Carmen Freire1, Esperanza Amaya2, Fernando Gil3, Mario Murcia4, Sabrina LLop4, Maribel Casas5, Martine Vrijheid5, Aitana Lertxundi6, Amaia Irizar7, Guillermo Fernández-Tardón8, Rafael Vicente Castro-Delgado8, Nicolás Olea9, Mariana F Fernández10. 1. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain. 2. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain. 3. Department of Legal Medicine, Toxicology, and Physical Anthropology, School of Medicine, University of Granada, 18071, Granada, Spain. 4. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Epidemiology and Environmental Health Joint Research Unit, FISABIO-Jaume I University-University of Valencia, 46020, Valencia, Spain. 5. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; ISGlobal, Center for Research in Environmental Epidemiology (CREAL), 08036, Barcelona, Spain; Universitat Pompeu Fabra, 08005, Barcelona, Spain. 6. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; BIODONOSTIA Health Research Institute, 20014, San Sebastián, Spain; Department of Preventive Medicine and Public Health, University of the Basque Country (UPV/EHU), 48940, Leioa, Bizkaia, Spain. 7. BIODONOSTIA Health Research Institute, 20014, San Sebastián, Spain. 8. CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; IUOPA, Department of Preventive Medicine and Public Health, School of Medicine, University of Oviedo, 33003, Oviedo, Spain. 9. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Department of Radiology, School of Medicine, and Center for Biomedical Research, University of Granada, 18071, Granada, Spain. Electronic address: nolea@ugr.es. 10. Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), 18012, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Spain; Department of Radiology, School of Medicine, and Center for Biomedical Research, University of Granada, 18071, Granada, Spain.
Abstract
OBJECTIVE: To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain. METHODS: Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated. RESULTS: Elevated placental Cd levels (>5.79 vs. <3.30 ng/g) were associated with reduced birth weight (-111.8 g, 95%CI = -215.6; -8.06, p-trend = 0.01) and length (-0.62 cm, 95%CI = -1.20; -0.04, p-trend = 0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI = 1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI = 0.78; 0.96) of preterm delivery in males (Pinteraction = 0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (-0.49 cm, 95%CI = -1.00; 0.03) in females (Pinteraction = 0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI = 0.01; 0.07) in the global sample and in head circumference (0.05 cm, 95%CI = -0.01; 0.10) in females (Pinteraction = 0.03). Elevated Cr levels (>99.6 vs. <56.1 ng/g) were associated with reduced birth length (-0.68 cm, 95%CI = -1.33; -0.04, p-trend = 0.02) and slightly increased gestational age (0.35 weeks, 95%CI = -0.07; 0.77, p-trend = 0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome. CONCLUSIONS: Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.
OBJECTIVE: To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain. METHODS:Metal concentrations were measured in placenta tissue samples randomly selected from five INMA cohorts. Data on birth outcomes were obtained from medical records. Associations were assessed in a sub-sample of 327 mother-infant pairs by regression models adjusted for confounding factors and for all metals simultaneously. Effect modification by sex was also evaluated. RESULTS: Elevated placental Cd levels (>5.79 vs. <3.30 ng/g) were associated with reduced birth weight (-111.8 g, 95%CI = -215.6; -8.06, p-trend = 0.01) and length (-0.62 cm, 95%CI = -1.20; -0.04, p-trend = 0.02), while a 10% increase in Cd was associated with 1.21-fold increased odds (95%CI = 1.01; 1.43) of LBW in the global sample but with 14% lower odds (95%CI = 0.78; 0.96) of preterm delivery in males (Pinteraction = 0.10). Detected (vs. undetected) Hg was associated with reduced head circumference (-0.49 cm, 95%CI = -1.00; 0.03) in females (Pinteraction = 0.03). A 10% increase in placental Mn was associated with slight increases in gestational age (0.04 weeks, 95%CI = 0.01; 0.07) in the global sample and in head circumference (0.05 cm, 95%CI = -0.01; 0.10) in females (Pinteraction = 0.03). Elevated Cr levels (>99.6 vs. <56.1 ng/g) were associated with reduced birth length (-0.68 cm, 95%CI = -1.33; -0.04, p-trend = 0.02) and slightly increased gestational age (0.35 weeks, 95%CI = -0.07; 0.77, p-trend = 0.08) in the global sample. As and Pb were detected in few placentas (27% and 13%, respectively) and were not associated with any studied birth outcome. CONCLUSIONS: Data suggest that in utero exposure to Cd, Hg, and Cr could adversely affect fetal growth, whereas Mn and Cr appear to have a positive effect on gestational age. Given the relatively small number of subjects, sex-specific associations should be interpreted with caution.
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