Effects Of Prenatal Exposure To Polybrominated Diphenyl Ethers(PBDEs)on Infant Birth Outcomes And Children's Neurodevelopment

Objective:Polybrominated Diphenyl Ethers?PBDEs?are brominated flame retardants?BFRs?that are widely used in polymer-based commercial applications,furniture and infant products.PBDEs have the capacity to pass through the placental barrier and the blood-brain barrier,and into the fetal blood stream,pose health risks of neurological development to fetuses and neonates.Prenatal exposure to PBDEs is a major pathway of PBDEs exposure in infants.This study aim to determine the prenatal PBDEs exposure in a birth cohort in the south coast area of Laizhou Wan?Bay?,one of the major BFRs production areas in China,and to analyze the potential association between PBDEs exposure and fetal development and children's developmental quotients?DQs?at 12 and 24 months of age based on the Gesell Developmental Schedules,and to evaluate the effects and the mechanisms.Methods:From September 2010 to December 2013,a total of 773 pregnant women who delivered their babies in the hospital near the PBDEs production area?the south coast area of Laizhou Wan,Shandong Province,China?were recruited in our study.Informed consent was obtained and interviews through questionnaire were conducted with the women.Maternal and umbilical cord blood samples were obtained,and the information on the current delivery and birth outcomes was retrieved from medical records.?1?Eight PBDE congeners?BDE-28,-47,-85,-99,-100,-153,-154and-183?were measured in 218 maternal serums and 223 cord serums.?2?Children's developmental quotients?DQs?in motor,adaptive,la nguage,and social domains based on the Gesell Developmental Schedules?Gesell?was followed when they were12 and 24 months old,and mothers'IQ was determined by Raven's Standard Progressive Matrices?SPM?.?3?We also examined whether thyroid hormones?TSH,T₃,FT₃,T₄,and FT₄?in cord serum were associated with PBDEs exposures or birth outcomes,and methylation specific polymerase chain reaction?MSP?was adopted to analyze the methylation or detection status of BDNF gene,to discuss whether BDNF in cord serum was related with PBDEs exposures or children's neurodevelopment.Results:?1?The total maternal serum concentration of all of the PBDE congeners?ranges?was 22.91?3.07-983.63?ng/g lipids.The detection rate of BDE-153 was 94.50%.The total level of all of the PBDE congeners in cord serum?ranges?was 24.99?9.43-2459.46?ng/g lipids.The detection rate of BDE-47 and BDE-99 was over 90%in all samples.The levels of exposure to PBDEs in maternal and umbilical cord serums in the present study were higher than those of similar studies conducted in the general population in China,Asia and Europe,but lower than those in general population in North America and some cities in China such as Guiyu and Taizhou?high PBDEs exposure because of e-waste recycling?.?2?We found that maternal LgBDE-28 and LgBDE-100 were negatively associated with birth length.A negative association was found between LgBDE-28 and birth weight among male infants.We also found that cord LgBDE-47 and LgBDE-99 were positively associated with infant head circumference,and cord BDE-47,-99,-100 positively associated with gestation age.At 24 months of age,a 10-fold increase in BDE-99 levels was associated with a 2.16-point decrease in language domain DQs and a 10-fold increase in BDE-47 levels was associated with a 1.89-point decrease in social domain DQs.?3?A 10-fold increase in cord serum BDE-99 and?₄ PBDEs?the sum of BDEs 47,99,100,and 153?concentrations was associated with a 0.43?g/dl and 0.35?g/dl increase in total thyroxin levels?T₄?,respectively.We found that cord PBDEs exposure?BDE-47,-99?was positively associated with BDNF CpG island chip.However,we found that cord PBDEs exposurwe was positively associated with BDNF levels,and there was no relationship between BDNF gene methylation and BDNF levels.Conclusion:The levels of exposure to PBDEs in pregnant women and newborns in our study area,the south coast area of Laizhou Wan,Shandong Province,China were relatively higher than that of the general population in other studies in China,Asia and Europe,but lower than that of general population in north America and some cities in China such as Guiyu and Taizhou?high PBDEs exposure because of e-waste recycling?.PBDEs are likely to be thyroid disruptors in humans,and negative association between prenatal PBDEs?BDE-28 and-100?exposure and infant birth outcome?birth length and birth weight?was found,and prenatal exposure to PBDEs?BDE-47 and BDE-99?could adversely affect child's neurodevelopment?language and social development?.We have not found the important role of BDNF gene expression in the neurotoxic mechanism of PBDEs.Further epidemiological studies with larger sample sizes are required to evaluate the relationship between PBDE exposures and birth outcomes,children's neurodevelopment,and to illustrate the mechanistic pathways underlying exposure to PBDEs andchildren's development.