Maternal serum advanced glycation end products level as an early marker for predicting preterm labor/PPROM: a prospective preliminary study

Objective: To evaluate the value of maternal serum advanced glycation end products (AGEs) level at 11–13 weeks’ gestation for the prediction of preterm labor and or preterm premature rupture of membranes (PPROM).

Materials and methods: This prospective cross-sectional study is performed in a university-affiliated hospital between February and April 2016. The participants of this study are low-risk pregnant women. Blood samples for maternal AGEs level were collected in the first trimester of pregnancy and all women completed their antenatal follow-up and delivered in our center. During the follow-up 21 women developed preterm labor/PPROM. The first trimester maternal AGEs levels of preterm labor/PPROM cases were compared with uncomplicated cases (n?=?25) matched for age-parity and BMI. The predictive value of AGEs levels for preterm labor/PPROM was also assessed.

Results: First-trimester AGEs levels were significantly higher in cases complicated with preterm labor/PPROM (1832 (415–6682) versus 1276 (466–6445) ng/L, p?=?.001 and 1722 (804–6682) versus 1343 (466–6445) ng/L, p?=?.025). According to receiver-operating characteristic curve analysis, the calculated cut off value of AGEs was 1538?ng/L with the sensitivity 91.7%, specificity 73.8%; and the negative and positive predictive values were 91.6% and 29.5%, respectively.

Conclusions: For the prediction of preterm labor/PPROM, the relatively high AGEs levels in the first trimester might be a useful marker.     

Amniotic fluid heat shock protein 70 concentration in histologic chorioamnionitis,term and preterm parturition

Objective. Heat shock protein (HSP) 70, a conserved member of the stress protein family, is produced in almost all cell types in response to a wide range of stressful stimuli, and its production has a survival value. Evidence suggests that extracellular HSP70 is involved in the activation of the innate and adaptive immune response. Furthermore, increased mRNA expression of HSP70 has been observed in human fetal membranes following endotoxin stimulation. This study was conducted to determine the changes in amniotic fluid HSP70 concentrations during pregnancy, term and preterm parturition, intra-amniotic infection (IAI), and histologic chorioamnionitis.

Study design. A cross-sectional study was conducted in 376 pregnant women in the following groups: (1) women with a normal pregnancy who were classified into the following categories: (a) women in the mid-trimester (14–18 weeks) who underwent amniocentesis for genetic indications and delivered normal infants at term (n=72); (b) women at term not in labor (n = 23); and (c) those at term in labor (n = 48). (2) Women with spontaneous preterm labor and intact membranes who were subdivided into the following categories: (a) preterm labor who delivered at term without IAI (n = 42); (b) preterm labor who delivered preterm without IAI (n = 57); and (c) preterm labor and delivery with IAI (n = 30). (3) Women with preterm prelabor rupture of membranes (PROM) with (n = 50) and without (n = 54) IAI. Among patients with preterm labor with intact membranes and preterm PROM who delivered within 72 hours of amniocentesis, placenta, umbilical cord, and chorioamniotic membranes were collected and assessed for the presence or absence of acute inflammatory lesions in the extraplacental membranes (histologic chorioamnionitis) and/or umbilical cords (funisitis). HSP70 concentrations in amniotic fluid were determined using a sensitive and specific immunoassay. Non-parametric statistics were used for analysis. A p value of <0.05 was considered statistically significant.

Results. Immunoreactive HSP70 was detected in 88% (332/376) of amniotic fluid samples. The median amniotic fluid HSP70 concentration was significantly higher in women at term without labor than in those in the mid-trimester (term no labor: median 34.9 ng/mL, range 0–78.1 ng/mL vs. mid-trimester; median 6.6 ng/mL, range 0–20.8 ng/mL; p<0.001). Among patients with spontaneous preterm labor and preterm PROM, those with IAI had a significantly higher median amniotic fluid HSP70 concentration than those without IAI (preterm labor with IAI: median 82.9 ng/mL, range 0–500 ng/mL vs. preterm labor without IAI: median 41.7 ng/mL, range 0–244 ng/mL; p = 0.001; preterm PROM with IAI: median 86.5 ng/mL, range 0–428 ng/mL vs. preterm PROM without IAI: median 55.9 ng/mL, range 14.9–299.9 ng/mL; p = 0.007). There was no significant difference in the median amniotic fluid HSP70 concentration between patients with preterm labor who delivered preterm without IAI and those who delivered at term (p = 0.6). However, among patients with preterm labor without IAI, there was an inverse relationship between amniotic fluid concentration of HSP70 and the amniocentesis-to-spontaneous delivery interval (Spearman's Rho = ?0.26; p = 0.02). Patients with histologic chorioamnionitis/funisitis had a significantly higher median amniotic fluid HSP70 concentration than those without inflammation (inflammation: median 108.7 ng/mL, range 0–500 ng/mL vs. without inflammation: median 67.9 ng/mL, range 7.1–299.9 ng/mL; p = 0.02). Women at term in labor had a median amniotic fluid concentration of HSP70 significantly higher than those not in labor (term in labor: median 60.7 ng/mL, range 0–359.9 ng/mL vs. term not in labor: median 34.9 ng/mL, range 0–78.1 ng/mL; p = 0.02).

Conclusions. Intra-amniotic infection, histologic chorioamnionitis, and term parturition are associated with elevated amniotic fluid HSP70 concentrations. HSP70 plays a role in the host defense mechanism by activating the innate arm of the immune response in women with intrauterine infection. The mechanisms of preterm and term parturition in humans may involve extracellular HSP70.     

Amniotic fluid CD200 levels in pregnancies complicated by preterm prelabor rupture of the membranes

Abstract

Objective: To determine the amniotic fluid CD200 levels in uncomplicated pregnancies and in preterm prelabor rupture of the membranes (PPROM) according to microbial invasion of the amniotic cavity and histological chorioamnionitis and its association with neonatal outcomes.

Methods: One hundred and fifty-nine women with singleton pregnancies were included in this study. Amniotic fluid was collected, and CD200 levels were determined using ELISA.

Results: No difference was found in CD200 levels between women in the second trimester and women at term without labor. Women at term with labor had higher CD200 levels than women in the second trimester and women at term without labor. The presence of funisitis in PPROM pregnancies was associated with higher CD200 levels independent of gestational age (with funisitis: median 197.5?pg/mL versus without funisitis: median 61.0?pg/mL; p?=?0.003). The need for tracheal intubation and the development of bronchopulmonary dysplasia were associated with higher CD200 levels.

Conclusions: Amniotic fluid CD200 levels remained stable in advanced pregnancy and they were increased during parturition. Elevated CD200 levels in the presence of funisitis suggest the involvement of negative regulatory mechanisms of innate immunity. CD200 may play a role in the development of pulmonary aspects of neonatal morbidity.     

A link between a hemostatic disorder and preterm PROM: a role for tissue factor and tissue factor pathway inhibitor

Objective.?Vaginal bleeding is a risk factor for preterm PROM (PPROM). A disorder of decidual hemostasis has been implicated in the genesis of PROM. Indeed, excessive thrombin generation has been demonstrated in PPROM both before and at the time of diagnosis. Decidua is a potent source of tissue factor (TF), the most powerful natural pro-coagulant. A decidual hemostatic disorder may link vaginal bleeding, PPROM and placental abruption. This study was conducted to determine the behaviour of maternal TF and its natural inhibitor, the tissue factor pathway inhibitor (TFPI) in PPROM.

Methods.?This cross-sectional study included women with PPROM (n = 123) and women with normal pregnancies (n = 86). Plasma concentrations of TF and TFPI were measured by a sensitive immunoassay. Non-parametric statistics were used for analysis.

Results.?(1) The median maternal plasma TF concentration was significantly higher in patients with PPROM than in women with normal pregnancies (median: 369.5 pg/mL; range: 3.27–2551 pg/mL vs. median: 291.5 pg/mL; range: 6.3–2662.2 pg/mL respectively, p = 0.001); (2) the median maternal TFPI plasma concentration was significantly lower in patients with PPROM than in women with normal pregnancies (median: 58.7 ng/mL; range: 26.3–116 ng/mL vs. median: 66.1 ng/mL; range: 14.3–86.5 ng/mL respectively, p = 0.019); (3) there was no correlation between the plasma concentration of TF and TFPI and the gestational age at sample collection; and (4) among patients with PPROM there was no association between the presence of intra-amniotic infection or inflammation and median plasma concentrations of TF and TFPI.

Conclusions.?(1) Patients with PPROM have a higher median plasma concentration of TF and a lower median plasma concentration of TFPI than women with normal pregnancies. (2) These findings suggest that PPROM is associated with specific changes in the hemostatic/coagulation system.     

Irisin as an early marker for predicting gestational diabetes mellitus: a prospective study

Objective: The objective of this study is to evaluate maternal serum irisin levels in the first and second trimesters of pregnancy in women diagnosed with and without gestational diabetes mellitus (GDM).

Methods: We performed a prospective, nested case–control study in 258 pregnant women who were enrolled at the time of the first prenatal visit (6–11th weeks of gestation) and followed until delivery. Among the entire population, we selected 20 women who subsequently developed GDM and 30 women with uneventful pregnancies. Blood samples were collected once from each participant at 6–11th weeks of gestation during the fetal viability scan and at 24–28th weeks of gestation during screening for GDM.

Results: In the first trimester, irisin levels were significantly lower in women who later developed GDM (median?=?453?ng/mL, range: 257–811?ng/mL) than in controls (median?=?721?ng/mL, range: 700–786?ng/mL). In the second trimester, the difference in irisin levels between the GDM group (median?=?749?ng/mL; range: 456–910?ng/mL) and controls (median?=?757?ng/mL; range: 703–898?ng/mL) was not statistically significant.

Conclusions: Irisin may be a useful biomarker in early pregnancy to predict the development of GDM.     

Maternal serum calponin 1 level as a biomarker for the short-term prediction of preterm birth in women with threatened preterm labor

Purpose: To assess the utility of maternal serum calponin 1 level in the prediction of delivery within 7 days among pregnancies complicated with threatened preterm labor.

Materials and methods: Eligible women who presented at 24–34 weeks of gestation with threatened preterm labor underwent sampling for serum calponin 1 level and cervical length measurement. They were followed up until delivery prospectively and the perinatal outcomes of the patients were recorded.

Results: Of 73 women included in the study, 36 women delivered within 7 days and 37 women delivered beyond 7 days after admission. The maternal serum calponin 1 level was significantly high in women who delivered within 7 days (p: 0.031). The threshold value of 2?ng/mL for maternal serum calponin 1 predicted delivery within 7 days with 61.1% sensitivity and 62.2 specificity (area under curve, 0.658, confidence interval 0.53–0.79). The general accuracy values for maternal cervical length measurement (≤25?mm), serum calponin 1 level (>2?ng/mL) and the combination of two tests to predict delivery within 7 days was found to be 64.4%, 61.6% and 72.1%, respectively.

Conclusions: The maternal serum calponin 1 level may be a useful biomarker in short-term prediction of preterm birth among pregnancies complicated with threatened preterm labor, in addition to cervical length measurement.     

Amniotic fluid cathepsin-G in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate the amniotic fluid cathepsin-G concentrations in women with preterm prelabor rupture of membranes (PPROM) based on the presence of the microbial invasion of the amniotic cavity (MIAC) and/or intra-amniotic inflammation (IAI).

Methods: A total of 154 women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid cathepsin-G concentrations were assessed by ELISA. MIAC was determined using a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥?745?pg/mL.

Results: Women with MIAC had higher amniotic fluid cathepsin-G concentrations than women without MIAC (with MIAC: median 82.7?ng/mL, versus without MIAC: median 64.7?ng/mL; p?=?0.0003). Women with IAI had higher amniotic fluid cathepsin-G concentrations than women without this complication (with IAI: median 103.0?ng/mL, versus without IAI: median 66.2?ng/mL; p?p?Conclusions: The presence of either microbial-associated or sterile IAI was associated with increased amniotic fluid cathepsin-G concentrations in pregnancies complicated by PPROM. Amniotic fluid cathepsin-G appears to be a potential marker of IAI.     

Targeted delivery at 34 versus 35 weeks in women with preterm prelabor rupture of membranes

Objective: To compare planned delivery at 34 versus 35 weeks for women with preterm prelabor rupture of membranes (PPROM).

Materials and methods: We performed a retrospective cohort study of singleton pregnancies with PPROM after 24 weeks delivered from 2006 to 2014. In 2009, an institutional practice change established 35 weeks as the target gestational age before induction of labor was initiated after PPROM. Demographic and outcome measures were compared for two cohorts: women delivered 2006–2008 – target 34 weeks (T34) and women delivered 2009–2014 – target 35 weeks (T35). The primary outcome was neonatal intensive care unit (NICU) admission.

Results: Of the 382 women with PPROM, 153 (40%) comprized the T34 cohort and 229 (60%) comprized the T35 cohort. Demographic characteristics were similar between groups. There were no differences between groups in gestational age at PPROM (31.0?±?3.3 weeks versus 31.2?±?3.1 weeks; p?=?.50) or maternal complications. The mean gestational age at delivery was earlier in the T34 group (31.8?±?3.2 weeks versus 32.4?±?2.7 weeks; p?=?.04). The median predelivery maternal length of stay (LOS) was 1?day longer in the T35 group (p?=?.03); the total and postpartum LOS were similar between groups (p?>?.05). There were no differences in the rate of NICU admission (T34 89.5% versus T35 92.1%; p?=?.38) or median neonatal LOS (T34 14 days versus T35 17 days; p?=?.15). In those patients who reached their target gestational age, both maternal predelivery LOS and total LOS were longer in the T35 group (p?>?.05). The frequency of NICU admission in those reaching their target gestational age was similar between groups (T34 83.37% versus T35 76.19%; p?=?.46).

Conclusions: A 35-week target for delivery timing for women with PPROM does not decrease NICU admissions or neonatal LOS. This institutional change increased maternal predelivery LOS, but did not increase maternal or neonatal complications.     

Pentraxin 3 in maternal circulation: An association with preterm labor and preterm PROM,but not with intra-amniotic infection/inflammation

Objective.?Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).

Study design.?This cross-sectional study included women in the following groups: (1) nonpregnant (n?=?40); (2) uncomplicated pregnancies in the first (n?=?22), second (n?=?22) or third trimester (n?=?71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n?=?49); (4) PTL and intact membranes who delivered at term (n?=?49); (5) PTL without IAI who delivered preterm (n?=?26); (6) PTL with IAI (n?=?65); (7) preterm PROM without IAI (n?=?25); and (8) preterm PROM with IAI (n?=?77). Maternal plasma PTX3 concentrations were determined by ELISA.

Results.?(1) Maternal plasma PTX3 concentrations increased with advancing gestational age (r?=?0.62, p?<?0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29?ng/ml vs. 5.98?ng/ml, p?=?0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women (p?<?0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations.

Conclusions.?The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm.     

Amniotic fluid clusterin in pregnancies complicated by the preterm prelabor rupture of membranes

Objective: The aim of this study was to evaluate clusterin concentrations in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of the microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI) and microbial-associated IAI.

Methods: One hundred thirty-six women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid clusterin concentrations were assessed by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration?≥745?pg/mL. Microbial-associated IAI was characterized as the presence of both MIAC and IAI.

Result: Women with MIAC, IAI and microbial-associated IAI had lower amniotic fluid clusterin concentrations than women without these complications (with MIAC: median 1314?ng/mL versus without MIAC: median 1633?ng/mL, p?=?0.003; with IAI: median 1281?ng/mL versus without IAI: median 1575?ng/mL, p?=?0.04; with microbial associated-IAI: median 1220?ng/mL versus without microbial-associated IAI: median 1575?pg/mL; p?=?0.008). A week negative correlation between amniotic fluid clusterin concentrations and gestational age at sampling was revealed (rho=??0.30; p?=?0.0005).

Conclusions: The presence of MIAC, IAI and microbial-associated IAI was characterized by lower amniotic fluid clusterin concentrations in pregnancies complicated by PPROM.     

Umbilical cord blood concentration of soluble scavenger receptor for hemoglobin,but not pentraxin 3, is of value for the early postpartum identification of the presence of histological chorioamnionitis

Objective: To determine whether umbilical cord blood concentrations of soluble scavenger receptor for hemoglobin (sCD163) and pentraxin 3 (PTX3) are of value in the early postpartum diagnosis of histological chorioamnionitis in preterm prelabor rupture of membranes (PPROM). Methods: Eighty-three women with pregnancies complicated by PPROM between 24 and 36 weeks of gestation with (n?=?38) and without (n?=?45) the presence of histological chorioamnionitis were included in the study. We compared umbilical cord blood sCD163 and PTX3 levels in preterm neonates from PPROM pregnancies with versus without the presence of histological chorioamnionitis using nonparametric test (Mann–Whitney U test). Results: The presence of histological chorioamnionitis was associated with a higher median umbilical cord blood sCD163, but not PTX3 concentration, to compare with the absence of histological chorioamnionitis [sCD163: median 1466?ng/mL, interquartile range (IQR) 1187–1828 vs. 1168?ng/mL, IQR 887–1595; p?=?0.01; PTX3: median 3.96?ng/mL, IQR 2.24–6.77 vs. 2.95?ng/mL, IQR 1.74–6.93; p?=?0.49]. Conclusions: HCA is associated with an increase of umbilical cord blood sCD163, but not PTX3 concentration. Umbilical cord blood sCD163 seems to be a postpartum marker of the presence of histological chorioamnionitis.     

C-reactive protein at 11–13 weeks’ gestation in spontaneous early preterm delivery

Objective: To examine the potential value of maternal serum level of C-reactive protein (CRP) in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of high-sensitivity CRP at 11–13 weeks’ gestation was measured in a case–control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks, with 15 cases presenting with contractions and 15 cases presenting with preterm premature rupture of membranes, and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum CRP in the two outcome groups was compared. Results: The median serum CRP MoM was not significantly different in the spontaneous early preterm delivery group compared to the term delivery group (1.101, IQR = 0.572–1.985 vs. 0.975, IQR = 0.577–1.923; p = 0.813). The prevalence of CRP MoM above the 75th percentile was not significantly different between the early preterm delivery group compared to the term delivery group (26.7 vs. 24.4%; p = 0.811). In the preterm delivery group, the median serum CRP MoM in those presenting with contractions was not significantly different from those presenting with PPROM (1.175, IQR = 0.403–2.122 vs. 1.027, IQR = 0.659–1.940; p = 0.713). High-sensitivity CRP did not significantly improve prediction for preterm delivery over regular CRP. Conclusions: Measurement of maternal serum CRP at 11–13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.     

The fetal inflammatory response in subgroups of women with preterm prelabor rupture of the membranes

Abstract

Objective: To evaluate the influence of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) on the intensity of the fetal inflammatory response and the occurrence of fetal inflammatory response syndrome (FIRS) in preterm prelabor rupture of membranes (PPROM).

Methods: One hundred and forty-nine women with singleton pregnancies complicated by PPROM between the gestational ages 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood interleukin (IL)-6 levels were evaluated using ELISA kits. The fetal inflammatory response was determined by IL-6 levels, and FIRS was defined as an umbilical cord blood IL-6 >11?pg/mL.

Result: IL-6 levels and the occurrence of FIRS were higher in women complicated with both MIAC and HCA (median IL-6 35.5?pg/mL, FIRS in 68%) than in women with HCA alone (median IL-6 5.8?pg/mL, FIRS in 36%), MIAC alone (median IL-6 2.8?pg/mL, FIRS in 17%) or women without MIAC or HCA (median IL-6 4.3?pg/mL, FIRS in 29%). There were no differences in IL-6 levels or rates of FIRS among women with MIAC alone or HCA alone and women without both MIAC and HCA.

Conclusion: A higher fetal inflammatory response mediated by umbilical cord blood IL-6 was identified when both MIAC and HCA were detected in pregnancies complicated by PPROM.     

Comparison of sVCAM-1 and sICAM-1 levels in maternal serum and vaginal secretion between pregnant women with preterm prelabour ruptures of membranes and healthy pregnant women

Objective: The study aims to evaluate the maternal serum and the vaginal fluid levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecular (sICAM-1) in pregnant women complicated by preterm prelabour ruptures of membranes (PPROM).

Materials and methods: The prospective case control study included 34 pregnant women with PPROM and 34 healthy pregnant women. Patients with additional diseases, a smoking habit and vaginal bleeding, as well as those using antibiotics, during the study period were not included in the study. Cervicovaginal fluid and serum samples were taken during the patients’ admission. The demographic data, maternal serum and vaginal fluid sVCAM-1 and sICAM-1, C reactive protein (CRP) and leukocyte counts were noted for all pregnant women included in the study. The sVCAM-1 and sICAM-1 levels were measured by enzyme-linked immunosorbent assay kits.

Results: In pregnant women with PPROM, the serum leukocyte (mean?±?SD =11.41?±?1.067 versus 9.18?±?1.56, p?p?p?=?.06), vaginal sVCAM-1 (median 208.00 versus 140.20?ng/ml, p?=?.014) and sICAM-1 (mean?±?SD 32.32?±?6.49?ng/ml versus 24.87?±?6.79?ng/ml, p?r?=?0.850; p?Conclusion: To the best of our knowledge, this is the first study evaluating the levels of sICAM-1 in maternal serum in pregnant women with PPROM. The maternal serum and vaginal fluid sVCAM-1 and sICAM-1 levels can be used as biochemical markers supporting the PPROM diagnosis because of the increase in both maternal serum and vaginal fluid sVCAM-1 and sICAM-1 levels in pregnant women with PPROM.     

The maternal thiol/disulfide homeostasis does not change in pregnancies complicated by preterm prelabor rupture of membranes

Purpose: To evaluate the maternal thiol/disulfide homeostasis in pregnant women complicated by preterm prelabor rupture of membranes (PPROM) and to compare the results with healthy pregnancies.

Materials and methods: This cohort study consisted of thirty-nine pregnancies complicated by PPROM and 44 gestational age-matched healthy pregnancies in the third trimester of gestation. Maternal serum samples were obtained at the day of diagnosis, and thiol/disulfide profiles were measured by using an automated assay method. The patients were followed till delivery, and perinatal outcomes were noted.

Results: The maternal native thiol (319.9?±?30.5?μmol/L versus 305.1?±?49.2?μmol/L, p: .100), total thiol (379.2?±?38.8?μmol/L versus 363.6?±?56.4?μmol/L, p: .142) and disulfide (29.7?±?11.7?μmol/L versus 29.3?±?10.1?μmol/L, p: .864) levels were similar between the groups. Maternal disulfide/native thiol, disulfide/total thiol and native thiol/total thiol ratios were similar between the groups (p: .610, p: .565 and .562, respectively). The maternal serum thiol/disulfide profiles were not significantly correlated with maternal serum C-reactive protein, white blood cell count values and ongoing pregnancy outcomes (p?>?.05).

Conclusions: The current study demonstrated that there was not any disturbance in maternal thiol/disulfide homeostasis in pregnancies complicated by PPROM at the time of initial diagnosis. Follow-up studies with larger sample size are needed to confirm our results.     

Amniotic fluid fetal hemoglobin in normal pregnancies and pregnancies complicated with preterm labor or prelabor rupture of membranes

Objective. Hemoglobin and its catabolic products have been associated with amniotic fluid (AF) discoloration and intra-amniotic infection/inflammation (IAI). However, the origin of AF hemoglobin (maternal or fetal) has not been determined. The aims of this study were to determine if fetal hemoglobin can be detected in AF obtained from normal pregnancies, and whether there is an association between AF fetal hemoglobin concentrations and gestational age, spontaneous labor (term and preterm), preterm prelabor rupture of membranes (PPROM) and IAI.

Study design. This cross-sectional study included pregnant women in the following groups: (1) mid-trimester (n = 60); (2) term not in labor (n = 21); (3) term in labor (n = 47); (4) spontaneous preterm labor with intact membranes (PTL) without IAI who delivered at term (n = 89); (5) PTL without IAI who delivered preterm (n = 74); (6) PTL with IAI (n = 78); (7) PPROM with (n = 48) and (8) without IAI (n = 48). AF fetal hemoglobin concentrations were determined by ELISA. Non-parametric statistics were used for analyses.

Results. (1) Fetal hemoglobin was detected in 80.4% of all AF samples; (2) women at term not in labor had a higher median AF fetal hemoglobin concentration than those at mid-trimester (p = 0.008); (3) labor at term was not associated with a significant difference in the median AF fetal hemoglobin concentration; (4) the median AF fetal hemoglobin concentration was not significantly different among the three PTL groups or between the PPROM groups; (5) women with PTL and IAI had a lower AF fetal hemoglobin percentage of the total hemoglobin than those without IAI who delivered preterm (p = 0.03) or at term (p < 0.001); (6) The median AF fetal hemoglobin concentration was higher in pregnancies complicated with PTL or PPROM than in women at term (p < 0.001 for all comparison).

Conclusions. (1) The concentration of immunoreactive AF fetal hemoglobin increases with gestational age; (2) the median AF fetal hemoglobin concentration is higher in pregnancies complicated with PTL or PPROM than in term pregnancies; (3) among women with PTL or PPROM, the AF fetal hemoglobin concentrations were not associated with IAI; (4) however, women with PTL and IAI had a lower percentage of AF fetal hemoglobin of the total hemoglobin than those without IAI, suggesting different mechanisms of disease.     

Intraamniotic inflammation and umbilical cord blood interleukin-6 concentrations in pregnancies complicated by preterm prelabor rupture of membranes

Objective: To evaluate umbilical cord blood interleukin (IL)-6 concentrations and the occurrence of fetal inflammatory response syndrome (FIRS) with respect to microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in pregnancies complicated by preterm prelabor rupture of membranes (PPROM).

Methods: One-hundred-eighty-eight women with singleton pregnancies complicated by PPROM between gestational ages of 24?+?0 and 36?+?6 weeks were included in the study. Blood samples were obtained by venipuncture from the umbilical cord after the delivery of the newborn. The umbilical cord blood IL-6 concentrations were evaluated using ELISA kits. FIRS was defined as umbilical cord blood IL-6?>?11?pg/mL.

Result: Women with MIAC and IAI had higher IL-6 concentrations than women without these complications (with MIAC: median 18.1?pg/mL versus without MIAC: median 5.8; p?<?0.0001; with IAI: median 32.9?pg/mL, versus without IAI: median 5.8; p?<?0.0001). Women with IAI with MIAC and women with IAI without MIAC had the highest umbilical cord blood IL-6 concentrations (medians: 32.6 and 39.4?pg/mL) and rates of FIRS (78% and 67%).

Conclusions: IAI was associated with the highest umbilical cord blood IL-6 concentrations and rate of FIRS independent of the presence or absence of MIAC.     

Maternal serum ferritin at 11- to 13-week gestation in spontaneous early preterm delivery

Objective: To examine the potential value of maternal serum level of ferritin in the first trimester of pregnancy in the prediction of spontaneous early preterm delivery. Methods: Maternal serum concentration of ferritin at 11–13-week gestation was measured in a case-control study of singleton pregnancies delivering phenotypically normal neonates, including 30 cases with spontaneous delivery before 34 weeks and 90 matched controls delivering after 37 weeks. The median multiple of the median (MoM) serum ferritin in the two outcome groups was compared. Results: The median serum ferritin MoM was not significantly different in the spontaneous early preterm delivery group compared with the term delivery group (1.143, interquartile range [IQR] 0.578–2.383 vs. 1.059, IQR 0.641–1.644, p = 0.725). Conclusions: Measurement of maternal serum ferritin at 11–13 weeks is unlikely to be useful in screening for spontaneous early preterm delivery.     

Cervical fluid calreticulin and cathepsin-G in pregnancies complicated by preterm prelabor rupture of membranes

Objective: The study aimed to determine the cervical calreticulin and cathepsin-G concentrations in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation (IAI).

Methods: Eighty women with singleton pregnancies complicated by PPROM were included in this study. Cervical and amniotic fluids were obtained at the time of admission, and concentrations of calreticulin and cathepsin-G in cervical fluid were determined using ELISA. The MIAC was defined as a positive PCR analysis for Ureaplasma species, Mycoplasma hominis, and/or Chlamydia trachomatis and/or by positivity for the 16S rRNA gene. IAI was defined as amniotic fluid bedside IL-6 concentrations ≥745?pg/mL

Result: Neither women with MIAC nor with IAI had different cervical fluid concentrations of calreticulin (with MIAC: median 18.9?pg/mL vs. without MIAC: median 14.7?pg/mL, p?=?0.28; with IAI: median 14.3?pg/mL vs. without IAI: median 15.6?pg/mL, p?=?0.57;) or of cathepsin-G (with MIAC: median 30.7?pg/mL vs. without MIAC: median 24.7?pg/mL, p?=?0.28; with IAI: median 27.3?pg/mL vs. without IAI: median 25.1?pg/mL, p?=?0.80) than women without those complications. No associations between amniotic fluid IL-6 concentrations, gestational age at sampling, and cervical fluid calreticulin and cathepsin-G concentrations were found.

Conclusions: Cervical fluid calreticulin and cathepsin-G concentrations did not reflect the presence of MIAC or IAI in women with PPROM.     

Correlation between spontaneous preterm birth and mid-trimester maternal serum estriol

Abstract

Objective: Elevated third trimester salivary estriol levels have been associated with preterm birth. We evaluated whether maternal estriol concentrations from second trimester serum correlated with preterm delivery.

Methods: A retrospective cohort study of 7767 patients evaluated with second trimester aneuploidy screening. Unconjugated serum estriol was measured by immunoassay, expressed as multiples of the median (MoM) for gestational age and evaluated for association with preterm (<37 week) birth.

Results: Elevated maternal serum estriol was significantly associated with preterm birth (1.15 MoM versus 1.03 MoM for delivery at term, OR 1.69 CI 1.41 to 2.02). 9.95% of spontaneously laboring patients <34 weeks had estriol MoM?>?2, as opposed to 6.23% of >34 week deliveries (p?=?0.031). There was a direct correlation between level of estriol concentrations and gestational age at time of delivery.

Conclusions: Elevated second trimester maternal serum unconjugated estriol is independently associated with a higher rate of spontaneous preterm birth.