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Background. The relationship among elevated serum β-human chorionic gonadotropin (β-hCG), the incidence of pregnancy complications, and adverse pregnancy outcomes has been controversial. Differences in study design, subject bias due to demographic characteristics, and differences in local medical levels could contribute to inconsistent results. Methods. Literature searches were performed in PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science Digital Library (CSDL) databases. Inclusion criteria were as follows: (1) research subjects were singleton pregnant women; (2) the study is identified as cohort study; (3) the subjects were assigned to the high β-hCG group and control group according to whether the exposure factors increased β-hCG in the second trimester; (4) the observed outcomes include at least pregnancy-induced hypertension (PIH), diabetes (gestational diabetes mellitus, GMD), preterm delivery (PD), and intrauterine growth restriction (IUGR); and (5) the odds ratio (OR) and 95% confidence interval (CI) of exposure factors are calculated based on literature dataset. To determine the risk bias of selected literatures, Newcastle-Ottawa scale was applied. The chi-square test was further used for heterogeneity analysis. If heterogeneity was identified, subgroup analyses were then performed for source investigation. Results. A total of 13 literatures were included and analyzed, including 67,355 pregnant women and 5980 pregnant women assigned to the high β-HCG group and 61,375 pregnant women to the control group. The incidence of PIH in the high β-HCG group was higher than that in the control group ( OR = 2.11 , 95% CI [1.90, 2.35], Z = 13.85 , P < 0.00001 ). There was no heterogeneity among literatures ( χ 2 = 8.53 , P = 0.38 , I 2 = 6 % ), and thus there is no identified publication bias ( P > 0.05 ). The incidence of preterm birth in the high β-HCG group was higher than that in the control group ( OR = 2.11 , 95% CI [1.90, 2.35], Z = 13.85 , P < 0.00001 ). The analysis suggested no heterogeneity among included literatures ( χ 2 = 11.78 , P = 0.11 , I 2 = 41 % ) and no publication bias ( P > 0.05 ). Higher incidence of abortion was observed in the high β-HCG group compared with the control group ( OR = 2.80 , 95% CI [1.92, 4.09], Z = 5.32 , P < 0.00001 ). There was no heterogeneity among literatures ( χ 2 = 3.43 , P = 0.33 , I 2 = 13 % ) and no publication bias ( P > 0.05 ). The incidence of gestational diabetes was higher in the high β-HCG group than in the control group ( OR = 2.15 , 95% CI [1.05, 4.40], Z = 2.09 , P = 0.04 ). Heterogeneity was identified among literatures ( χ 2 = 47.01 , P < 0.00001 , I 2 = 87 % ). Sensitivity analysis showed that the results were not robust, and there was no publication bias ( P > 0.05 ). Compared with control, the incidence of IGUR was higher in the high β-HCG group ( OR = 2.70 , 95% CI [1.75, 4.19], Z = 4.45 , P < 0.0001 ) with no heterogeneity among literatures ( χ 2 = 3.92 , P = 0.14 , I 2 = 49 % ) and no publication bias ( P > 0.05 ). Conclusion. High levels of β-hCG during pregnancy in singleton women are associated with a high incidence of pregnancy complications and adverse pregnancy outcomes. Pregnant women with high levels of β-hCG should be monitored more closely, followed up, and given timely medical interventions to reduce the incidence of pregnancy complications and adverse outcomes.
Background. The relationship among elevated serum β-human chorionic gonadotropin (β-hCG), the incidence of pregnancy complications, and adverse pregnancy outcomes has been controversial. Differences in study design, subject bias due to demographic characteristics, and differences in local medical levels could contribute to inconsistent results. Methods. Literature searches were performed in PubMed, EMBASE, Medline, Central, China National Knowledge Infrastructure (CNKI), Wanfang, and China Science Digital Library (CSDL) databases. Inclusion criteria were as follows: (1) research subjects were singleton pregnant women; (2) the study is identified as cohort study; (3) the subjects were assigned to the high β-hCG group and control group according to whether the exposure factors increased β-hCG in the second trimester; (4) the observed outcomes include at least pregnancy-induced hypertension (PIH), diabetes (gestational diabetes mellitus, GMD), preterm delivery (PD), and intrauterine growth restriction (IUGR); and (5) the odds ratio (OR) and 95% confidence interval (CI) of exposure factors are calculated based on literature dataset. To determine the risk bias of selected literatures, Newcastle-Ottawa scale was applied. The chi-square test was further used for heterogeneity analysis. If heterogeneity was identified, subgroup analyses were then performed for source investigation. Results. A total of 13 literatures were included and analyzed, including 67,355 pregnant women and 5980 pregnant women assigned to the high β-HCG group and 61,375 pregnant women to the control group. The incidence of PIH in the high β-HCG group was higher than that in the control group ( OR = 2.11 , 95% CI [1.90, 2.35], Z = 13.85 , P < 0.00001 ). There was no heterogeneity among literatures ( χ 2 = 8.53 , P = 0.38 , I 2 = 6 % ), and thus there is no identified publication bias ( P > 0.05 ). The incidence of preterm birth in the high β-HCG group was higher than that in the control group ( OR = 2.11 , 95% CI [1.90, 2.35], Z = 13.85 , P < 0.00001 ). The analysis suggested no heterogeneity among included literatures ( χ 2 = 11.78 , P = 0.11 , I 2 = 41 % ) and no publication bias ( P > 0.05 ). Higher incidence of abortion was observed in the high β-HCG group compared with the control group ( OR = 2.80 , 95% CI [1.92, 4.09], Z = 5.32 , P < 0.00001 ). There was no heterogeneity among literatures ( χ 2 = 3.43 , P = 0.33 , I 2 = 13 % ) and no publication bias ( P > 0.05 ). The incidence of gestational diabetes was higher in the high β-HCG group than in the control group ( OR = 2.15 , 95% CI [1.05, 4.40], Z = 2.09 , P = 0.04 ). Heterogeneity was identified among literatures ( χ 2 = 47.01 , P < 0.00001 , I 2 = 87 % ). Sensitivity analysis showed that the results were not robust, and there was no publication bias ( P > 0.05 ). Compared with control, the incidence of IGUR was higher in the high β-HCG group ( OR = 2.70 , 95% CI [1.75, 4.19], Z = 4.45 , P < 0.0001 ) with no heterogeneity among literatures ( χ 2 = 3.92 , P = 0.14 , I 2 = 49 % ) and no publication bias ( P > 0.05 ). Conclusion. High levels of β-hCG during pregnancy in singleton women are associated with a high incidence of pregnancy complications and adverse pregnancy outcomes. Pregnant women with high levels of β-hCG should be monitored more closely, followed up, and given timely medical interventions to reduce the incidence of pregnancy complications and adverse outcomes.
This study assessed the correlation between the magnitude of the elevation in maternal serum human chorionic gonadotropin (MShCG) levels and pregnancy complications. Among 80,716 screened pregnancies, 120 with moderately elevated MShCG (3.00-5.99 MoM) were compared to 84 with extremely elevated MShCG >6.00 MoM. A control series of 120 women with normal MShCG (<3.00 MoM) were matched. Rates of intrauterine growth restriction, preterm labour, antepartum foetal death (APFD), pre-eclampsia, and placental abruption were analysed. We found that the study group had more adverse outcomes than the control group (73/204 [36%] vs. 18/120 [15%]; p < .0001). The rate was higher in the extremely elevated group than in the moderately elevated group (43/84 [51%] vs. 30/120 [25%]; p < .0001). All 12 cases of APFD (14%) occurred among the extremely elevated series. In conclusion, adverse pregnancy outcomes are more common in women with extremely elevated MShCG. The patients should receive counselling regarding this trend and undergo close pregnancy monitoring. Impact statement • What is already known on this subject?In addition to its contribution to Down syndrome (DS) screening, maternal serum human chorionic gonadotropin (MShCG) levels are a marker for pregnancy complications such as intrauterine growth restriction (IUGR), preterm labour (PTL), antepartum fatal death (APFD), pre-eclampsia (PE), placental abruption (PA) and fetal malformations with or without chromosomal aberrations. • What the results of this study add? We found that in the presence of elevated MShCG levels, the incidence of IUGR and PTL increased. PE increased clinically, but statistical significance was seen only when MShCG was extremely elevated (≥ 6.00 MoM). APFD and PA were associated with very high MShCG levels only. • What the implications are of these findings for clinical practice and/or further research? Women with high MShCG levels should be counselled. In case of very high levels (≥ 6.00 MoM), the risk of APFD and PA should be discussed. The pregnancy should be monitored for IUGR, PTL and PE. In view of the limited number of enrolled patients with very high levels of MShCG, the experience of other institutions is needed to corroborate these findings.
Background Bioactive proteins, such as cytokines and chemokines, have not been systematically evaluated in healthy and preeclamptic pregnancies. We aimed to investigate the difference of these proteins between healthy and preeclamptic pregnancies in order to help clarify their potential roles in the pathogenesis of hypertension and proteinuria in preeclampsia. Methods Samples of amniotic fluid and maternal/umbilical cord blood were collected from normal pregnancies and women with preeclampsia for examination of bioactive proteins. Fifty-three pregnant women were enrolled in this study. Of them, 30 pregnant women were recruited as healthy controls, and 23 pregnant women were diagnosed with preeclampsia. An antibody array was used to screen for higher levels of cytokines and related proteins in amniotic fluid than in the blood samples, and these proteins were then selected for quantification by immunoassay. Results Interleukin-1 receptor 4, hepatocyte growth factor, and urokinase plasminogen activator receptor were significantly elevated in the blood of preeclampsia patients. In particular, interleukin-1 receptor 4 was 8-fold higher in preeclampsia patients than in the healthy pregnancies. Moreover, in cord blood samples hepatocyte growth factor and interleukin-8 were significantly higher in preeclampsia patients. Conclusions Because of the biologic activities, Interleukin-1 receptor 4, hepatocyte growth factor, urokinase plasminogen activator receptor and interleukin-8 in maternal and/or cord blood could play a role in the pathogenesis of hypertension and proteinuria in preeclampsia.
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