Maternal Hair Metabolomics Of Fgr Across Pre-conception To Third Trimester

Background:Fetal growth restriction(FGR)is the condition in which the fetus does not reach its genetic potential.FGR will not only increase perinatal morbidity and mortality,for example,premature infants,hypoglycemia,hypothermia,but is also associated with many long-term complications,such as cardiovascular disease and insulin resistance syndrome.With the improvement of living standards,fetal birth weight has been increasing year by year.The proportion of FGR selected out is far less than the criteria—10%,indicating the current birth weight table for FGR is no longer applicable.Thus,it is necessary to establish a new growth curve and birth weight table for FGR.Metabolomics,as an emerging omics,is attracting more and more attention and is applied into multiple disciplines.The hair metabolomics is particularly prominent,which can reflect not only the internal metabolic changes,but also the external exposure.However,there are few studies of hair metabolomics of FGR.The published studies of hair metabolomics ofFGR were with small sample sizes,which did not explore the metabolic changes of FGR at pre-conception and first trimester of pregnancy.Therefore,using a large cohort to study hair metabolomics of FGR across pre-conception to third trimester could help to better understand fetal growth restriction.Objective:To establish a new growth curve and birth weight table of FGR for Chongqing;To study the longitudinal metabolic changes of fetal growth restriction across pre-conception to third trimester using maternal hairs of CLIMB cohort.Methods:We collected all the neonatal birth weight data in a total of 120 hospitals in Chongqing from January 2014 to October 2017.After normal transformation using LMS method,the new growth curve was drawn,and thus the 10 th centile birth weights at different gestational weeks were determined.According to the new birth weight chart,FGR was selected out from CLIMB cohort which enrolled 1500 participates for research.The hair samples collected at 32-34 gestational weeks of whole cohort were used for GC-MS analysis to explore the longitudinal metabolic changes.Results:The birth weight data of a total of 348454 fetuses were collected in Chongqing area.We successfully established a fetal growth curve suitablefor Chongqing and new 10 th centile birth weight chart at different gestational weeks.According to the new chart,we selected out 96 cases of fetal growth restriction with hair samples,while 927 samples were included as non-FGR group.Finally,a total of 45 significantly different metabolites were found,which were mainly amino acids,fatty acids and organic acids.Besides,the differences between two group were mainly concentrated in the third trimester.The major pathways in which different metabolites participated is amino acid-related pathway.Conclusion:We established a reliable fetal growth curve and birth weight chart of FGR for Chongqing,which provided a new basis for diagnosis of FGR in the future.The results of this study provide better insights into the longitudinal changes in the hair metabolome across pre-conception to late pregnancy.In addition,our results highlight the potential of the maternal hair metabolomics in finding biomarkers of pregnancy complications.