Preterm Premature Rupture Of Membranes Group Research Articles

Evaluation of fetal cardiac output in preterm premature rupture of membranes.

We aimed to investigate fetal cardiac output (CO) in pregnancies with preterm premature rupture of membranes (PPROM) and its relationship with umbilical cord pH. This was a prospective study in total 90 pregnancies at 24-37weeks gestation including 42 pregnancies with PPROM and 48 that healthy controls. Fetal cardiac function including combined, left and right CO z-scores were compared. The neonates in the PPROM group were separated with umbilical cord pH above and below 7.25, and cardiac output was compared between groups. In PPROM group, CCO z-score, left cardiac output (LCO) z-score, and right cardiac output (RCO) were significantly lower compared to healthy pregnancies (p=.036, p=.001, p=.032, respectively), while RCO z-score showed no significant differences between the two groups. The aortic annulus and pulmonary artery annulus z-scores were measured smaller in the PPROM group (p=.000 and p=.001, respectively). In PPROM group, the fetal LCO z-score was significantly lower in neonates with an umbilical cord pH of 7.25 or less (p=.048). This study provides evidence that fetal CCO is lower in PPROM compared with healthy pregnancies. Reduced LCO z-scores may be useful for predicting adverse neonatal outcomes in pregnancies with PPROM.

A study on the level of NLRP3 inflammasome in patients with premature rupture of membranes.

In this study, we investigated the levels of interleukin-1β (IL-1β), IL-18, and the NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome in patients with premature rupture of membranes (PROMs). We selected 60 pregnant women at the Fourth Hospital of Baotou between January 2019 and July 2021. These women were divided into three distinct groups: the preterm PROM group with 20 cases, term PROM (TPROM) group with 20 cases, and a control group with 20 cases consisting of normal full-term pregnancies without PROM. Peripheral blood was collected from all participants. Using enzyme-linked immunosorbent assay, the levels of IL-1 and IL-18 in the plasma were assessed. Additionally, the proportions of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1-positive macrophages were also evaluated. The ratios of NLRP3, ASC, IL-1β, and IL-18 concentrations, along with the presence of caspase-1-positive macrophages, were notably greater in the PROM groups in comparison with the control group (p < .05). In the TPROM group and control group, the proportions of IL-1β and IL-18 levels were found to be lower than NLRP3, ASC, and caspase-1-positive macrophages levels (p < .05). The concentrations of IL-1β and IL-18, as well as the ratios of NLRP3, ASC, and caspase-1-positive macrophages, were elevated in patients with PROM compared to the control group. This suggests a potential correlation between the excessive activation of NLRP3 and the development of PROM.

Neutrophil/Lymphocyte and Platelet/Lymphocyte Ratio in Preterm Premature Rupture of Membranes.

This study aimed to investigate maternal hematological laboratory parameters of pregnancies complicated with preterm premature rupture of membranes (PPROM) compared to mothers of healthy-term infants (control group). This case-controlstudy included 158 mothers who were divided into PPROM (n=67) and control (n=91) groups, respectively. Laboratory parameters of platelet, lymphocyte, and neutrophil counts, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) were recorded at the time of diagnosis for the PPROM group and at the time of hospital admission for birth for the control group. NLR was significantly higher in the PPROM group than in the control group (p=0.001). The cutoff value of NLR to predict PPROM was 6.73 (AUC=0.671, 95% confidence interval=0.58-0.75,p=0.000). A cheap and routine NLR blood test can be used to predict PPROM before labor.

Risk of Neonatal Sepsis With Rescue Steroids in Preterm Premature Rupture of Membranes.

Objective To evaluate whether a rescue course of corticosteroids, when given at least 14 days after the initial course, is associated with an increased risk of neonatal sepsis after preterm premature rupture of membranes (PPROM). Methods We performed a retrospective, descriptive cohort study of women with singleton gestations from 23+0 to 34+0 weeks of gestation who received a rescue course of corticosteroids within the Indiana University Health Network from January 2009 through October 2016. Patients were separated into three groups based on amniotic membrane status at the time of each corticosteroid administration: Group 1 (intact membranes at initial/intact membranes at rescue), Group 2 (intact membranes at initial/PPROM at rescue), and Group 3 (PPROM at initial/PPROM at rescue). The primary outcome (neonatal sepsis) was compared between the groups. Patient characteristics and neonatal outcomes were analyzed with Fisher's exact test for categorical variables and ANOVA for continuous variables. Relative risk (RR) was calculated by comparing those with ruptured membranes to those with intact membranes at the time of rescue course administration. Results A total of 143 patients were eligible. Neonatal sepsis occurred in 6.8% of patients in Group 1, 21.1% of patients in Group 2, and 23.8% of patients in Group 3. Groups 2 and 3 had a statistically significant higher rate of neonatal sepsis than Group 1 (p = 0.021). The RR of neonatal sepsis after a rescue course in patients with PPROM (Groups 2 and 3) was 3.31 (95% CI = 1.32, 8.29) compared to those with intact membranes at the time of rescue course administration (Group 1). Conclusion A rescue course of corticosteroids in women with PPROM at the time of rescue administration was associated with an increased risk of neonatal sepsis. This increased risk was seen in women with intact membranes as well as ruptured membranes during their initial course of steroids. Larger studies are needed to further investigate this association.

Evaluation of Midkine levels in pregnant women with preterm premature rupture of membranes: A cohort study from a tertiary hospital.

To assess midkine (MK) levels in pregnant women with preterm premature rupture of membranes (PPROM) and compare them to healthy pregnant women. We also assessed the performance of the maternal serum MK level in predicting neonatal intensive care unit (NICU) requirement in the PPROM group. Forty pregnant women who presented to our clinic at 24-37 gestational weeks and were diagnosed with PPROM were included in the study group. During the same period, 40 healthy pregnant women at similar gestational weeks were randomly selected as the control group. Clinical characteristics, inflammatory markers, and serum MK levels were compared between the groups. The same parameters were then compared between the PPROM cases with and without NICU requirement. Finally, the receiver operating characteristic (ROC) analysis was performed to assess the predictive value of MK for NICU requirement. The PPROM and control groups were similar in terms of demographics. The MK level of the pregnant woman with PPROM was significantly higher than that of the controls. No statistically significant difference was found between the MK levels of the cases with and without NICU requirement in the PPROM group. In the ROC analysis, the optimal cut-off value of was found to be 0.287, at which it had 63 % sensitivity and 65 % specificity (area under the curve(AUC): 0.78, 95 % confidence interval(CI): 0.683-0.881, p<0.001) for the prediction of NICU requirement in cases with PPROM. In the same analysis performed for the prediction of PPROM, when the optimal cut-off value was taken as 0.298, MK had 56 % sensitivity and 60 % specificity (AUC: 0.65, 95 % CI: 0.522-0.770, p=0.037). Serum MK seems to be associated with complicated inflammatory processes leading to PPROM, and this novel marker has the potential to predict NICU requirement in PPROM cases.

Impact of preterm premature rupture of membranes and oligohydramnios on in-hospital outcomes of very-low-birthweight infants

Objective To analyze neonatal outcomes in very-low-birthweight (VLBW) infants depending on the presence of preterm premature rupture of membranes (PPROM), oligohydramnios, or both. Methods The electronic medical records of VLBW infants admitted during the study period, January 2013 to September 2018, were reviewed. Neonatal outcomes (primary outcome: neonatal death; secondary outcome: neonatal morbidity) were compared depending on whether the infant was affected by PPROM or oligohydramnios. Logistic regression analysis was performed to assess the association of PPROM and oligohydramnios with neonatal outcomes. Results Three hundred and nineteen VLBW infants were included: (1) 141 infants in the PPROM group vs. 178 infants in the non-PPROM group, and (2) 54 infants in the oligohydramnios group vs. 265 infants in the non-oligohydramnios group. The infants affected by PPROM were at significantly younger gestational ages at birth with lower 5-min Apgar scores than those not affected by PPROM. Histologic chorioamnionitis was significantly more frequent in the PPROM group than in the non-PPROM group. The proportions of small-for-gestational-age infants and infants affected by multiple births were significantly higher in the non-PPROM group. The median (interquartile range) PPROM latency and onset were 50.5 (9.0 − 103.0) h and 26.6 (24.1 − 28.5) weeks, respectively. Based on the logistic regression analysis assessing the association of PPROM and oligohydramnios with the significant neonatal outcome, oligohydramnios was significantly associated with neonatal death (odds ratio [OR] = 2.831, 95% confidence interval [CI] 1.447 − 5.539), air leak syndrome (OR = 2.692, 95% CI 1.224 − 5.921), and persistent pulmonary hypertension (PPH) (OR = 2.380, 95% CI 1.244 − 4.555). PPROM per se was not associated with any neonatal outcome. However, early onset PPROM and prolonged PPROM latency were associated with neonatal morbidity and mortality. When PPROM was accompanied by oligohydramnios, it was associated with increased odds for PPH (OR = 2.840, 95% CI 1.335 − 6.044), retinopathy of prematurity (OR = 3.308, 95% CI 1.325 − 8.259), and neonatal death (OR = 2.282, 95% CI 1.021 − 5.103). Conclusion PPROM and oligohydramnios affect neonatal outcomes differently. Oligohydramnios, but not PPROM, is a significant risk factor for adverse neonatal outcomes, which is presumably related to pulmonary hypoplasia. Prenatal inflammation appears to complicate neonatal outcomes in infants affected by early PPROM and prolonged PPROM latency.

Neonatal outcomes in women with preterm premature rupture of membranes at periviable gestational age

To examine the outcomes of preterm infants born to women with preterm premature rupture of membranes (PPROM) at periviable gestational age. This is an observational retrospective cohort study analyzing data collected on singleton deliveries complicated by prolonged premature rupture of membranes occurring between 17 and 33 weeks of gestation. Neonatal outcomes including birth weight, Apgar score, retinopathy of prematurity, intraventricular hemorrhage, bronchopulmonary dysplasia, necrotizing enterocolitis, hearing impairment and mortality were evaluated. Ninety-four preterm infants who were born after a prolonged premature rupture of membranes of at least 7 days were included in the study. Median gestational week at onset of membrane rupture was 27.1 ± 4.2 weeks (range 17–33) and median latency period in days was 16 ± 21.8 (range 7–105). The cohort was stratified by gestational week (GW) at onset of PPROM (group 1: 17–23, group 2: 24–27, and group 3: 28–33). We found that the survival rate to discharge within neonates born after prolonged rupture of membrane at gestational week less than 24 weeks is 79.2% and 88.9% in group 2. These neonates did not show an increased rate of major morbidities compared to neonates born following membrane rupture at gestational week 24 to 27. We described a high survival rate to discharge without major morbidities following prolonged preterm membrane rupture of at least 7 days of latency before viability.

Association between Preterm Premature Rupture of Membranes and Vitamin D Levels in Maternal Plasma and Umbilical Cord Blood of Newborns: A Prospective Study

Background: Preterm premature rupture of membranes (PPROM) is a major cause of preterm birth. There are few reports on vitamin D deficiency associated with PPROM. We aimed to investigate the association between PPROM and vitamin D levels in maternal plasma and the umbilical cord blood of newborns. Methods: This prospective study included 355 pregnant women who delivered live infants between March 2017 and December 2018 at a medical center. Vitamin D levels were measured in the maternal plasma at the first, second, third trimesters of pregnancy and just before delivery, and in the umbilical cord blood of newborns at birth. In addition, we evaluated the pregnancy and neonatal outcomes according to vitamin D status. Results: The rate of PPROM in the vitamin D deficiency group (25(OH)D &lt;20 ng/mL) was higher than in the non-deficiency group (25(OH)D ≥20 ng/mL) (p = 0.003). Vitamin D levels were significantly lower in the PPROM group than non-PPROM group in maternal plasma [at the first (p = 0.020) and second trimesters (p = 0.029), just before delivery (p = 0.015)], and in the cord blood of newborns (p = 0.006). Multiple logistic regression analysis showed that the odds ratio of PPROM by the increase of 1ng/mL of vitamin D levels in the cord blood of newborns was 0.907 (95% confidence interval 0.836–0.983) after adjustment for other confounders (age, gravidity, parity, and body mass index). Conclusions: Vitamin D deficiency has a significant association with PPROM. Our study would aid in understanding the mechanism of prevention of PPROM associated with vitamin D deficiency as well as reduction in preterm births.

Fetomaternal Outcomes in Women Affected With Preterm Premature Rupture of Membranes: An Observational Study From a Tertiary Care Center in Eastern India

Introduction: Preterm premature rupture of membranes (PPROM) is the spontaneous rupture of the fetal membranes before the completion of 37 weeks of pregnancy. PPROM occurs in 3% of pregnancies.Methodology: This prospective observational study was conducted between September 2019 and March 2021, involving 150 antenatal patients attending our outpatient department or labor room. All pregnant women with a singleton pregnancy between 28 and 37 weeks of gestational age with PPROM were included in our study.Results: A total of 44% of women were admitted to the hospital within 6-11 hours of the onset of PPROM, while 34% of women were admitted within five hours and 15.33% were admitted within 12-23 hours of the onset of PPROM. The most common organisms isolated in high vaginal swabs were Enterococcus faecalis (18%), Escherichia coli (12%), Staphylococcus aureus (12.66%), Staphylococcus haemolyticus (6.66%), and Candida albicans (4.66%). Around 74.66% of women were delivered within 24 hours of the onset of PPROM, whereas only 2.6% of patients were delivered after 72 hours and the rest 34% were delivered between 25 and 72 hours. Of our study subjects, 10% were febrile, 4% were having urinary tract infections, 2.5% had postpartum hemorrhage, and 2% had chorioamnionitis. As far as neonatal morbidity and mortality are concerned, birth asphyxia and jaundice were seen in 12% of patients each, whereas septicemia was found in 4% of study subjects.Conclusion: Owing to the association of higher maternal and perinatal morbidity and mortality, cases, especially in the early PPROM group, should be strictly monitored for clinical and laboratory signs of chorioamnionitis while opting for conservative management.

Expression and role of anti-oxidative damage factors in the placenta of preterm infants with premature rupture of membranes.

To study the association of the anti-oxidative damage factors nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) with preterm premature rupture of membranes (PPROM). A prospective study was conducted. The neonates who were hospitalized in Yanbian Hospital from 2019 to 2020 were enrolled as subjects, among whom there were 30 infants with PPROM, 32 infants with term premature rupture of membranes (TPROM), and 35 full-term infants without premature rupture of membranes (PROM). Hematoxylin and eosin staining was used to observe the inflammatory changes of placental tissue. Immunohistochemical staining was used to measure the expression of Nrf2, HO-1, and NQO1 in placental tissue. Western blot was used to measure the protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue. Compared with the PPROM group, the TPROM group and the non-PROM full-term group had significantly higher positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue (P<0.05). There were no significant differences in the positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue between the TPROM and non-PROM full-term groups (P>0.05). The low expression levels of Nrf2, HO-1, and NQO1 in placental tissue may be associated with PPROM, suggesting that anti-oxidative damage is one of the directions to prevent PPROM.

Measurement of the Uterocervical Angle for Predicting the Latent Period in Pregnancy Exhibiting Premature Membrane Rupture

Objectives: The duration of the latent period is uncertain in preterm premature rupture of membranes (PPROM). This time estimate provides information on the time of the corticosteroid to be applied and the time of delivery of the pregnant women. Here, we used transvaginal sonography to determine the relationship between the uterocervical angle (UCA) and PPROM latency and the risk for neonatal complications. Design: This is a prospective cohort study of 80 singleton pregnancies with PPROM. Participants/Materials, Setting, and Methods: This prospective cohort study was conducted at a tertiary center with a total of 80 singleton pregnancies with PPROM. The UCA and cervical length were measured in the first evaluation of PPROM in patients between 24 and 34 weeks of age. The study population was subdivided into 2 groups: group 1 (n = 27) included women who gave birth within 10 days after a PPROM diagnosis and group 2 (n = 53) included women who gave birth later than this. Our aim was latency prediction (more or less than 10 days) in PPROM patients undergoing regular UCA monitoring. Results: Of the women in group 1, 74.1% (n = 20) had spontaneous births and 7.4% (n = 2) had induced births because of clinical chorioamnionitis. Of the women in group 2, 71.6% (n = 38) had spontaneous births and 7.6% (n = 4) had induced births because of clinical chorioamnionitis (n = 3) or poor fetal condition (n = 1). We drew receiver operating characteristic curves to explore whether the UCA predicted birth within 10 days of PPROM. The area under the curve was 0.894 (p < 0.001). The optimal UCA cutoff was 108°, with 93% sensitivity and 85% specificity. Limitations: First, the sample size was small; it would have been better to have more patients. Second, we measured the UCA only once. Third, patients were not categorized by parity. Conclusions: The UCA, measured by the transvaginal route, can successfully predict latent period in PPROM. Measuring the UCA can be useful to determine the time of corticosteroid administration and to inform patients about the time of birth.

Inflammasome components and ADAMTS4 in premature rupture of membranes.

Inflammation may be responsible for the development of premature rupture of membranes (PROM) including preterm PROM (PPROM) and mature PROM (MPROM). A total of four classic receptor proteins have been confirmed to assemble inflammasomes: NLR family pyrin domain containing (NLRP)1, NLRP3 and NLR family CARD‑domain containing4(NLRC4) and absent in melanoma2(AIM2). The activation and expression of these receptor‑modulated inflammasomes in placenta and fetal membrane of PROM pregnancies requires investigation. In addition, a disintegrin and metalloproteinase with thrombospondin motifs4(ADAMTS4) is a risk factor for PROM, but whether its expression is associated with inflammasome activation remains to be elucidated. In the present study, the placenta and fetal membrane tissues of patients who had suffered PPROM and MPROM and healthy pregnancies were investigated. Reverse transcription‑quantitative PCR was used to determine the mRNA expression of inflammasomes and ADAMTS4. Western blotting, immunohistochemistry and ELISA were used to investigate the protein expression levels of inflammasomes and ADAMTS4. The results demonstrated that all four inflammasomes were elevated in placenta and fetal membrane of PPROMs as were mRNA and protein expression levels of IL‑18 and IL‑1β (compared with controls). A further increase of inflammasomes and interleukins was observed in MPROMs compared with controls. Similar results were also observed in ADAMTS4 expression in PPROM and MPROM groups. However, immunohistochemistry results revealed no significant difference of inflammasome receptor expression in PPROMs compared with controls. Finally, a general positive correlation between ADAMTS4 and all four inflammasome receptors in placenta and fetal membrane of PPROMs and MPROMs was observed. The present study revealed that NLRP1, NLRP3, AIM2 and NLRC4 inflammasome activation in PROM was increased. Promoted ADAMTS4 level was further observed in PROM group and was significantly correlated with inflammasome expression. Inhibition of inflammasome activation may provide a therapeutic target for clinical PROM treatment.

The Importance of Clinical Presentation in Risk and Management of Recurrent Preterm Birth.

This study aimed to compare the risk of recurrent spontaneous preterm birth (sPTB), as well as cerclage efficacy, between groups stratified by phenotype of the index sPTB. This is a retrospective cohort study of women with a history of sPTB. Included were women with a history of singleton sPTB who received progesterone in a subsequent pregnancy. Multifetal gestations and abdominal cerclage were excluded. Exposure groups were based upon the presenting symptom that preceded their first sPTB and included painless cervical dilation (PCD), preterm premature rupture of membranes (PPROM), and painful dilation (preterm labor [PTL]). Primary outcome was delivery <34 weeks in a subsequent pregnancy. Secondary outcomes included delivery <28 and <37 weeks. Rates were compared using the Chi-square test. Multivariable Poisson regression was used to adjust for confounders. A total of 723 women were included. A total of 114 (16%) presented with PCD, 305 (42%) with PPROM, and 304 (42%) with PTL in their first sPTB. Cerclage in subsequent pregnancy was highest in the PCD group (42%) when compared with the PPROM (16%) and PTL (12%) groups. Rates of sPTB <34 and 37 weeks were similar among the groups. After adjusting for confounders, PCD was found to significantly increase the risk of recurrent sPTB <28 weeks (incidence rate ratio: 3.46 [1.09-11.0]; p = 0.04). Of the 121 women who underwent cerclage, there were no significant differences in rates of sPTB between the clinical presentation groups. PCD as a specific phenotype of sPTB impacts recurrence of delivery before 28 weeks, but not at later gestational ages. In contrast, there was no significant association between clinical presentation of index sPTB and gestational latency in women who also underwent cerclage placement in a subsequent pregnancy. Our data suggest that clinical presentation is important with regards to recurrence of early sPTB, but not sPTB at later gestational ages. · Phenotype is critical to understanding PTB.. · Phenotype is associated with recurrent PTB.. · Painless dilation is associated with recurrent PTB..

Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes

Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2–4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.

Can vitamin C and interleukin 6 levels predict preterm premature rupture of membranes: evaluating possibilities in North Indian population.

ObjectiveWe aimed to evaluate the relation between plasma ascorbic acid levels and the occurrence of preterm premature rupture of membranes (PPROM) and whether patients with ascorbic acid deficiency have predisposition to microbial invasion, as revealed by serum interleukin-6 (IL-6) levels and confirmed by placental culture sensitivity evaluation.MethodsThis controlled study involved 50 women with PPROM at gestational age between 28 and 36.6 weeks. Fifty patients with uncomplicated pregnancy and intact membranes were observed as control group. Serum ascorbic acid and IL-6 levels were evaluated for PPROM group subjects and controls, matched by their gestational age and body mass index. Repeat samples for IL-6 were taken after 48 hours of admission in PROM group subjects and at the onset of labor in controls. Placental membranes were sent for culture sensitivity evaluation after delivery.ResultsThe mean plasma level of ascorbic acid was 0.60±0.35 mg/dL and 1.18±0.43 mg/dL in the PPROM and control groups, respectively, showing significant difference. Plasma IL-6 level rose from 18.18±5.94 pg/mL to 34.32±7.31 pg/mL after 48 hours of admission in the PPROM group (P=0.000). Plasma IL-6 level in controls rose from 5.59±4.36 pg/mL at admission to 7.36±3.67 pg/mL at the onset of labor. Membrane culture test results were positive in a total of 40 samples, of which 37 samples were from the PPROM group subjects.ConclusionVitamin C deficiency, when complemented with elevated serum IL-6 level, can predict susceptibility to PPROM in the third trimester; the risk increases in women with prior history of similar pathology.

Regulation of Keap-1/Nrf2 Signaling Pathway Is Activated by Oxidative Stress in Patients with Premature Rupture of Membranes

BackgroundThe potential mechanisms underlying premature rupture of membrane (PROM) is still unknown. The aim of this study was to determine the role of Keap-1/Nrf2 signaling pathway activation by oxidative stress in patients with preterm premature rupture of membranes.Material/MethodsPlacental tissues from preterm premature rupture of membranes (PPROM) (n=20), full-term premature rupture of membranes (FPROM) (n=20), and normal-term births (n=20) were collected and amniotic tissues were separated from the placental tissues from pregnant women at Shandong Provincial Qianfoshan Hospital. RT-PCR and Western blot were used to detect the levels of factors in the Keap-1/Nrf2 signaling pathway. To investigate the roles of Nrf2, we downregulated Nrf2 expression using siRNA in primary human amniotic epithelial (HAE) cells.ResultsAmong the control group, FPROM group, and PPROM group, the reactive oxygen species (ROS) levels were significantly increased in the FPROM and PPROM groups. The differences indicated higher levels of oxidative stress in amniotic tissues with FPROM and PPROM after downregulation of si-Nrf2 in HAE cells. Antioxidants were lower in amniotic tissues with the FPROM group and PPROM group than in the control group. The antioxidant enzymes catalase (CAT), glutathione (GSH), glutathione peroxidase (GSHPx), and superoxide dismutases (SOD1 and SOD2) were examined in amniotic tissues. We found that the ROS levels were significantly increased after downregulation of si-Nrf2 compared with the control group. We found that the expression of Heme Oxygenase-1 (HO-1) and Glycogen Synthase Kinase-3b (GSK-3b), which is critical in the Keap-1/Nrf2 signaling pathway, increased significantly after downregulation of si-Nrf2 in HAE cells.ConclusionsWe found that increased ROS levels and decreased antioxidant enzymes in the PPROM and FPROM patients compared with the control group.

The effects of latency period in PPROM cases managed expectantly

Objective: Preterm premature rupture of membranes (PPROM), associated with prematurity, is an important obstetric complication that may cause neonatal mortality and morbidity. The optimal delivery time is controversial in cases with the expectant approach. The fetal effects of long-term exposure to PPROM are unknown. This study aimed to evaluate the maternal and fetal outcomes of expectantly-managed PPROM cases with different latency periods at 240/7–346/7 weeks of gestation.Material and method: The study group consisted of 206 patients at 240/7–346/7 weeks of gestation who met the inclusion criteria. Patients were divided into three groups according to their weeks of PPROM diagnosis as 240/7−286/7, 290/7−316/7, and 320/7−346/7. The period from membrane rupture to delivery was defined as the latency period and divided into three subgroups as 3–7 days, 8–13 days and ≥14 days. In addition to the demographic characteristics of the patients, maternal and obstetric complications, primary and secondary neonatal outcomes were compared between the groups. Primary neonatal outcomes were determined in terms of pathological Apgar scores (<5 at minute 1, <7 at minute 5), requiring resuscitation, admission to Neonatal Intensive Care Unit (NICU) and NICU length of stay. Secondary neonatal outcomes were determined in terms of respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, periventricular leukomalacia, and neonatal sepsis. In addition, for the prediction of morbidity and mortality, newborns were evaluated by SNAPPE II (Score for Neonatal Acute Physiology with Perinatal extension-II) consisting of the combination of biochemical and physiological parameters, using the parameters including mean blood pressure (mm/Hg), corporal temperature (°C), PO2/FiO2 ratio, lowest serum pH, multiple seizures, urine output (ml/kg/hr), Apgar score, birth weight, and small for gestational age. The higher the score of SNAPPE II, the higher the morbidity and mortality risk of neonates. For the statistical analysis, the Kruskal Wallis and one-way ANOVA tests were utilized for the numerical data. Categorical data were compared using the chi-square test. The receiver operating characteristic (ROC) test was used to determine the threshold value of the data affecting neonatal morbidity.Results: The mean PPROM week was found to be 29.7 ± 3.0 weeks and the mean delivery week was 31.8 ± 2.5 weeks. The mean latency period for all the patients was 15.1 ± 13.8 days. Clinic chorioamnionitis was observed in 17% of the cases. The lowest chorioamnionitis rate (8.6%) was in the 3–7-day latency period group. Total complications were significantly lower in the 290/7–316/7 week PPROM group in which the latency period was ≥14 days, compared to those in 3–7 days and 8–13 days (p = .001). Total complications were lower in the < 32 weeks PPROM groups in which the latency period was ≥14 days compared to those obtained in 3–7 days and 8–13 days. There was no significant difference between the latency period and total complications after 32 weeks (p = .422). The best discriminative cutoff value of SNAPPE-II for neonatal morbidity was 11.0 (sensitivity 82%, specificity 80%). In the present study, the optimal latency period for the best neonatal outcomes was found to be 34.5 days (sensitivity 70% and specificity 84%) between weeks 240/7–286/7, and 11.0 days between weeks 290/7–316/7 (sensitivity 68% and specificity 85%).Conclusions: Our findings indicated that a long latency period did not increase neonatal morbidity and there was no increase in neonatal complications after 32 weeks of the gestational period compared to those obtained before 32 weeks.

How do platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio change in women with preterm premature rupture of membranes, and threaten preterm labour?

The aim of the study was to investigate peripheral blood platelets, neutrophils and lymphocytes counts in women with preterm premature rupture of membranes (PPROM) and threatened preterm labour (TPL) compared with gestation-matched controls in order to learn how they change. This study was conducted on 60 women with PPROM, 50 women with TPL and 47 healthy pregnant women. Laboratory parameters (including complete blood count, C-reactive protein (CRP)) of all the participants were recorded. The neutrophil-to-lymphocyte ratio (NLR) values were significantly higher in PPROM group than TPL group and healthy control group (6.1 ± 3.9, 4.4 ± 1.7, 4.4 ± 2.2, p = .007, p = .018, respectively). At a cut-off level of 5.14, NLR accurately predicted occurrence of neonatal sepsis (AUC = 0.717 (95% confidence interval 0.610–0.824), p = .001) with sensitivity and specificity rates of 69.7% and 72.0%, respectively. In the management of the patients with PPROM, NLR can be used as a more cost-effective method than other blood parameters that require the use of a kit.IMPACT STATEMENTWhat is already known on this subject? There is only one study in the literature evaluating blood count parameters (such as platelet-to-lymphocyte ratio (PLR), NLR) in PPROM pregnancies. That study demonstrated PLR and NLR were both higher in the PPROM group.What do the results of this study add? The present study demonstrates that only NLR is higher in the PPROM group. Furthermore, we have also demonstrated distinctively that NLR can predict occurrence of neonatal sepsis.What are the implications of these findings for clinical practice and/or further research? High values of NLR may be useful for predicting adverse outcomes in PPROM and TPL patients as a cost-effective method. Further studies are needed to determine whether these parameters can be used to predict if a pregnant woman who is at risk of preterm labour will result in adverse perinatal outcome.

Phenotypic overlap in neonatal respiratory morbidity following preterm premature rupture of membranes versus spontaneous preterm labor

Background Bronchopulmonary dysplasia (BPD), a major source of morbidity in premature neonates, has been associated with intrauterine infection and preterm birth. Both preterm premature rupture of membranes (PPROM) and spontaneous preterm labor (sPTL) are linked with intrauterine inflammation. Whether PPROM and sPTL, as two phenotypic categories of preterm birth, are associated with exposure to different degrees and durations of inflammation that might impact fetal lung development is unknown. PPROM may be associated with longer latency until delivery, which is beneficial for neonatal mortality, but may impart greater injury risk to the developing fetal lungs. It is unknown if PPROM is associated with a greater risk of adverse neonatal respiratory outcomes than sPTL. Objective The objective of this study was to determine if PPROM imparts a differentially greater risk for neonatal BPD than sPTL. A secondary objective was to determine if PPROM was associated with a greater risk of adverse neonatal respiratory outcomes other than BPD and whether gestational latency following PPROM or sPTL diagnosis constitutes a risk factor for fetal lung injury. Study design We conducted a retrospective secondary analysis of a large cohort of women at risk for spontaneous preterm birth, who were originally enrolled in a randomized controlled trial of magnesium sulfate versus placebo examining neuroprotection. For our study, we included women with a singleton pregnancy complicated by PPROM or sPTL and delivery between 24 and 34 weeks gestational age. Cases with multiple gestation, congenital anomalies, maternal seropositivity for human immunodeficiency virus, or hypertensive diseases of pregnancy (including preeclampsia) were excluded. The primary outcome was BPD. Secondary outcomes were respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN), requirement for mechanical ventilation, pneumonia, neonatal sepsis, fetal or neonatal death, and a composite of adverse neonatal respiratory outcomes including (BPD, pneumonia, RDS, and TTN). Statistical analyses included chi-square, Student’s t-test and logistic and multiple regression. Results A total of 1729 women were included in this analysis including 1554 with PPROM and 175 with sPTL. Women in the PPROM group were more likely to be older, not of Hispanic race, married, more educated, have smoked during pregnancy and have a greater body mass index. The BPD rate was not significantly different following PPROM versus sPTL. Neonates in the PPROM group experienced a lower rate of pneumonia (p = .001), neonatal sepsis (p = .009) and patent ductus arterious (PDA) requiring either medical or surgical therapy (p < .001) than neonates in the sPTL group. Chorioamnionitis was more common in the PPROM group (p = .008) than the sPTL group. After multivariable logistic regression with BPD or composite of adverse neonatal respiratory outcomes as the dependent outcomes, and controlling for gestational age at delivery, maternal smoking history, duration of mechanical ventilation and RDS, there was no significant difference between PPROM and sPTL. Conclusions BPD rates were not significantly different in neonates born to women following PPROM versus sPTL. However, PPROM was associated with lower rates of pneumonia, neonatal sepsis, and PDA requiring therapy in the univariate analysis, but not the multivariate analysis. Neonatal respiratory outcomes may have a similar phenotypic overlap regardless of whether preterm birth follows PPROM or sPTL.

Diagnostic value of five inflammatory markers for the subclinical chorioamnionitis in pregnancies with preterm premature rupture of membranes

Objective Chorioamnionitis in pregnancies with preterm premature rupture of membranes(PPROM) may lead to perinatal morbidity. There is no definite diagnostic method for detecting chorioamnionitis before delivery. In this retrospective study, the diagnostic value of five inflammatory markers, including white blood cell (WBC), neutrophil percentage (NEU), c-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) of subclinical chorioamnionitis in PPROM were investigated. Methods A total of 74 PPROM (Group A: 21 PPROM without infection; Group B: 43 PPROM with subclinical chorioamnionitis; Group C: 10 PPROM with chorioamnionitis) and 46 controls (Group D: normal full-term pregnancies) were recruited from the Third Affiliated Hospital of Army Medical University between 2013 and 2017. The five markers were measured within 24 hours before the delivery. The diagnostic value of inflammatory markers for subclinical chorioamnionitis were assessed by t test and ROC curve. Results The levels of WBC, NEU and IL-6 in group A were significantly higher than those in group D (T=5.412, Z=-3.312, T=2.798, all P<0.05). The levels of five inflammatory markers in group B and C were all significantly increased compare with group D(Zb=-5.797, Zb=-5.296, Zb=-5.116, Zb=-3.279, Zb=-4.36, Tc=7.732, Zc=-4.622, Zc=-4.591, Zc=-3.509, Zc=-4.387,all P<0.05). Group B CRP, IL-6 and PCT levels were significantly higher than those of group A(Z=-3.10, Z=-2.95, Z=-2.202, all P<0.05). All five markers of group C were significantly higher than those of group A(T=-5.285, Z=-2.536, Z=-3.819, Z=-3.228, Z=-3.719, all P<0.05). The levels of WBC, NEU and IL-6 in group C were significantly higher than those in PPROM group B(Z=-3.296, T=-2.738, Z=-3.501, all P<0.05). In terms of predictive capability of subclinical chorioamnionitis, the individual area under ROC curve (AUC) of CRP, IL-6, and PCT were 0.740, 0.671, and 0.728 corresponding to the optimal cutoff 10.3 mg/L, 5.995 pg/ml, and 0.055 ng/ml respectively. The sensitivity value were 39.5%, 60.5% and 74.4%, the specificity value were 100%, 85.7% and 61.9%.The area under the ROC curves of CRP+IL-6,CRP+PCT,IL-6+PCT and CRP+IL+6+PCT were 0.746, 0.805, 0.776 and 0.816. The sensitivity value were 51.2%, 74.4%, 81.4% and 62.8%, the specificity value were 95.2%,81%,66.7% and 90.5%. Conclusions The model (combined with PCT, CRP and IL-6) may be helpful for the diagnosis of the subclinical chorioamnionitis in PPROM. Combined diagnosis of two markers in PCT,CRP and IL-6 could be superior to single inflammatory marker. Combined diagnosis of three could be better,which may provide a reference for clinical diagnosis. Key words: Fetal membranes, premature rupture; Chorioamnionitis; C-reactive protein; Interleukin-6; Calcitonin