Study On The Correlation Between Serum Levels Of C-Reactive Protein,C3,C4,Ferritin And Preterm Birth In Pregnant Women

BackgroundPreterm birth is the most common cause of death in infants worldwide.About 15 million babies were born prematurely each year,and the incidence rate of all births is 5%-18%.At present,4 million newborn infants still die every year in the world.In addition,preterm birth seriously affects the long-term quality of life of premature infants.The occurrence of prematurity may be affected by maternal factors,factors during pregnancy,infection and heredity.Although the reason is unknown,yet most research evidence indicates that the most common and important factors for preterm birth are infection and inflammation.C-reactive protein（CRP）,complement C3,C4 and ferritin are related indicators of inflammatory response.ObjectiveFor the first time in this study,serum levels of CRP,C3,C4 and ferritin in pregnant women with live births in Guangxi were examined,and their relationship with preterm birth was discussed.MethodsA NCC study was conducted by the Guangxi Birth Cohort Study which enrolled a total of 6,203 pregnant women between 5^0/7 and 34^6/7 weeks of gestational age（wGA）from six cities in China between July and September in2015.All participants were followed until the end of pregnancy.As a result,5541 participants had pregnancy outcomes and 662 participants lost their follow-up.Subjects were selected from those who had pregnancy outcomes for the NCC study on the basis of the cohort study.206 women who delivered preterm(<37^0/7 wGA)and 412 term deliveries matched on maternal age,birth place,gender of infants,and wGA at blood collection.All samples were sent to the laboratory of the First Affiliated Hospital of Guangxi Medical University for testing to ensure the quality of the test results.Serum CRP,C3 and C4 levels were measured by immunoturbidimetric assay,and ferritin levels were quantified by automated electrochemiluminescence immunoassay.Data were analyzed using IBM SPSS Statistics software（version 19.0,SPSS,Inc.,Chicago,IL）and summarized using descriptive statistics.Student’s test for continuous variables and chi-square statistics for categorical variables was used to investigate the differences between cases and controls.Effect estimates are presented as odds ratios（ORs）with 95%confidence intervals（C.I.）by using conditional logistic regression analysis.The statistical significance level was set at 5%and all P values were two-tailed.Results1.There were 618 pregnant women included in this nested case-control study.the average age of pregnant women was 28.29±4.91 years old,the youngest was 18 years old,and the oldest was 45 years old.The average gestational age was 17.97±6.68 weeks,the largest gestational age was 32 weeks and the minimum was 6 weeks.Among the subjects,there were 365 pregnant women who were in the first pregnancy,which account for 59.06%.345 cases of preterm birth were recruited in the study,the incidence of preterm birth was6.23%.2.After standardization of national preterm birth rate,the standardized incidence ratio of preterm birth in our study was 0.86.3.The level of serum CRP in the preterm group was significantly higher than control group（P<0.05）.4.In the stratified analysis of pregnancy weeks,we found that the serum levels of CRP,C3 and ferritin in pregnant women in the control group had statistically significant differences between the three trimesters（P<0.01）.The levels of CRP and C3 were higher than those of the control group（P<0.05）.Highest quartile concentrations of all inflammatory indicators were determined versus median.After adjusting for maternal age,CRP levels are closely related to the rise risk of PTB（OR=2.16,95%CI:1.02-4.56 for CRP>16.60 mg/L,P=0.044）in the first trimester.The association of C3 was extremely related to those who experienced PTB（OR=2.53,95%CI:1.14-5.64,P=0.023）versus term birth.Moreover,no significant association was found in C4（P=0.079）and ferritin（P=0.067）between PTB.High concentrations of C4 and ferritin levels were not significantly associated with the risk of preterm birth（OR=1.89,95%CI:0.93,3.85,P=0.079;OR=2.03,95%CI:0.95,4.34,P=0.067,respectively）.In the second and third trimesters,serum CRP,C3,C4,and ferritin levels were not associated with preterm birth（P<0.05）.5.In the stratification of pregnant outcomes,after adjusting for maternal age,high-level C3 was significantly associated with the risk of spontaneous preterm birth（OR=2.26,95%CI=1.18,4.33）,while other indicators no association was found with the risk of spontaneous preterm birth（CRP:OR=1.39,95%CI=0.75,2.57;C4:OR=1.59,95%CI=0.88,2.84;Ferritin:OR=1.52,95%CI=0.84,2.76,respectively）.In the analysis of premature rupture of membranes,serum CRP,C3,C4 and ferritin were not significantly associated with the risk of premature rupture of membranes（all measures P>0.05）.ConclusionsElevated concentrations of CRP and C3 in the first trimester were associated with increased risk of PTB.In addition,high levels of C3 were associated with the risk of spontaneous preterm birth.Inflammatory indicators may act a pivotal part in early diagnosis and prognosis of PTB.