A Prospective Cohort Study On The Relationship Between Gestational Metabolic Disorders And Adverse Pregnancy Outcomes

Background:Gestational metabolic disorders(GMD)refers to a group of diseases closely related to metabolic abnormalities in women during pregnancy,including gestational diabetes mellitus(GDM),gestational hypertension(GHTN)or preeclampsia(PE),gestational overweight or obesity,and gestational metabolic syndrome.All diseases in GMD are common complications during pregnancy,and they still have a high incidence rate worldwide.GMD not only has a significant impact on the occurrence of adverse pregnancy outcomes,but also has a far-reaching impact on the short-term health risks and long-term health effects of mothers and babies.At present,the relevant studies on GMD are mostly limited to the risk factors or the influence of a single disease,the association among metabolic disorders and their combined effects on pregnancy outcomes remain to be further studied.A comprehensive understanding of the prevalence of GMD among pregnant women in China and the combined effects of different types of metabolic disorders on adverse pregnancy outcomes would provide the necessary scientific basis for the in-depth research in this field,as well as the formulation of related health policies and measures,which has a high public health significance and practical application value.Objective:We aimed to describe the epidemiological characteristics of GMD and adverse pregnancy outcomes in the target cohort,to explore the association and its intensity between GMD and adverse pregnancy outcomes,and to evaluate the predictive ability of different metabolic indexes during pregnancy for adverse pregnancy outcomes.Methods:This study uses the prospective cohort study design.The maternal cohort was established from 2017 in the Maternal and Child Health Hospital of Haidian District,Beijing,by the Institute of Reproductive and Child Health,Peking University Health Science center.For pregnant women who came to the hospital for early pregnancy examination and establish pregnancy files,if they met the cohort inclusion criteria and signed the informed consent form,they would be recruited into the cohort and filled out the epidemiological questionnaire on the spot,and then they would be followed up until their delivery.Our study included pregnant women who enrolled in this cohort from October 2017 to October 2020,and already obtained pregnancy outcomes.After excluding for twins and those without GMD diagnostic basis,a total of 3265 pregnant women were included in this analysis.Epidemiological questionnaires were used to prospectively collect the information of pregnant women including general demographic characteristics,reproductive characteristics,adverse environmental exposure in early pregnancy,mood and sleep conditions,as well as their lifestyle.Subsequently,based on the routine perinatal care monitoring system,the pregnant women in the cohort were followed up to collect their weight,blood pressure,blood glucose and blood lipid levels during pregnancy,and their delivery and hospitalization records,as well as other relevant data information were regularly obtained from the hospital’s pregnancy archive electronic management system.We used the chi-square test to compare the differences in the distribution of GMD and adverse pregnancy outcomes among pregnant women in different characteristic groups.According to the incidence of each adverse pregnancy outcome,unconditional logistic regression and log-binomial regression were used to estimate the adjusted risk ratio(aRR)between GMD and the risk of different adverse pregnancy outcomes,after adjusting confounding variables such as age,occupation,education level,gravidity,parity,history of uterine surgery,as well as the history of adverse pregnancy,and we further compared the effects of simultaneous occurrence of different numbers of metabolic disorders or abnormal metabolic indexes on adverse pregnancy outcomes.We also drew the ROC curve and calculated the area under curve(AUC),sensitivity and specificity to evaluate the predictive ability of metabolic indexes on adverse pregnancy outcomes,and determined the best predictive cut-off point of each index.Results:(1)A total of 47.9%of pregnant women in this study developed GMD.Among them,the rate of overweight or obesity during pregnancy was the highest,with an incidence of 29.9%.The incidence of overweight or obesity before pregnancy was 18.3%,and the incidence of excessive weight gain during pregnancy was 14.4%.The incidence of GDM among the study subjects was 19.0%,and the incidence of GHTN and PE(including eclampsia)were 8.9%and 3.3%,respectively.In addition,a total of 11.1%of pregnant women in the cohort were diagnosed with GMS,and the incidence rates were 1.9%and 10.4%in the first trimester and the third trimester,respectively.Old age,increased gravidity or parity,low education and family income,passive smoking,low frequency of eating vegetables and fruits were all significant independent risk factors for GMD(P<0.05).(2)In this study,the incidence of premature rupture of membranes,fetal distress and postpartum hemorrhage were 25.6%,27.8%and 19.3%,respectively,which were both at a high level in China and abroad.The incidence of other major adverse pregnancy outcomes,such as preterm birth,low birth weight,small-for-gestational age,macrenia,spontaneous abortion,stillbirth and fetal malformation were 5.0%,3.7%,5.5%,5.2%,1.4%;1.2‰ and 3.2%,respectively,which were similar to the incidence reported in previous studies in China.Compared with the normal pregnancy outcome group,women with adverse pregnancy outcomes had a lower average age,lower number of gravidity or parity,and higher family income.In addition,a history of uterine surgery,a short interval from the last pregnancy,and the last pregnancy ended in miscarriage were also significant independent risk factors for adverse pregnancy outcomes(P<0.05).(3)Among pregnant women with GDM,the incidence of fetal demise was as high as 2.5%,and the occurrence risk was more than two times than that in non-GDM pregnant women(aRR=2.08,95%Cl:1.05-4.09).The incidence of fetal dysplasia and low birth weight in the GHTN group were 10.6%and 6.8%,which were about two times than in the non-GHTN group(aRR=1.85/1.92,95%CI:1.20-2.85/1.12-3.30).The incidence of fetal malformations in the GHTN group was 5.3%,after adjusting for confounding factors,the risk was approximately two times than that in the non-GHTN group(aRR=1.94,95%CI:1.06-3.53).Similar to GHTN,PE can further increase the risk of fetal dysplasia(aRR=3.40,95%CI:1.99-5.80)and low birth weight(aRR-6.85,95%CI:4.02-11.69).What’s more,the incidence of preterm birth among pregnant women with PE was as high as 19.4%in our study,which was 4.52 times than that in the non-PE group(95%CI:2.68-7.62).Among pregnant women in the gestational overweight or obese group,the incidence of macrosomia was 8.2%,and the risk was 2.04(95%CI:1.48-2.81)times than in the normal weight pregnant women.In our study,GMS,especially GMS in the third trimester,would also significantly increase the risk of macrosomia(aRR=L99,95%CI:1.31-3.01).Compared with pregnant women without metabolic disorders,the risks of low birth weight(aRR=2.02,95%CI:1.18-3.44),fetal demise(aRR=2.43,95%CI:1.06-5.56)in the group of pregnant women combined with two metabolic disorders were significantly higher.The risk of macrosomia continued rising with the increase of combined metabolic disorders number during pregnancy,and there was a significant dose-response relationship between them(P=0.001).(4)After analyzing the influence of various metabolic indexes during pregnancy on the risk of adverse pregnancy outcomes,it was found that increased diastolic and systolic blood pressure in the first and second trimesters were significantly associated with the increased risk of preterm birth and low birth weight,and increased diastolic blood pressure in the third trimester could also increase the risk of fetal dysplasia significantly.Elevated BMI before pregnancy could significantly increase the risk of macrosomia(aRR=1.11,95%CI:1.061.17),while low BMI before pregnancy was significantly associated with fetal dysplasia and fetal malformations.An increase in the average weight gain rate during pregnancy could significantly increase the risk of macrosomia(aRR=11.90,95%CI:3.17-44.63),while lower average weight gain rate during pregnancy was significantly associated with preterm birth,low birth weight and fetal dysplasia.Elevated triacylglycerol(TG)levels in the first trimester was associated with an increased risk of fetal demise(aRR=2.40,95%CI:1.35-4.29),and the increase of TG in the third trimester was significantly associated with the increased risk of preterm birth,low birth weight and fetal malformations.The decrease of fasting blood glucose in the second trimester was significantly associated with the increased risk of low birth weight and fetal dysplasia.The OGTT-1h and OGTT-2h blood glucose levels in pregnant women with fetal dysplasia were also significantly lower than those in the normal pregnancy outcome group.High fasting blood glucose in the second trimester could also increase the risk of macrosomia(aRR=1.49,95%CI:1.09-2.03).Elevated values of OGTT-1h and OGTT-2h were also significantly associated with increased risk of fetal demise.With the number of combined pregnancy metabolic index abnormalities increasing,the risk of macrosomia showed a significant upward trend(P<0.05),and the incidence of preterm birth,as well as fetal demise also increased,while the risk of other adverse pregnancy outcomes did not change significantly.(5)By drawing the ROC curves of various metabolic indexes during pregnancy and the concerned adverse pregnancy outcomes,as well as calculating the area under the curve,we found that TG in early pregnancy had certain diagnostic value for fetal demise,TG in late pregnancy was relatively good in the prediction of preterm birth and low birth weight,as well as BMI before pregnancy was relatively good in the prediction of macrosomia,with the areas under the curve were 0.633,0.643,0.666 and 0.641,respectively.Compared with single metabolic index,the combination of pre-pregnancy BMI and average weight gain rate during pregnancy had a better diagnostic value for fetal dysplasia and fetal malformation.Conclusion:(1)The incidence of GMD is quite high in China,and the risk of multiple metabolic abnormalities aggregation during pregnancy is significantly higher than that before pregnancy.(2)GMD could significantly increase the risk of a variety of adverse pregnancy outcomes,including preterm birth,macrosomia,low birth weight,fetal dysplasia,fetal malformation and fetal demise,which seriously threatens maternal and infant health.(3)Various metabolic disorders or abnormal levels of metabolic indexes have a certain combined effects on the occurrence of adverse pregnancy outcomes.Compared with the abnormality of a single metabolic index,the aggregation of multiple metabolic abnormalities during pregnancy could further increase the risk of adverse pregnancy outcomes,such as premature delivery,low birth weight,and macrosomia.(4)Some metabolic indexes have a certain predictive effect on adverse pregnancy outcomes,but the predictive value of a single metabolic index is relatively limited,and the combination of different metabolic indexes could further enhance the diagnostic value for adverse pregnancy outcomes.