effects of in utero arsenic exposure during pregnancy on infants’ prob- lem-solving ability and motor development. Msdohte : We conducted a large population-based study of nutritional supplementation with 4,436 pregnant women in Matlab, Bangladesh, an area of high-arsenic–contaminated tube wells. We meas- ured arsenic concentration in spot urine specimens at 8 and 30 weeks of pregnancy. We assessed a subsample of 1,799 infants, born to these mothers, at 7 months of age on two problem-solving tests (PSTs), the motor scale of the Bayley Scales of Infant Development–II, and behavior ratings. r esult : Arsenic concentrations in maternal urine were high, with a median (interquartile range) of 81 µg/L (37–207 µg/L) at 8 weeks of gestation and of 84 µg/L (42–230 µg/L) at 30 weeks. Arsenic exposure was related to many poor socioeconomic conditions that also correlated with child devel- opment measures. Multiple regressions of children’s motor and PST scores and behavior ratings, controlling for socioeconomic background variables, age, and sex, showed no significant effect of urinary arsenic concentration on any developmental outcome. c onclusi : We detected no significant effect of arsenic exposure during pregnancy on infant development. However, it is possible that other effects are as yet unmeasured or that effects will become apparent at a later age. k ey words : Bangladesh cognitive function, infants, motor development, problem-solving tests, uri- nary arsenic. Environ Health Perspect 117:288–293 (2009). doi:10.1289/ehp.11670 available via http://dx.doi.org/ [Online 24 October 2008] Arsenic is a widely distributed environmental pollutant with known carcinogenic and neu- rotoxicant effects [World Health Organization (WHO) 2001]. More than 100 million people worldwide have been estimated to be chroni- cally exposed to drinking water containing high arsenic levels (Alaerts et al. 2001; National Research Council 2001). In Bangladesh, a nationwide survey initiated in 1998 indicated that about 35 million people were exposed to > 50 µg/L arsenic, which is the drinking water standard in Bangladesh, whereas 57 mil- lion had water exceeding the WHO guideline value of 10 µg/L (British Geological Survey 2001). Studies in school-age children have reported that arsenic exposure due to living near smelters in Mexico (Calderón et al. 2001; Rosado et al. 2007) and the United Sates (Wright et al. 2006) or drinking contaminated water in Taiwan (Tsai et al. 2003) and India (von Ehrenstein et al. 2007) is associated with deficits in children’s cognitive function. Two recent studies in Bangladesh in children 6 and 10 years of age (Wasserman et al. 2004, 2007) showed that arsenic concentration in their drinking water was related to deficits in global and performance IQ that were larger at 10 than at 6 years of age. We are unaware of any prospective study examining the effect of exposure in pregnancy 288 on offspring development. During pregnancy, transplacental transfer of arsenic occurs both in animals (Golub et al. 1998) and in humans (Concha et al. 1998). In animals, a high dose of arsenic is associated with detrimen- tal effects on the developing embryo (Golub et al. 1998; National Research Council 1999; Wlodarczyk et al. 1996). In humans, expo- sure to high arsenic levels in drinking water is associated with reduction in birth weight (Hopenhayn et al. 2003; Huyck et al. 2007) and increase in fetal loss (Ahmad et al. 2001; Rahman et al. 2007). Considering the above, we hypothesized that arsenic exposure during pregnancy would be neurotoxic to the devel- oping brain and would lead to behavioral changes in the offspring. We conducted a large community-based randomized trial of the effects of food and micronutrient supplementation in pregnant women [Maternal and Infant Nutritional Intervention at Matlab (MINIMat) study] on birth outcomes and the development of their children in Matlab, a rural area of Bangladesh. We previously reported that in infants of undernourished mothers, food and micronutrient supplements added small ben- efits to their development at 7 months of age (Tofail et al. 2008). In the study area, 63% of all functioning tube wells were found to have > 50 µg/L arsenic in the water (Vahter et al. 2006). We obtained information on concurrent arsenic exposure of these women by measurements of arsenic in their urine col- lected twice during pregnancy (Vahter et al. 2006). The aim of this study was to exam- ine the relationship between prenatal arsenic exposure and infants’ cognitive and motor development at 7 months of age. Materials and Methods Study area. The study area is in Matlab, a subdistrict of Chandpur, and is the field site of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B). It includes 142 villages covering a population of 220,000. It is located in the delta formed by the Meghna and the Ganges Rivers that lies in the east-central plain of Bangladesh, 53 km southeast of Dhaka. It is a poor rural area, and the main economic activities are farming, fishing, trading, and crafts. In this area, 95% of the population use tube wells for drink- ing water, and > 60% of the wells have arse- nic levels > 50 µg/L (Rahman et al. 2006). ICDDR,B has maintained a Health and Demographic Surveillance System (HDSS) in the area to collect vital demographic and health information since 1966. MINIMat study. We identified preg- nant women for the MINIMat study using the HDSS, in which all homes in the area were visited monthly and women were asked about their menstruation. If they reported amenorrhea at the time of a home visit and pregnancy was confirmed by urine tests Address correspondence to S. Grantham-McGregor, CIHD, Institute of Child Health, 30 Guilford St., London WC1N 1EH UK. Telephone: 44-0-20- 7242-9789. Fax: 44-0-20-7831-0488. E-mail: sal- lymcgregor@yahoo.com We thank P. Willatts for assistance with cognitive tests, the testers, supervisors, and participants. The work was supported by the International Centre for Diarrheal Disease Research, Bangladesh; United Nations Children’s Fund; Swedish International Development Cooperation; U.K. Medical Research Council; Swedish Research Council; U.K. Department for International Development; Global Health Research Fund, Japan; Child Health and Nutrition Research Initiative; and Uppsala University. financial interests. The authors declare they have no competing Received 7 May 2008; accepted 24 October 2008. ovlume 117 | number 2 | February 2009 • Environmental Health Perspectives