The Study On The Association Between Gestational Weight Gain And Adverse Outcomes In Twin Pregnancies And The Value Of Ultrasound In Early Diagnosis

Background and objective:As the increasing age of pregnant women and the popularization and application of assisted reproductive technology,the twin pregnancy rate is showing an upward trend.Compared with singleton pregnancy,the fetal growth environment in twin pregnancy is more complicated,and the risk of adverse outcomes such as premature delivery and low birth weight is higher.Gestational weight gain（GWG）is not only an important indicator to evaluate a pregnant woman’s and fetal nutritional status,but also a vital factor in promoting the health of the mother and fetus.Previous studies had shown that abnormal weight gain during pregnancy could increase the risk of pregnancy complications and adverse pregnancy outcomes,and is closely related to the future health of the mother and the fetus.However,currently only the Institute of Medicine（IOM）has formulated the recommended guidelines for GWG in twin pregnancy.There have been relevant research reports in China in recent years,but there is still insufficient evidence and general consensus has not been formed.Selective fetal growth restriction（sFGR）is recognized as a common and severe complication of monochorionic（MC）twin pregnancy,resulting in intrauterine fetal death,neurological impairment,and neonatal death.At present,the second trimester ultrasound is used for early diagnosis of sFGR in clinical practice at home and abroad,but its diagnostic value is still controversial.Therefore,the main purposes of this research are as follows:（1）To clarify the relationship between gestational weight gain and pregnancy complications[gestational diabetes mellitus（GDM）,hypertensive disorders of pregnancy（HDP）,etc.]and adverse pregnancy outcomes[preterm birth,postpartum hemorrhage,low Low birth weight（LBW）,etc.]in twin pregnant women.（2）To evaluate the early diagnostic value of sFGR by the second trimester ultrasound,and compare the diagnostic value of ultrasound indicators related to sFGR in different regions.Methods:This study is divided into two chapters.In Chapter 1,a prospective cohort study which included twin pregnant women who gave birth at Qingdao Women and Children’s Hospital and met the inclusion criteria was conducted from September 2018 to December2020.The questionnaire and the maternal and children’s health handbook were used for data collection,including general demographic characteristics,pregnancy information,lifestyle habits.The electronic medical records was used to collect pregnancy outcome information.According to the evaluation criteria of P₂₅-P₇₅and IOM,GWG was divided into three groups:insufficient,normal,and excessive.After adjusting for confounding factors,such as maternal age,pre-pregnancy BMI,chorionicity,multivariate logistic regression was used to analyze the associaton between GWG and GDM,HDP,preterm delivery,postpartum hemorrhage,LBW and other outcomes.Odds ratio（OR）and 95%confidence interval（CI）were used to determine the size of the association.Then,the further stratified analysis was carried out based on the low weight,normal weight,overweight and obesity before pregnancy.In Chapter 2,the subjects were from the twin pregnant women who were diagnosed with MC between August 2019 and December 2020 among the Chapter 1 subjects.From16 to 24 weeks of pregnancy,ultrasound is used to assess the growth status of twins and early diagnosis of sFGR.At the same time,the sFGR early ultrasound diagnosis was also performed on MC twin pregnant women who were treated at Leiden University Medical Center in the Netherlands from January 2008 to December 2013.The receiver operator characteristic curve（ROC）was used to compare and analyze the second trimester ultrasound diagnosis results and the incidence of postpartum sFGR,calculate the sensitivity and specificity of each ultrasound index.The area under the ROC curve（AUC）was used to evaluate the early diagnosis value of sFGR by the second trimester ultrasound,and compare the early diagnosis value of ultrasound in the two places.Results:1.In the study of the association between gestational weight gain and the adverse outcomes of twin pregnancy（Chapter 1）:（1）A total of 1,014 twin pregnant women were included in this study.The incidence of GDM,HDP was 36.00%,12.62%,respectively.According to the P₂₅-P₇₅criterion,in all twin pregnant women,the risk of GDM in those with insufficient GWG was 1.41times that of pregnant women with normal GWG（a OR,1.41;95%CI,1.01-1.95）.Among pregnant women who were overweight before pregnancy,excessive GWG was associated with increased risk of HDP（a OR,2.55;95%CI,1.20-5.43）.According to the IOM criterion,insufficient GWG was an independent risk factor for GDM,among the pregnant women with low weight,normal weight and overweight.Among low-weight pregnant women,the risk of HDP for excessive GWG was 1.33 times higher than that of normal GWG（a OR,2.33;95%CI,1.47-3.10）.（2）The incidence of preterm birth and postpartum hemorrhage were 41.52%and27.91%respectively.Referred to P₂₅-P₇₅criterion,insufficient GWG increased the risk of preterm birth（a OR,2.09;95%CI,1.52-2.89）,but it was related to the reduced risk of postpartum hemorrhage,and its risk was reduced by 36%（a OR,0.64;95%CI,0.44-0.93）.Referred to the IOM standard,among the pregnant women with with low,normal weight and obesity,insufficient weight gain was associated with increased risk of preterm birth.（3）The incidence of low birth weight（LBW）in large and small fetuses was 31.26%and 56.71%respectively.The insufficient weight gain during pregnancy was associated with increased the risk of twins’LBW.In addition,according to the P₂₅-P₇₅standard,excessive GWG was associated with reduced the risk of LBW.2.In the study of the early diagnostic value of selective fetal growth restriction by the second trimester ultrasound（Chapter 2）:（1）This study included 93 cases of MC pregnant women in Qingdao Women and Children’s Hospital,and 34（35.65%）cases with sFGR.The sensitivity and specificity of ultrasound diagnosis of sFGR were 67.65%and 79.66%,and the positive predictive value and negative predictive value were 65.71%and 81.03%,respectively.（2）Leiden University Medical Center enrolled 280 cases of MC pregnant women,of which 118（42.14%）cases complicated by sFGR.The sensitivity and specificity of ultrasound diagnosis of sFGR in the second trimester in this center were 75.42%and89.51%,and the positive predictive value and negative predictive value are 83.96%and83.33%,respectively.（3）Among the ultrasound indicators in the second trimester,estimated fetal weight（EFW）discordance obtained the highest diagnostic value in the diagnosis of sFGR,and its AUC was 0.77（95%CI,0.66-0.88）at Qingdao Women and Children’s Hospital.At Leiden University Medical Center,the AUC of discordant EFW was 0.83（95%CI,0.77-0.88）.（4）Further analysis of the combined indicators for the diagnostic value of sFGR found that the use of discordant abdominal circumferences combined with discordant fetal weight for MC pregnant women in Qingdao achieved the highest diagnostic value（AUC,0.78;95%CI,0.68-0.89）.In Leiden,the optimal diagnostic effectiveness for sFGR could be obtained by combining twins’abdominal circumferences discordance,estimated fetal weight discordance,and the umbilical blood flow of the small fetus（AUC,0.88;95%CI,0.84-0.93）.Conclusion:The weight gain during pregnancy of twin pregnant women is associated with the risk of pregnancy complications（GDM,HDP）and adverse pregnancy outcomes（premature birth,low birth weight）.Insufficient gestational weight gain is associated with an increased risk of GDM,premature birth,and low birth weight,while excessive weight gain increases the risk of HDP.Second trimester ultrasound possesses a good early diagnostic value for selective fetal growth restriction.sFGR could be diagnosed more accurately through the combination of discordant abdominal circumference,discordant estimated fetal weight,and umbilical blood flow of small fetus.Therefore,the weight management of twin pregnant women should be strengthened to keep it within an appropriate range,and routine ultrasound monitoring should be performed from the second trimester to regularly assess the growth status of twins,so as to improve the maternal and infant outcome.