Maternal Plasma and Amniotic Fluid LBP, Pentraxin 3, Resistin, and IGFBP-3:Biomarkers of Microbial Invasion of Amniotic Cavity and/or Intra-amniotic Inflammation in Women with Preterm Premature Rupture of Membranes

Background@#We sought to determine whether lipopolysaccharide binding protein (LBP), pentraxin 3, resistin, and insulin-like growth factor binding protein (IGFBP)-3 in plasma and amniotic fluid (AF) can predict microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI), and microbial-associated IAI in women with preterm premature rupture of membranes (PPROM). @*Methods@#This was a retrospective cohort study involving 168 singleton pregnant women with PPROM. AF obtained via amniocentesis was cultured and assayed for interleukin (IL)-6 to define IAI and for IL-8 to compare with AF biomarkers. Plasma samples were collected at the time of amniocentesis, and C-reactive protein (CRP) levels in serum were compared with plasma biomarkers. The stored plasma and AF samples were assayed for LBP, pentraxin 3 (PTX3), resistin, and IGFBP-3 by ELISA. @*Results@#Multivariate logistic regression analysis revealed that: 1) elevated plasma and AF levels of LBP were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 2) elevated AF, but not plasma, PTX3, and resistin levels were independently associated with increased risks of MIAC, IAI, and microbial-associated IAI; 3) decreased IGFBP-3 levels in the plasma were independently associated with only IAI, whereas those in the AF were associated with only microbial-associated IAI. Among the tested biomarkers, AF PTX3 and resistin had the highest predictive performance for MIAC, IAI, and microbial-associated IAI (area under the curves [AUC] = 0.85–0.95), which is similar to the performance of AF IL-8. The AUCs of the plasma LBP and IGFBP-3 were similar to that of serum CRP with respect to IAI. @*Conclusion@#Maternal plasma LBP and IGFBP-3 are potential biomarkers for the non-invasive identification of IAI in women with PPROM, with a similar accuracy to the serum CRP level.AF LBP, PTX3, resistin, and IGFBP-3 may be involved in the intra-amniotic inflammatory responses in PPROM complicated by MIAC.

Funisitis as a Risk Factor for Adverse Neonatal Outcomes in Twin Neonates with Spontaneous Preterm Birth: A Retrospective Cohort Study

Purpose@#Funisitis, inflammation of the umbilical cord, is considered a strong risk factor for adverse neonatal outcomes; however, a clinical definition of funisitis has not been established. In this study, we aimed to determine the clinical significance of funisitis in twin neonates with spontaneous preterm birth. @*Materials and Methods@#The study included preterm twin neonates (<35 weeks) delivered after spontaneous preterm labor and/ or preterm premature rupture of amniotic membranes. The presence of funisitis was examined in the umbilical cord of each twin.We analyzed the risk of adverse neonatal outcomes according to the presence and absence of funisitis. Adverse neonatal outcomes were defined as the occurrence of neonatal mortality, significant morbidity, or both. @*Results@#Among 474 preterm neonates (237 twin pairs) included in this study, the frequency of funisitis was 6.5% (31 cases). Funisitis was significantly associated with neonatal mortality and adverse neonatal outcomes after adjustment for confounding variables [neonatal mortality, odds ratio (OR) 9.043, 95% confidence interval (CI) 2.620–31.204; adverse neonatal outcome, OR 2.445, 95% CI 1.017–5.875]. The concordance rate of funisitis between the twins was 10.7%, and in the absence of funisitis in one twin, the risk of neonatal mortality or adverse neonatal outcome was not influenced by the presence of funisitis in the other twin. @*Conclusion@#The presence of funisitis appears to be associated with an increased risk for adverse neonatal outcomes in twin neonates with spontaneous preterm birth.

Funisitis as a Risk Factor for Adverse Neonatal Outcomes in Twin Neonates with Spontaneous Preterm Birth: A Retrospective Cohort Study

Purpose@#Funisitis, inflammation of the umbilical cord, is considered a strong risk factor for adverse neonatal outcomes; however, a clinical definition of funisitis has not been established. In this study, we aimed to determine the clinical significance of funisitis in twin neonates with spontaneous preterm birth. @*Materials and Methods@#The study included preterm twin neonates (<35 weeks) delivered after spontaneous preterm labor and/ or preterm premature rupture of amniotic membranes. The presence of funisitis was examined in the umbilical cord of each twin.We analyzed the risk of adverse neonatal outcomes according to the presence and absence of funisitis. Adverse neonatal outcomes were defined as the occurrence of neonatal mortality, significant morbidity, or both. @*Results@#Among 474 preterm neonates (237 twin pairs) included in this study, the frequency of funisitis was 6.5% (31 cases). Funisitis was significantly associated with neonatal mortality and adverse neonatal outcomes after adjustment for confounding variables [neonatal mortality, odds ratio (OR) 9.043, 95% confidence interval (CI) 2.620–31.204; adverse neonatal outcome, OR 2.445, 95% CI 1.017–5.875]. The concordance rate of funisitis between the twins was 10.7%, and in the absence of funisitis in one twin, the risk of neonatal mortality or adverse neonatal outcome was not influenced by the presence of funisitis in the other twin. @*Conclusion@#The presence of funisitis appears to be associated with an increased risk for adverse neonatal outcomes in twin neonates with spontaneous preterm birth.

A Comparison of Predictive Performances between Old versus New Criteria in a Risk-Based Screening Strategy for Gestational Diabetes Mellitus

Background@#The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria. @*Methods@#This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach. @*Results@#Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P<0.001). @*Conclusion@#Compared with the old criteria, use of the new criteria would have decreased the number of patients identified as high risk and thus requiring early GDM screening by half (from 244 [29.8%] to 131 [16.0%]).

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery

OBJECTIVE: To compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD).METHODS: Among 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies.RESULTS: The median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9–35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7–38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7–39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64–3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44–3.36 kg) in the non-HCA group; P>0.1 for all.CONCLUSION: The presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix

BACKGROUND: We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).METHODS: This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.RESULTS: The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.CONCLUSION: In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

Gestational weight gain in twin pregnancies in Korea: application of the 2009 Institute of Medicine recommendations

Objective@#To investigate the effect of gestational weight gain (GWG) on maternal and neonatal outcomes based on the Institute of Medicine (IOM) guidelines for twin pregnancies. @*Methods@#This study included women with twin pregnancies who delivered at Seoul National University Bundang Hospital. Based on the weight gain per gestational week according to the 2009 IOM guidelines, the subjects were divided into the following 3 groups: inadequate, adequate, and excessive GWG. We compared the maternal and neonatal outcomes of each group. @*Results@#A total of 1,738 twin pregnancies were included in our study. Of these cases, 881, 694, and 163 (50.7%, 39.9%, and 9.4%, respectively) twin pregnancies were categorized into the inadequate, adequate, and excessive GWG groups, respectively. In the inadequate GWG group, the risks of preterm birth <34 weeks (aOR, 2.33, 95% confidence interval [CI], 1.63–3.34) and delivering neonates who were small for gestational age (aOR, 1.92, 95% CI, 1.42–2.60) were increased, and the risk of preeclampsia (aOR, 0.49, 95% CI, 0.32–0.76) was decreased. The excessive GWG group had an increased risk of the neonates being large for gestational age (aOR, 1.79, 95% CI, 1.15–2.81). @*Conclusion@#The 2009 IOM recommendations for GWG can be applied to Korean women with twin pregnancies to help achieve optimal maternal and neonatal outcomes. However, more than half of the women were categorized as having inadequate weight gain according to the guidelines. Further studies should be performed to obtain Korean national references for GWG in twin pregnancies.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix

BACKGROUND@#We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).@*METHODS@#This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.@*RESULTS@#The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.@*CONCLUSION@#In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

The Identification of Immune-Related Plasma Proteins Associated with Spontaneous Preterm Delivery and Intra-Amniotic Infection in Women with Premature Cervical Dilation or an Asymptomatic Short Cervix

BACKGROUND@#We aimed to investigate whether various immune-related plasma proteins, alone or in combination with conventional clinical risk factors, can predict spontaneous preterm delivery (SPTD) and intra-amniotic infection in women with premature cervical dilation or a short cervix (≤ 25 mm).@*METHODS@#This retrospective study included 80 asymptomatic women with premature cervical dilation (n = 50) or a short cervix (n = 30), who underwent amniocentesis at 17–29 weeks. Amniotic fluid (AF) was cultured, and maternal plasma was assayed for interleukin (IL)-6, matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and complements C3a and C5a, using enzyme-linked immunosorbent assay (ELISA) kits. The primary outcome measures were SPTD at < 32 weeks and positive AF cultures.@*RESULTS@#The plasma levels of IL-6, C3a, and C5a, but not of MMP-9 and TIMP-1, were significantly higher in women with SPTD at < 32 weeks than in those who delivered at ≥ 32 weeks. The women who delivered at < 32 weeks had more advanced cervical dilatation, and higher rates of antibiotic and tocolytic administration and were less likely to be given vaginal progesterone than those who delivered at ≥ 32 weeks. Using a stepwise regression analysis, a combined prediction model was developed, which included the plasma IL-6 and C3a levels, and cervical dilatation (area under the curve [AUC], 0.901). The AUC for this model was significantly greater than that for any single variable included in the predictive model. In the univariate analysis, plasma IL-6 level was the only significant predictor of intra-amniotic infection.@*CONCLUSION@#In women with premature cervical dilation or a short cervix, maternal plasma IL-6, C3a, and C5a levels could be useful non-invasive predictors of SPTD at < 32 weeks. A combination of these biomarkers and conventional clinical factors may clearly improve the predictability for SPTD, as compared with the biomarkers alone. An increased plasma level of IL-6 predicted intra-amniotic infection.

Gestational weight gain in twin pregnancies in Korea: application of the 2009 Institute of Medicine recommendations

Objective@#To investigate the effect of gestational weight gain (GWG) on maternal and neonatal outcomes based on the Institute of Medicine (IOM) guidelines for twin pregnancies. @*Methods@#This study included women with twin pregnancies who delivered at Seoul National University Bundang Hospital. Based on the weight gain per gestational week according to the 2009 IOM guidelines, the subjects were divided into the following 3 groups: inadequate, adequate, and excessive GWG. We compared the maternal and neonatal outcomes of each group. @*Results@#A total of 1,738 twin pregnancies were included in our study. Of these cases, 881, 694, and 163 (50.7%, 39.9%, and 9.4%, respectively) twin pregnancies were categorized into the inadequate, adequate, and excessive GWG groups, respectively. In the inadequate GWG group, the risks of preterm birth <34 weeks (aOR, 2.33, 95% confidence interval [CI], 1.63–3.34) and delivering neonates who were small for gestational age (aOR, 1.92, 95% CI, 1.42–2.60) were increased, and the risk of preeclampsia (aOR, 0.49, 95% CI, 0.32–0.76) was decreased. The excessive GWG group had an increased risk of the neonates being large for gestational age (aOR, 1.79, 95% CI, 1.15–2.81). @*Conclusion@#The 2009 IOM recommendations for GWG can be applied to Korean women with twin pregnancies to help achieve optimal maternal and neonatal outcomes. However, more than half of the women were categorized as having inadequate weight gain according to the guidelines. Further studies should be performed to obtain Korean national references for GWG in twin pregnancies.