Maternal Outcomes Following Active vs. Expectant Management of Previable Preterm Pre-Labor Rupture of Membranes: A Meta-Analysis.

The diagnosis of previable preterm pre-labor rupture of membranes (PROM) is known to be associated with poor outcomes for both the mother and the fetus. Following previable preterm PROM, patients are generally offered either active management through the termination of the pregnancy or expectant management to increase the chances of fetal survival. It is difficult to counsel patients because there is a lack of data directly comparing maternal outcomes following active vs. expectant management. Using the data in the current literature, the goal of the present meta-analysis was to determine if there were any differences in terms of maternal risks when active versus elective management was chosen. PubMed, Google Scholar, EMBASE, and Scopus were searched. We found four studies accounting for a total of 506 patients. The risk ratio (RR) of chorioamnionitis in active vs. expectant management was 0.30 (with a 95% confidence interval, CI, of 0.09-1.02). The heterogeneity of the study results was 81% (I2). A sub-analysis of two included studies revealed an RR of postpartum hemorrhage in active vs. expectant management of 0.75 (95% CI 0.27-2.07) and an RR of maternal sepsis of 0.23 (95% CI 0.04-1.28). The heterogeneity of the study results for this sub-analysis was 68% (I2) for postpartum hemorrhage and 0% (I2) for maternal sepsis. Overall, there was no statistically significant difference in the risk of chorioamnionitis, postpartum hemorrhage, or maternal sepsis when active management was chosen over expectant management in previable preterm PROM at <24 weeks. The scarcity and the high heterogeneity of the available data likely contributed to the lack of statistical significance and calls for further work directly comparing maternal outcomes following active vs. expectant management.

Evaluation and Management of Premature Rupture of Membranes: A Review Article.

Premature rupture of membranes (PROM), now also referred to as "pre-labour rupture of membranes," is the rupture of gestational membranes after 37 weeks but before the process of labour begins. When membrane rupture occurs before 37 weeks of gestation, it is referred to as preterm PROM (PPROM). Prematurity is held accountable for the majority of newborn morbidity and mortality. PROM causes around one-third of all preterm deliveries and complicates 3% of pregnancies. Significant morbidity and mortality rates have been associated with PROM. Preterm (PROM) pregnancies are more difficult to manage. Pre-labour rupture of membranes is characterised by its short latency, higher intrauterine infection risk, and greater umbilical cord compression probability. Women with preterm PROM are more likely to develop chorioamnionitis and placental abruption. Various diagnostic modalities include sterile speculum examination, the nitrazine test, the ferning test, and the latest advances, which are the Amnisure test and the Actim test. Despite all these tests, there is still a need for newer, non-invasive, rapid, and accurate tests. Admission to a hospital, amniocentesis to rule out infection, and, if necessary, prenatal corticosteroids and broad-spectrum antibiotics are all alternatives for treatment. As a result, the clinician managing a pregnant woman whose pregnancy has been affected by PROM plays a crucial role in the management and must be well aware of probable complications and control measures to reduce risks and increase the likelihood of the required outcome. PROM's proclivity for recurrence in later pregnancies provides a chance for prevention. Furthermore, prenatal and neonatal care developments will continue to enhance the outcomes of women and their children. The purpose of this article is to summarise the concepts related to the evaluation and management of PROM.

Preterm Labor and Preterm-PROM at a Lower Gestational Age Are Associated with a Longer Latency-to-Delivery Even in Patients with the Same Intensity of Intra-Amniotic Inflammation: "Carroll-Model" Revisited.

A previous study by Carroll et al. demonstrated that the time from preterm-PROM to delivery was longer at a lower gestational age (GA) when the membranes rupture, although the presence or absence of intra-amniotic inflammation (IAI) was not examined in that study. However, patients with either preterm labor (PTL) or preterm-PROM at a lower GA had more frequent IAI, which was associated with a shorter amniocentesis-to-delivery (ATD) interval as compared with inflammation-free amniotic fluid (AF). Up to now, there is no information about whether PTL and preterm-PROM at a lower GA are associated with a shorter or longer latency to delivery in cases with the same intensity of IAI. The objective of the study is to examine this issue. AF MMP-8 was measured in 476 singleton early preterm-gestations (21.5 < GA at amniocentesis < 34 wks) with PTL (n = 253) and preterm-PROM (n = 223). Patients were divided into three groups according to GA at amniocentesis (i.e., group-1: <26 wks; group-2: 26−30 wks; group-3: 30−34 wks). IAI was defined as an elevated AF MMP-8 (≥23 ng/mL), and IAI was classified into either mild IAI (AF MMP-8: 23−350 ng/mL) or severe IAI (AF MMP-8 ≥ 350 ng/mL). ATD interval was examined according to GA at amniocentesis in the context of the same intensity of IAI (i.e., inflammation-free AF, mild IAI, and severe IAI) among pregnant women with either PTL or preterm-PROM. IAI was more frequent at a lower GA in cases with PTL (group-1 vs. group-2 vs. group-3; 59.5% vs. 47.4% vs. 25.1%; X2test, p = 0.000034 and linear by linear association [LBLA], p = 0.000008) and in those with preterm-PROM (group-1 vs. group-2 vs. group-3; 69.2% vs. 50.0% vs. 32.0%; X2test, p = 0.000104, and LBLA, p = 0.000019). Of note, cases without IAI at a lower GA had a longer ATD interval in both PTL (Spearman's rank correlation test, γ = −0.360, p = 0.000003) and preterm-PROM (γ = −0.570, p = 0.000001) groups. Moreover, the lower the GA, the longer the ATD interval, even among patients with mild and severe IAI in both PTL (Spearman's rank correlation test; mild IAI, γ = −0.290, p = 0.039; severe IAI, γ = −0.299, p = 0.048) and preterm-PROM (mild IAI, γ = −0.565, p = 0.000013; severe IAI, γ = −0.363, p = 0.015) groups. In conclusion, PTL and preterm-PROM at a lower GA are associated with a longer latency to delivery, even in patients with the same intensity of IAI. This finding suggests that a more intense IAI may be needed for spontaneous preterm birth at a lower GA.

Maternal septicemia caused by Streptococcus mitis: a possible link between intra-amniotic infection and periodontitis. Case report and literature review.

BACKGROUND: Intra-amniotic infection has a strong causal association with spontaneous preterm birth and preterm prelabor rupture of membranes (PPROM). The most common route of intra-amniotic infection is the ascending pathway in which microorganisms from the vagina gain access to the amniotic cavity. Distant microorganisms such as those from the oral cavity have been reported in intra-amniotic infection through hematogenous spreading. CASE PRESENTATION: A 31-year-old gravida 1, para 0 Thai woman at 33+6 weeks' gestation presented with leakage of vaginal fluid and irregular uterine contraction. She developed fever at 4 h after admission and was later diagnosed with acute chorioamnionitis. A Cesarean section was performed to terminate pregnancy. In addition to a blood culture, the cultures of amniotic fluid, vaginal and chorioamniotic membrane swabs were positive for Streptococcus mitis with identical susceptibility profiles. After the delivery and antibiotic prescription, oral examination showed dental caries and chronic periodontitis. CONCLUSIONS: This is the first case report demonstrating maternal septicemia and intra-amniotic infection caused by S. mitis which might be attributed to periodontitis in women presenting with preterm PROM. We highlighted the association of periodontal disease and preterm labor/PROM syndrome. Oral cavity examination should be included in the prenatal care to ensure good dental hygiene.

Nonovert disseminated intravascular coagulation (DIC) in pregnancy: a new scoring system for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion.

BACKGROUND: Nonovert disseminated intravascular coagulation (DIC) is a subclinical hemostatic dysfunction that has not yet reached the decompensation stage. The detection of pregnant patients at this stage may assist in the identification of those who will develop severe obstetrical hemorrhage, as it is one of the leading causes for preventable maternal mortality. Currently, nonovert DIC is diagnosed by a scoring system based on nonpregnant patients, originally generated by the International Society on Thrombosis and Hemostasis (ISTH), which does not address the physiologic changes of the hemostatic system during pregnancy. OBJECTIVES: (1) To develop a pregnancy-specific nonovert DIC score, (2) to determine the diagnostic performance of this score in detecting women at risk for obstetrical hemorrhage requiring blood product transfusion, and (3) to compare it to the existing ISTH nonovert DIC score. STUDY DESIGN: This retrospective study has longitudinal and cross-sectional components and includes three steps: (1) characterization of the longitudinal changes in the components of modified ISTH nonovert DIC scores, including these parameters - fibrinogen, antithrombin III, protein C, prothrombin time (PT), platelets, thrombin-antithrombin (TAT) complex, and D-dimer - during gestation in a group of normal pregnancies (n = 50); (2) development of a pregnancy-specific nonovert DIC score in a cross-sectional design of high-risk (n = 152) and control (n = 50) pregnancies, based on the predictive performance of each analyte for the detection of women at risk for obstetrical hemorrhage requiring blood product transfusion and a logistic regression model; and (3) comparison between the diagnostic performance of the pregnancy-specific nonovert DIC score and the modified ISTH nonovert DIC score to detect, upon admission, women who are at increased risk for subsequent development of obstetrical hemorrhage requiring blood product transfusion. RESULTS: (1) The study cohort included 202 patients, of which 21 (10%) had obstetrical hemorrhage that required blood product transfusion and were considered to have nonovert DIC; (2) using the nonpregnant ISTH nonovert DIC score, 92% of the patients had a D-dimer concentration above the 0.5 mg/L threshold, and only 2% were identified to have a low fibrinogen concentration (<100 mg/dL); thus, this scoring system was unable to identify any of the patients with nonovert DIC based on the suggested cutoff of a score of ≥5; (3) the parameters included in the pregnancy-specific nonovert DIC score were selected based on their contribution to the performance of the model for the prediction of women at risk for obstetrical hemorrhage requiring blood product transfusion; as a result, we excluded the PT difference parameter from the score and the TAT complex concentration was added; and (4) a pregnancy-specific nonovert DIC score of ≥3 had a sensitivity of 71.4% and a specificity of 77.9% to identify patients at risk for obstetrical hemorrhage requiring blood product transfusion. CONCLUSION: We propose (1) a pregnancy-specific nonovert DIC score adjusted for the physiologic changes in the hemostatic system during gestation; and (2) that the pregnancy-specific nonovert DIC score can be a useful tool for the identification of patients at risk for obstetrical hemorrhage requiring blood product transfusion.

Retrospective study of the recurrence risk of preterm birth in Japan.

BACKGROUND: A history of preterm birth is a risk factor for preterm birth in a future pregnancy, and there are some reports of prevention methods, such as the administration of progesterone. However, the rate of recurrence of preterm birth in Japan has not been clarified, and there is no data for judging whether these preventive methods are effective. OBJECTIVE: To clarify the risk of recurrence of preterm birth and preterm prelabor rupture of membranes (pPROM) in Japan. MATERIALS AND METHODS: A retrospective study was conducted using the perinatal registration database of the Japan Obstetrics and Gynecology Society for the Perinatal Center from 2014 to 2016. There were 704,418 subjects, of which 190,990 were excluded those with unknown maternal information, those under the age of 20 years, those with perinatal disease related to preterm birth, and first-time mothers. RESULTS: Logistic model unavailable and multivariate analysis were performed. An analysis of the preterm birth history indicated the risk of preterm birth in the current pregnancy, and the odds ratio for preterm birth recurrence once, twice, and three times or more was 3.3, 6.6, and 7.8, respectively. As a secondary analysis, we analyzed whether the history of pPROM is a risk factor of recurrence of pPROM and found a significant association with an odds ratio of 3.4. CONCLUSION: Having a preterm birth history increases the risk of recurrence of preterm birth, and the risk of recurrent preterm birth increases as the number of preterm births increases. Although this report is intended for high-risk pregnancies wherein the rate of preterm birth is high, as previously reported, our data indicate that in Japan, preterm birth is a risk factor of recurrent preterm birth.

Identifying the associated factors with onset of preterm PROM compared with term PROM - A retrospective cross-sectional study.

OBJECTIVE: To determine the risk factors associated with the preterm premature rupture of membranes (p-PROM). MATERIALS AND METHODS: This retrospective cross-sectional study assessed 110 p-PROM cases from among 6642 deliveries at a Japanese perinatal medical center, from June 2016 to September 2018. The control group comprised 220 term PROM (t-PROM) cases. We excluded cases with artificial PROM or rupture of membranes after labor, those with multiple pregnancies, those with p-PROM at 36 weeks and those with t-PROM at 37 weeks. In order to compare p-PROM with t-PROM, univariate and multivariate analysis were performed using several clinical factors at the time of PROM onset. RESULTS: The p-PROM group included 110 cases with 14-35 weeks PROM, and the t-PROM group included 220 cases with 38-41 weeks PROM. Eleven factors were identified as significant factors on the univariate analysis. A history of cervical conization (OR 37.5, 95% CI: 2.31-607.1), cervical length <25 mm at 28 weeks (OR 9.31, 95% CI: 1.76-49.3), negative Lactobacillus (OR 4.01, 95% CI: 1.18-13.7), and bleeding during the second trimester (OR 3.35, 95% CI: 1.18-9.53) were identified as significant factors by the multivariate analysis. Based on the risk factors identified during the multivariate analysis, we divided the 330 cases in the following three groups: 0 group (n = 244), 1 group (n = 60), and 2-4 group (n = 26). The ratio of p-PROM:t-PROM was calculated and compared for each group. The ratios were 21% (0 group), 57% (1 group), and 100% (2-4 group), indicating statistically significant differences between the groups (p < 0.001). CONCLUSION: We found that the following four factors were associated with p-PROM: history of cervical conization, cervical length <25 mm at 28 weeks, negative Lactobacillus, and bleeding during the second trimester. Our results suggest that we can identify patients who are at increased risk for p-PROM, based on these factors. Further research is necessary to determine the optimal treatment approach for these patients to prevent p-PROM.

The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications.

The fetus can deploy a local or systemic inflammatory response when exposed to microorganisms or, alternatively, to non-infection-related stimuli (e.g., danger signals or alarmins). The term "Fetal Inflammatory Response Syndrome" (FIRS) was coined to describe a condition characterized by evidence of a systemic inflammatory response, frequently a result of the activation of the innate limb of the immune response. FIRS can be diagnosed by an increased concentration of umbilical cord plasma or serum acute phase reactants such as C-reactive protein or cytokines (e.g., interleukin-6). Pathologic evidence of a systemic fetal inflammatory response indicates the presence of funisitis or chorionic vasculitis. FIRS was first described in patients at risk for intraamniotic infection who presented preterm labor with intact membranes or preterm prelabor rupture of the membranes. However, FIRS can also be observed in patients with sterile intra-amniotic inflammation, alloimmunization (e.g., Rh disease), and active autoimmune disorders. Neonates born with FIRS have a higher rate of complications, such as early-onset neonatal sepsis, intraventricular hemorrhage, periventricular leukomalacia, and death, than those born without FIRS. Survivors are at risk for long-term sequelae that may include bronchopulmonary dysplasia, neurodevelopmental disorders, such as cerebral palsy, retinopathy of prematurity, and sensorineuronal hearing loss. Experimental FIRS can be induced by intra-amniotic administration of bacteria, microbial products (such as endotoxin), or inflammatory cytokines (such as interleukin-1), and animal models have provided important insights about the mechanisms responsible for multiple organ involvement and dysfunction. A systemic fetal inflammatory response is thought to be adaptive, but, on occasion, may become dysregulated whereby a fetal cytokine storm ensues and can lead to multiple organ dysfunction and even fetal death if delivery does not occur ("rescued by birth"). Thus, the onset of preterm labor in this context can be considered to have survival value. The evidence so far suggests that FIRS may compound the effects of immaturity and neonatal inflammation, thus increasing the risk of neonatal complications and long-term morbidity. Modulation of a dysregulated fetal inflammatory response by the administration of antimicrobial agents, anti-inflammatory agents, or cell-based therapy holds promise to reduce infant morbidity and mortality.

Fetal inflammatory response is positively correlated with the progress of inflammation in chorionic plate.

INTRODUCTION: No information exists about the relationship among the progress of inflammation in chorionic-plate, fetal inflammatory response (FIR), funisitis, amnionitis and early-onset neonatal sepsis (EONS) in patients with either preterm labor or preterm premature rupture of membranes (preterm-PROM). The objective of current study is to examine this issue. METHODS: Study population included 247 singleton preterm gestations (21.6 weeks ≤ gestational age at delivery≤36 weeks) who had either preterm-labor or preterm-PROM with acute placental inflammation. We examined the intensity of FIR, and the frequency of fetal inflammatory response syndrome (FIRS), funisitis, amnionitis and proven or suspected EONS according to the progress of inflammation in chorionic-plate. The intensity of FIR was measured with umbilical cord plasma (UCP)-CRP concentration (ng/ml) at birth, and FIRS was defined as an elevated UCP-CRP concentration (≥200 ng/ml). The progress of inflammation in chorionic-plate was divided with a slight modification from previously reported-criteria as follows: stage-0, inflammation-free chorionic-plate; stage-1, inflammation restricted to subchorionic fibrin (SCF); stage-2, inflammation in the connective tissue (CT) of chorionic-plate without chorionic vasculitis; stage-3, chorionic vasculitis. RESULTS: 1) Stage-0, stage-1, stage-2 and stage-3 of inflammation in chorionic-plate were present in 36.8% (91/247), 29.6% (73/247), 25.5% (63/247), and 8.1% (20/247) of cases; 2) UCP-CRP concentration at birth was significantly and positively correlated with the progress of inflammation in chorionic-plate (Spearman's rank correlation test, P < .000001, γ = 0.391 and Kruskal-Wallis test, P < .001); 3) Moreover, FIRS, funisitis, amnionitis, and EONS were significantly more frequent as a function of the progress of inflammation in chorionic-plate. DISCUSSION: The intensity of FIR and the frequency of FIRS were positively correlated with the progress of inflammation in chorionic-plate in patients with either PTL or preterm-PROM. This suggests chorionic-plate may be an independent compartment for the analysis of inflammation.

Reducción embrionaria en embarazo gemelar / Embryo reduction in twin pregnancy

La reducción embrionaria es la interrupción selectiva del desarrollo de uno o varios fetos en el primer trimestre del embarazo. El embarazo gemelar se presenta aproximadamente en uno de cada 100 nacimientos y se considera como una entidad con alto riesgo materno y fetal. Los embarazos múltiples tienen un impacto mayor en los sistemas de salud, debido a la mayor frecuencia de complicaciones. La rotura prematura de membranas causa aproximadamente el 40 por ciento de los partos pretérmino y, como consecuencia, aportan un 10 por ciento de la mortalidad perinatal según la Sociedad Española de Ginecología y Obstetricia. En este caso clínico se observó que una actitud expectante con los pertinentes controles ecográficos (índice del líquido amniótico), analíticos (recuento leucocitario y reacción en cadena de la polimerasa) y clínicos (frecuencia cardiaca y temperatura) pueden llevar a una buena evolución posnatal que justificó al menos en esta ocasión, una actitud conservadora(AU)

Embryonic reduction is the selective interruption of the development of one or several fetuses in the first trimester of pregnancy. Twin pregnancy occurs in approximately one in every 100 births. It is considered an entity with high maternal and fetal risk. Multiple pregnancies have greater impact on health systems due to the higher frequency of complications. Premature rupture of membranes causes approximately 40 percent of preterm births and, consequently, it contributes 10 percent of perinatal mortality according to the Spanish Society of Gynecology and Obstetrics. In this clinical case it was observed that an expectant attitude with the relevant ultrasound (index of amniotic fluid), analytical (leukocyte count and polymerase chain reaction) and clinical (heart rate and temperature) controls can lead to good postnatal evolution, justified at least on this occasion, a conservative attitude(AU)

Human ß-defensin-1: A natural antimicrobial peptide present in amniotic fluid that is increased in spontaneous preterm labor with intra-amniotic infection.

PROBLEM: Human ß-defensins (HBDs) are antimicrobial peptides that participate in the soluble innate immune mechanisms against infection. Herein, we determined whether HBD-1 was present in amniotic fluid during normal pregnancy and whether its concentrations change with intra-amniotic inflammation and/or infection. METHOD OF STUDY: Amniotic fluid was collected from 219 women in the following groups: (a) midtrimester who delivered at term (n = 35); (b) term with (n = 33) or without (n = 17) labor; (c) preterm labor with intact membranes who delivered at term (n = 29) or who delivered preterm with (n = 19) and without (n = 29) intra-amniotic inflammation and infection or with intra-amniotic inflammation but without infection (n = 21); and (d) preterm prelabor rupture of membranes (pPROM) with (n = 19) and without (n = 17) intra-amniotic inflammation/infection. Amniotic fluid HBD-1 concentrations were determined using a sensitive and specific ELISA kit. RESULTS: (a) HBD-1 was detectable in all amniotic fluid samples; (b) amniotic fluid concentrations of HBD-1 were changed with gestational age (midtrimester vs term no labor), being higher in midtrimester; (c) amniotic fluid concentrations of HBD-1 were similar between women with and without spontaneous labor at term; (d) among patients with spontaneous preterm labor, amniotic fluid concentrations of HBD-1 in women with intra-amniotic inflammation/infection and in those with intra-amniotic inflammation without infection were greater than in women without intra-amniotic inflammation or infection who delivered preterm or at term; and (e) the presence of intra-amniotic inflammation and infection in patients with pPROM did not change amniotic fluid concentrations of HBD-1. CONCLUSION: HBD-1 is a physiological constituent of amniotic fluid that is increased in midtrimester during normal pregnancy and in the presence of culturable microorganisms in the amniotic cavity. These findings provide insight into the soluble host defense mechanisms against intra-amniotic infection.

Placental abruption: risk factors, management and maternal-fetal prognosis. Cohort study over 10 years.

OBJECTIVE: To describe maternal and fetal risk factors, diagnosis, management and prognosis of placental abruption (PA). STUDY DESIGN: A retrospective cohort study between January 2003 and December 2012 within the three maternity units of a French university hospital. We included 55,926 deliveries after 24 weeks' gestation including 247 cases of PA (0.4%). We conducted univariate analyses to compare PA and control groups. Multivariate models were constructed in order to study PA risk factors and perinatal morbidity and mortality. RESULTS: Independent risk factors for PA were preterm premature rupture of membranes (OR 9.5; 95% CI [6.9-13.1]), gestational hypertension (OR 7.4; 95% CI [5.1-10.8]), preeclampsia (OR 2.9; 95% CI [1.9-4.6]) and major multiparity (OR 1.6; 95% CI [1.1-2.4]). The classic clinical triad associating metrorrhagia, uterine hypertonia and abdominopelvic pains was present in only 9.7% of cases. Caesarean section rate was 90.3% with 51.8% being performed under general anesthesia. There was no case of maternal death, but maternal morbidity was considerable, with 7.7% of coagulation disorders and 16.6% of transfusion. After adjustment for the gestational age, we found an increased risk for pH≤7.0 (OR 14.9; 95% CI [9.2-23.9]) and neonatal resuscitation (OR 4.6; 95% CI [3.1-6.8]). Perinatal mortality was 15.8%, including 78% of fetal deaths. CONCLUSIONS: Appropriate multidisciplinary management can limit maternal morbidity and mortality but perinatal mortality, which occurs essentially in utero, remains high.

Preterm premature rupture of membranes without labor is not associated with increased levels of matrix metalloproteinase-9 protein.

OBJECTIVES: Preterm premature rupture of membranes (PROM) accounts for 30-40% of all preterm births. The objectives of this study were to determine whether matrix metalloproteinase-9 (MMP-9) is increased in preterm PROM fetal membranes, whether labor or gestational age affects expression, and whether the increase is localized to the rupture site or is membrane-wide. METHODS: Fetal membranes were collected from 15 pregnancies complicated by preterm PROM and 26 control cases, which delivered at term or preterm without PROM. The preterm PROM cases represented both patients who labored and those who did not. Membrane samples at the rupture site and a remote site (approximately > 5 cm) were analyzed for MMP-9 protein and enzymatic activity by Western blot and gelatin zymography, respectively. RESULTS: MMP-9 levels in fetal membranes were similar at both the rupture and the remote sites. The highest levels of total MMP-9 protein were found in preterm PROM patients with labor (p < 0.05) and were increased four-fold over protein levels in non-laboring preterm PROM patients delivered by Cesarean section (p < 0.001). In preterm PROM patients without labor, levels of MMP-9 protein were similar to those of non-laboring patients at term and preterm. Zymography correlated with protein results in all membranes. CONCLUSIONS: Preterm PROM without labor is not associated with increased membrane levels of MMP-9 protein, suggesting that its local elevation does not play a role in early membrane rupture.