Risk Factors And Methylation Differences In Selective Fetal Growth Restriction

Objective:Recently,thanks to the emancipation of China's family planning policy and in addition to development of assisted reproductive technology(ART),the twining rate has been rising,as result the adverse pregnancy outcomes have gradually arouse attention.Further,selective intrauterine growth retardation(sIUGR)is a common but complicated complication of monochorionic twins.Thus,in this article we aim to explore the antenatal influencing factors of sIUGR and neonatal outcomes,as well as the correlation between umbilical cord blood genomic methylation level and birth weight of newborn,and then to find the risk factors of sIUGR,and to explain the possible pathogenesis of this disease,in order to provide clues and theoretical basis to preventing this disease and guiding clinical.Methods: Recruiting monozygotic twins who delivered at obstetrics and gynecology department in Dalian Municipal Women and Children's Medical Center from September 2016 to November 2018.Registering their information,which were included in the hospital database,then proceeding retrospective analysis.During the period,450 pairs of twins were delivered,of which 10 pairs with sIUGR enrolled as the study group,and 34 pairs with normal weight were enrolled as the control group.After obtaining the informed consent of the study subjects,5ml of the umbilical vein blood was taken after vaginal or cesarean delivery,which placed in a tube with EDTA stored at-80°C.Using TIANamp Blood DNA kit(centrifugal column)extracted DNA of leukocytes from cord blood samples,then using MethylFlashTM methylation DNA quantification kit(colorimetric method)measured the whole genome methylation by reading the absorbance at a wavelength of 450 nm in microplate reader.Data analysis was used SPSS 22.0 statistical software.Results: 1.Comparison of general information between the two groups of maternal.The gestational age in the sIUGR group were smaller than the control group(P<0.05).There was no statistically significant difference in maternal age,parity and conceptive style.2.Comparison of maternal pregnancy complications and comorbidities between the two groups.The incidence of hypertensive disorders complicating pregnancy and placental cord abnormalities in the sIUGR group were higher than the control group(P<0.05).There was no statistically significant difference in the incidence of diabetes,thyroid dysfunction,placenta previa,premature rupture of membrane,postpartum hemorrhage,and anemia during pregnancy.3.Comparison of general information between the two groups of newborns.The weight,large fetus body length in the sIUGR group was significantly smaller than the control group.And the difference in the asphyxia rate,the body weight between the two fetuses was higher than the control group(P<0.05).There was no statistically significant different gender between the two groups.4.Comparison of cord methylation levels between the two groups.The whole genome methylation level of leukocytes in neonatal cord blood was positively relative with birth weight.The methylation level of small fetus in sIUGR group was significantly lower than the control group.The difference of methylation level between the two fetuses was greater than that in the control group(P<0.05).The methylation levels of the large fetuses were similar,and the difference was not statistically significant.Conclusion: The sIUGR have poor prognosis and high mortality.The maternal hypertensive disorders complicating pregnancy and the abnormality of placental cord are related to the occurrence of sIUGR.Fetus could be affected by affecting epigenetics in different intrauterine environment,the mechanism may be related to the degree of DNA methylation,leading to the selective intrauterine growth retardation.Therefore,all pregnant women should be screened for high risk factors of sIUGR through a complete medical history,closely monitor to detect sIUGR as early as possible,then choose appropriate prenatal interventions and terminate the pregnancy.