| Objective:To investigate the effects of second-trimester maternal serum alfa-fetoprotein(AFP)and beta human chorionic gonadotropin(?-hCG)on other adverse pregnancy outcomes except fetal aneuploidy and neural tube defects,and their predictive value for these adverse pregnancy outcomes in different risk groups of Down's screening.Methods:The clinical data of 8 389 singleton pregnant women of appropriate age(18 years old?expected delivery age<35 years old)who underwent prenatal examination and terminated pregnancy in the First Affiliated Hospital of Soochow University from April 2015 to October 2017 were analyzed retrospectively.According to the results of Down's screening,they were divided into three groups:high risk group(21 trisomy risk?1/270 and/or 18 trisomy risk?1/350),critical risk group(1/270>21 trisomy risk?1/1000 and/or 1/350>18 trisomy risk?1/1000)and low risk group(both trisomy 21 and trisomy 18<1/1000).According to mid-trimester maternal serum AFP and ?-hCG levels,pregnant women were divided into as follows:normal level of both AFP and ?-hCG(0.4?AFP MoM?2.5 and 0.25??-hCG MoM?2.5),reduction of AFP(AFP MoM<0.4),elevation of AFP(AFP MoM>2.5),reduction of ?-hCG(?-hCG MoM<0.25)and elevation of ?-hCG(?-hCG MoM>2.5).To evaluate the relationship between different risk groups,serum marker groups and other adverse pregnancy outcomes except fetal aneuploidy and neural tube defects.The receiver working characteristic(ROC)curve was used to evaluate the value of AFP and ?-hCG in predicting adverse pregnancy outcomes in different screening risk groups,and the corresponding predictive cutoff values were obtainedResults:1.The overall incidence of adverse pregnancy outcome in the high risk group(55.2%)was significantly higher than that in the critical risk group(44.9%)and the low risk group(42.6%)(P<0.05).Compared with the low risk group,there was an increased risk of fetal malformations(excluding aneuploidy and open neural tube defects)in the critical risk group(OR=2.89,95%CI:1.15?7.62)and in the high risk group(OR=5.77,95%CI:2.14?15.55).The high risk group developed pregnancy-induced hypertension syndrome(PIH)(OR=1.98,95%CI:1.23?3.16),preterm delivery(OR=2.25,95%CI:1.53?3.31)and fetal growth restriction(FGR)(OR=2.73,95%CI:1.45?5.17).2.The levels of serum AFP and ?-hCG MoM in adverse pregnancy outcome group were significantly higher than those in non-adverse pregnancy outcome group(AFP MoM 1.09±0.40 vs.1.02±0.36,?-hCG MoM 1.29±1.24 vs.1.17±0.86)(P<0.05).3.Without considering the risk value of screening,there was no statistical difference in the risk of adverse pregnancy outcomes between the single ?-hCG reduction group and the normal group(P>0.05),except that the risk of PIH,preterm delivery,abortion,FGR,placental abruption or fetal death increased in other abnormal groups,as follows:(1)There was an increased risk of PIH(OR=1.72,95%CI:1.16?2.54),preterm delivery(OR=2.50,95%CI:1.86?3.37)and stillbirth(OR=3.93,95%CI:1.28?12.10)in the ?-hCG single elevated group.(2)The risk of PIH(OR=13.98,95%CI:3.59?54.43)and placental abruption(OR=2.74,95%CI:1.59?102.00)increased in the single AFP reduction group,and the risk of occurrence of PIH was 8.14 times higher than that in the ?-hCG single elevated group(P<0.05).(3)The risk of PIH(OR=6.38,95%CI:3.09?13.20),preterm delivery(OR=15.00,95%CI:8.60?26.15),abortion(OR=9.90,95%CI:2.30?42.53)and FGR(OR=4.53,95%CI:1.39?14.76)increased in the AFP single elevated group,and the risk of PIH and preterm delivery was 3.72 and 6.00 times higher than that in the ?-hCG single elevated group(P<0.05).(4)The risk of PIH(OR=12.24,95%CI:4.74?31.56),premature delivery(OR=9.10,95%CI:3.54?23.41),abortion(OR=58.28,95%CI:18.58?182.79),FGR(OR=7.85,95%CI:1.81?34.06),placental abruption(OR=11.47,95%CI:2.63?50.05)and stillbirth(OR=58.62,95%CI:12.42?276.76)increased in the group with both AFP and?-hCG elevated,and the risk of PIH,preterm delivery and stillbirth was 7.13,3.64 and 14.90 times higher than that in the ?-hCG single elevated group respectively(P<0.05).(5)The same adverse outcomes with increased risk,such as PIH,preterm delivery,abortion,placental abruption and stillbirth,occurred in groups with different abnormal serum indicators.There was no significant difference among the groups with single decreased and elevated AFP,and both elevated AFP and ?-hCG(P>0.05)4.The relationship between elevated serum AFP and ?-hCG and adverse pregnancy outcomes in different risk groupsBecause ?-hCG single reduction group did not increase the risk of each adverse outcome,there were 3,4 and 3 cases in the AFP single reduction group in each risk group,and 0 and 2 cases in the AFP single elevated group in the critical and high risk groups,and the number of cases was too small so that statistical analysis was not performed in these groups.(1)In the low risk group,the risk of PIH(OR=1.93,95%CI:1.01?3.71)and preterm delivery(OR=2.71,95%CI:1.64?4.47)increased in the ?-hCG single elevated group.The risk of PIH(OR=6.80,95%CI:3.28?14.12?OR=11.08,95%CI:2.22?55.24),preterm delivery(OR=14.94,95%CI:8.46?26.38?OR=14.79,95%CI:3.52?62.21)and abortion(OR=10.87,95%CI:2.51?47.09?OR=39.58,95%CI:4.70?333.68)increased in the AFP single elevated group,both AFP and ?-hCG elevated group,but there was no significant difference in the incidence of adverse outcome between the two groups(P>0.05).The incidences of PIH(17.0%vs.5.5%)and preterm delivery(37.7%vs.9.9%)in the AFP single elevated group were significantly higher than those in the ?-hCG single elevated group(P<0.05)(2)In the critical risk group,pregnant women in the group with both AFP and ?-hCG elevated had an increased risk of PIH(OR=8.89,95%CI:1.69?46.68),abortion(OR=64.22,95%CI:9.03?456.69)and FGR(OR=23.88,95%CI:4.17?136.82).The incidences of stillbirth in the ?-hCG single elevated group(1.0%)and the group with both AFP and ?-hCG elevated(12.5%)were higher than that in normal group(0%),and the incidence of stillbirth in the group with both AFP and ?-hCG elevated was significantly higher than that in the ?-hCG single elevated group(P<0.05).(3)In the high risk group,pregnant women with both AFP and ?-hCG elevated had an increased risk of PIH(OR=16.33,95%CI:2.10?126.82),preterm delivery(OR=9.60,95%CI:1.41?65.53),abortion(OR=20.00,95%CI:1.09?368.50)and placental abruption(OR=50.00,95%CI:3.71?673.31).The incidence of stillbirth(16.7%vs.0%)was also significantly higher than that in the normal group(P<0.05).There was no significant difference in the risk of adverse pregnancy outcome between the ?-hCG single elevated group and the normal serum markers group(P>0.05).5.In different risk groups,AFP,?-hCG MoM and their combined predictors were used as test variables,and each adverse pregnancy outcome was taken as state variables respectively.The ROC curve was drawn.The area under the curve(AUC)?0.70:In the low risk group,the AUC of AFP for predicting abortion was 0.70,and the predictive cutoff value was 1.07.In the critical risk group,the AUC of AFP for predicting preterm delivery was 0.75 and the predictive cutoff value was 1.12,the AUC of ?-hCG for predicting stillbirth was 0.89,the predictive cutoff value of ?-hCG was 2.88,and the AUC of AFP and combined factor(AFP MoM-?-hCG MoM×0.41)for predicting FGR was 0.70 and 0.73 respectively,and the predictive cutoff values were 1.06 and 0.45 respectively.In the high risk group,the AUC of AFP for predicting preterm delivery was 0.72,and the predictive cutoff value was 1.22.When greater than these predicted thresholds,the risk of the corresponding adverse outcome increased(P<0.05).Conclusion:1.In addition to fetal aneuploidy and open neural tube defects,the incidence of overall adverse pregnancy outcome in high risk pregnant women increases.The risk of other malformations increases in both the critical risk and the high risk group,and so does the risk of PIH,preterm delivery and FGR in the high risk group.2.In the second trimester,the abnormal maternal serum AFP MoM value and the increase of ?-hCG MoM value indicate the increased risk of adverse pregnancy outcome(mainly PIH,preterm delivery,abortion,FGR,placental abruption or stillbirth),especially when the two serum makers both increase.In terms of increasing the risk of PIH and preterm delivery,the influence of single abnormal AFP is greater than single elevated?-hCG.Single ?-hCG reduction is not associated with adverse pregnancy outcomes3.In different risk groups,the risk of PIH,abortion and/or preterm delivery increases in patients with combined elevation of AFP and ?-hCG,and FGR,stillbirth or placental abruption should be vigilant in critical risk and high risk group.Those with non-high risk but with elevated serum levels of single AFP or ?-hCG will increase risk of PIH,preterm delivery,abortion or stillbirth,and monitoring and follow-up should also be strengthened4.In different risk groups,the value of AFP and ?-hCG in predicting adverse pregnancy outcomes is different.In the low risk group,AFP MoM>1.07 increases the risk of abortion.In the critical risk group,AFP MoM>1.12 increases the risk of premature birth.AFP MoM>1.06 and the combined factor>0.45 increase the risk of FGR,and the value of combined factor in predicting FGR is better than that of single marker.When?-hCG MoM is greater than 2.88,the risk of stillbirth increases.In the high risk group,AFP MoM>1.22 increases the risk of preterm birth. |
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