Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage.

PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

Ruptura prematura de membranas ovulares / Premature rupture of ovular membranes

La ruptura prematura de las membranas ovulares se define como la pérdida de la integridad del amnios y corion antes del inicio del trabajo de parto, afecta el 3 % de los embarazos, causa un tercio de los partos pretérminos, los cuales ocupan el 10,49 % de los nacimientos y es el origen de altos índices de morbimortalidad perinatal. En la actualidad, el manejo de esta patología se orienta principalmente en evitar los factores de riesgo, hacer un diagnóstico adecuado, determinar la edad gestacional en que ocurre, realizar el monitoreo exhaustivo del bienestar materno-fetal y en decidir el momento idóneo de finalización de la gestación para minimizar sus complicaciones. Debido a la compleja y lábil estructura histológica de las membranas ovulares, se ha dejado a un lado el tratamiento directo de la entidad el cual sería sellar o reparar el defecto en sí. En los últimos años, numerosos estudios y protocolos clínicos de prestigiosos centros asistenciales han servido como guía para el manejo de esta entidad, pero en muy pocos se observa una terapia destinada a la reparación de dichas membranas o en sellar tal defecto. Las evidencias científicas demuestran que la regeneración y reparación de las membranas es lenta y compleja y los tratamientos propuestos para reparar o sellar su defecto no han gozado de la aceptación científica para su aprobación, sin embargo, el uso del parche hemático transvaginal endocervical autólogo luce como una alternativa terapéutica prometedora(AU)

The premature rupture of the ovular membranes is defined as the loss of the integrity of the amnion and chorion before the on set of labor, affects 3% of pregnancies, causes athird of preterm births which occupy 10,49% of births and is the origin of high rates of perinatal morbidity and mortality. At present, the management of this pathology is mainly oriented towards avoiding risk factors, making an adequate diagnosis, determining the gestational age in which it occurs, carrying out exhaustive monitoring of maternal-fetal well-being and deciding the ideal moment to end the treatment. Pregnancy to minimizeits complications. Due to the complex and labile histological structure of the ovular membranes, the direct treatment of the entity has been set a side, which would be to seal or repairthe defect it self. In recent years, numerous studies and clinicalprotocols from prestigious health care centers have served as aguide for the management of this entity, but very few have observed a therapy aimed at repairing said membranes or sealing such a defect. Scientific evidence shows that the regeneration and repair of the membranes is slow and complex and the treatment sproposed to repair or seal their defect have not enjoyed scientific acceptance for their approval, how ever, the use of the autologous endocervical transvaginal blood patch looks like a promising therapeutic alternative(AU)

Circulating Extracellular Vesicles microRNAs Are Altered in Women Undergoing Preterm Birth.

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women-15 preterm and 16 term-were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis.

Association of maternal, fetal and labor variables with a low Apgar score in the fifth minute in term pregnancy: a case-control study.

PURPOSE: To search for maternal, labor-related and fetal variables associated with low Apgar in the fifth minute in term pregnancy. METHODS: A retrospective case-control study with term births was conducted in a public teaching hospital from 2013 to 2020. Cases were term births with Apgar score less than 7 in the fifth minute, and controls, the next one or two births following a case, with Apgar of 7 or more. Non-cephalic presentations, multiples and malformations were excluded. We accessed 100 cases and 190 controls. We considered significant values of p < 0.05. RESULTS: Were accessed 27 variables which could be risk factors, from which 12 were associated with the outcome. We found a protective effect of prelabor cesarean for the outcome, odds ratio (OR) 0.38, p = 0.013. Consequently, we conducted two sets of analyses: in the whole group and in the group of laboring women. The values of OR were in general greater in the group of laboring women, compared with the whole group. We conducted multivariate analysis within the group of women in labor. The variables which fitted best in the model were nulliparity, male sex of the fetus, less than six prenatal visits and abnormal cardiotocography; all remained significant. An association of rupture of membranes more than 360 min with the outcome, even after controlling fpr duration of labor, was found; adjusted OR 2.45, p = 0.023. CONCLUSION: Twelve variables were associated with the outcome. Prelabor cesarean had a protective effect. The time of ruptured membranes was associated with low Apgar.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage

ABSTRACT Purpose: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. Methods: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. Results: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). Discussion: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.

Complicaciones materno-fetales en embarazadas añosas. Centro de salud san jacinto de buena fe, 2020 / Maternal-fetal complications in elderly pregnant women. San Jacinto de Buena Fe Health Center, 2020

El embarazo añoso representa una problemática de salud pública debido a sus repercusiones en el binomio madre-hijo. Objetivo. Determinar las complicaciones materno-fetales en embarazadas añosas atendidas en el Centro de Salud Tipo C San Jacinto de Buena Fe durante el periodo enero y diciembre del 2020. Materiales y métodos. El diseño de investigación observacional, cuantitativo, retrospectivo, descriptivo de corte transversal con una muestra de 80 gestantes mayores de 35 años, como instrumento se empleó un formulario de recolección de datos que constó de 12 ítems validados por un juicio de expertos. Resultados. Las caracteristicas sociodemográficas de interés en las pacientes del estudio fueron: grupo etario de 35-37 años con el 67,2 %, unión libre con 52,5 %, grado de instrucción primario con el 46,3 % y procedencia rural en el 95 %; entre las complicaciones maternas: ruptura prematura de membranas con el 25 %, trastornos hipertensivos en el 16,2 % y aborto espontáneo con el 13,7 %; las complicaciones fetales: prematuridad con el 17,5 %, bajo peso al nacer con el 17,5 % y síndrome de dificultad respiratoria con el 11,2%. Conclusión. Fue posible establecer las características sociodemográficas de interés en la muestra de estudio, identificar algunos factores de riesgo de complicaciones y determinar las complicaciones que comprometen a la madre y al hijo/a en embarazos de edad avanzada.

Elderly pregnancy represents a public health problem due to its repercussions on the mother-child binomial. Objective. To determine the maternal-fetal complications in elderly pregnant women treated at the San Jacinto de Buena Fe Type C Health Center during the period January and December 2020. Materials and methods. The observational, quantitative, retrospective, descriptive cross-sectional research design with a sample of 80 pregnant women over 35 years of age, as an instrument a data collection form that consisted of 12 items validated by an expert judgment was used. Results. The sociodemographic characteristics of interest in the study patients were age group 35-37 years with 67.2%, free union with 52.5%, grade of primary education with 46.3% and rural origin in 95 %; among maternal complications: premature rupture of membranes with 25%, hypertensive disorders in 16.2% and spontaneous abortion with 13.7%; fetal complications: prematurity with 17.5%, low birth weight with 17.5% and respiratory distress syndrome with 11.2%. Conclusion. It was possible to establish the sociodemographic characteristics of interest in the study sample, identify some risk factors for complications, and determine the complications that affect the mother and the child in older pregnancies(AU)

El prematuro tardío, ¿qué sabemos desde el punto de vista perinatal? / The late premature, what do we know from the perinatal point of view?

Resumen El parto prematuro es la principal causa de morbimortalidad neonatal en Chile. Los prematuros tardíos, definidos como nacimientos entre 34 semanas con 0 días (34+0) y 36 semanas con 6 días (36+6) de gestación, representan el 70-80% de los prematuros y se asocian a baja morbilidad y excepcional mortalidad si se comparan con partos bajo 34 semanas, pero significativamente mayor al compararlos con partos de término. Los prematuros tardíos son el resultado de diversas condiciones obstétricas, tales como síndromes hipertensivos del embarazo, rotura prematura de membranas, colestasia intrahepática del embarazo y comorbilidad médica. El propósito de esta revisión es actualizar la información asociada a los prematuros tardíos y dar una visión de las tendencias en el uso de corticoides y el manejo expectante de la rotura prematura de membranas con el objetivo de disminuir las complicaciones en este grupo de prematuros.

Abstract Preterm delivery is the most important cause of neonatal morbidity and mortality in Chile. Late preterm, defined as deliveries between 34 +0 and 36+6-weeks accounts for 70-80% of preterm and is associated with non-severe morbidity and extremely low mortality when compared with deliveries below 34 weeks but significantly high when compared with full term babies. Late preterm deliveries are a result of several obstetric conditions, such a hypertensive disorder, premature rupture of membranes, intrahepatic cholestasis, and maternal medical comorbidities. The purpose of this review is to update the information associated with the risks of late preterm and to guide in the new trends in the application of steroid and expectant management for premature rupture of membranes in order to reduce the frequency of late preterm.

COVID 19 and high pregnancy and perinatal complications in Panama.

OBJECTIVES: To report the maternal and neonatal results of patients infected with COVID-19 in Panama. METHODS: The study is based on the analysis of pregnant women with COVID-19, in five hospitals in the Republic of Panama. The inclusion criteria were: patients with or without symptoms, positive RT-PCR for SARS-CoV-2 in the period from March 23 to 6 months after, whose births were attended in one of those five hospitals and who signed the consent. Data were obtained at the time of diagnosis of the infection and at the time of termination of pregnancy for the mother and newborn. RESULTS: Two hundred and fifty-three patients met the inclusion criteria. Most were diagnosed in the third trimester (89.3%). 10.3% of the patients presented in a severe form of COVID-19. The most frequent complication was pre-eclampsia and if we add gestational hypertension they represent 21.2%; most of the patients terminated the pregnancy by cesarean section (58%). 26.9% (95% CI 21.3-32.9%) of the births were premature, and perinatal mortality was 5.4% (95% CI 3.0-9.0%). There was a need for mechanical ventilation in 5.9% (95% CI 3.6-9.6%) of the cohort and there were four maternal deaths (1.6% - 95% CI 0.6-4.0%). CONCLUSIONS: This study of pregnant women infected with COVID-19 and diagnosed with RT-PCR shows serious maternal complications such as high admission to the ICU, need for mechanical ventilation and one death in every 64 infected. Frequent obstetric complications such as hypertension, premature rupture of membranes, high rate of prematurity, and perinatal lethality were also seen.

Maternal and perinatal outcomes in midtrimester rupture of membranes.

OBJECTIVE: The aim of this study was to assess neonatal and maternal adverse outcomes following expectant management of preterm prelabor rupture of membranes (PPROM) between 18 and 26 weeks and to identify maternal morbidity and prognostic factors for neonatal outcomes. METHODS: Data were collected from all pregnant women who presented PPROM between 18+0 and 26+0 weeks admitted into two tertiary centers in Brazil from 2005 to 2016. The neonatal adverse outcomes (mortality or the development of a severe morbidity) and maternal adverse outcomes were analyzed and compared among four groups (180/7 to 200/7 weeks, 20+1 to 220/7 weeks, 22+1 to 240/7 weeks and 24+1 to 260/7 weeks). A multiple logistic regression was performed for each predictor of neonatal adverse outcomes, and the area under the receiver operating characteristics curves for birth weight and gestational age at birth were calculated. RESULTS: Of the 101 women with PPROM during the study period, 97 fulfilled the eligible criteria. Among these patients, 30 (30.9%) had a miscarriage or stillbirth. Overall there were 67/97 (69.1%) livebirths, 45/97 newborns survived to discharge (46.3%), and 53/97 (54.6%) experienced severe neonatal adverse outcome. The median latency period was seven days, with 36 (37.1%) patients ending the pregnancy in 2-14 days. Among 29 patients with PPROM at 24+1 to 260/7 weeks, only 13 (44.8%) delivered between 2 and 14 days. Multivariate analysis has demonstrated that the independent predictor for adverse neonatal outcome was birthweight. The maternal morbidity was high; however, the expectant management did not increase the rate of severe maternal morbidity. CONCLUSIONS: PPROM between 18+0 and 26+0 weeks has high morbidity and mortality, and the only significant independent predictor of severe adverse neonatal outcomes is birthweight. Maternal morbidity is high, however, the expectant management is not increased by expectant management.

Beneficios de los antibióticos en la rotura prematura de membranas de pretérmino y factores que intervienen en la eficacia del tratamiento: revisión narrativa / Benefits of antibiotics in preterm premature rupture of membranes and factors involved in the efficacy of the treatment: narrative review

Resumen El parto prematuro es la principal causa de morbilidad y de mortalidad perinatal, y hasta un tercio de los casos presentan rotura prematura de membranas. La infección intrauterina que asciende desde la vagina es su principal causa en un hospital público de Chile. Esta revisión narrativa mediante búsqueda en PubMed, Cochrane, Embase, Scielo, Science Direct y Wiley Online Library incluye estudios publicados sobre los diferentes factores infecciosos que intervienen en el resultado adverso perinatal y la eficacia de los antibióticos en la rotura prematura de membranas de pretérmino. Además, contiene recomendaciones de sociedades científicas sobre el uso de antibióticos en estos casos. Los ensayos concluyen que los antimicrobianos prolongan el embarazo, disminuyen la corioamnionitis clínica y reducen variadas morbilidades neonatales, pero no reducen la mortalidad perinatal ni las secuelas tardías en la infancia. Los resultados adversos obstétricos, especialmente los neonatales, y las secuelas dependen de la existencia de invasión microbiana de la cavidad amniótica o de infección cérvico-vaginal, de la virulencia de los microorganismos aislados, del compromiso inflamatorio/infeccioso de la placenta (corioamnionitis histológica, funisitis) y de la respuesta inflamatoria fetal. Para mejorar los resultados adversos obstétricos neonatales en la rotura prematura de membranas de pretérmino, los esquemas de antibióticos deben ser eficaces, cubriendo el amplio espectro microbiológico existente y actuando sobre los factores infecciosos implicados en la gravedad de la infección. Además, deben administrarse de manera intensiva y prolongada hasta el parto.

Abstract Preterm birth is the leading cause of perinatal morbidity and mortality, and up to a third of them have premature rupture of membranes. Intrauterine infection that rises from the vagina is its main cause in a public hospital in Chile. This narrative review by searching PubMed, Cochrane, Embase, Scielo, Science Direct and Wiley Online Library includes published studies of the different infectious factors involved in perinatal adverse outcome and of the efficacy of antibiotics in preterm premature rupture of membranes. It also contains recommendations from scientific societies on the use of antibiotics in these cases. These trials conclude that antimicrobials prolong pregnancy, decrease clinical chorioamnionitis, and reduce various neonatal morbidities, but do not reduce perinatal mortality or infant sequelae. Obstetric and especially neonatal adverse outcomes in these patients depend on the existence of microbial invasion of the amniotic cavity and/or cervicovaginal infection, of the virulence of the isolated microorganisms, of inflammatory/infectious involvement of the placenta (histological chorioamnionitis, funisitis) and fetal inflammatory response. To improve adverse neonatal obstetric outcomes in preterm premature rupture of membranes, antibiotic regimens must be effective, covering the wide existing microbiological spectrum and acting on infectious factors responsible for the severity of the infection. In addition, they must be administered aggressively and for a long time until delivery.

Induction within or after 12 hours of ≥36 weeks' prelabor rupture of membranes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the incidence of chorioamnionitis in women with singleton gestations with ≥36 weeks' prelabor rupture of membranes induced with oxytocin within or after 12 hours of prelabor rupture of membranes. DATA SOURCES: The search was conducted using MEDLINE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID, and Cochrane Library as electronic databases from their inception to May 2020. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials of women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks comparing induction of labor with oxytocin either ≤12 hours after prelabor rupture of membranes or >12 hours after prelabor rupture of membranes (expectant management group). STUDY APPRAISAL AND SYNTHESIS METHODS: The risk of bias in each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. The primary outcome was the incidence of chorioamnionitis. RESULTS: After exclusions, 9 randomized controlled trials including 3759 women were analyzed. Women with singleton cephalic gestations and prelabor rupture of membranes at ≥36 weeks who have induction of labor ≤12 hours after prelabor rupture of membranes have shorter time between prelabor rupture of membranes and delivery (-12.68 hours; 95% confidence interval, -16.15 to -9.21) and higher chance of delivering within 24 hours of prelabor rupture of membranes (91% vs 46%; relative risk, 1.93; 95% confidence interval, 1.59-2.35). Cesarean and operative vaginal deliveries were not significantly different between the groups. Induction of labor ≤12 hours after prelabor rupture of membranes was also associated with significantly fewer incidences of chorioamnionitis (5.3% vs 9.9%; relative risk, 0.62; 95% confidence interval, 0.40-0.97), endometritis (2.4% vs 4.2%; relative risk, 0.59; 95% confidence interval, 0.40-0.87), neonatal sepsis (6.1% vs 11.8%; relative risk, 0.46; 95% confidence interval, 0.27-0.79), and admission to neonatal intensive care unit (6.4% vs 12.0%; relative risk, 0.54; 95% confidence interval, 0.43-0.69) compared with women managed expectantly, usually at >24 hours. The subgroup analysis of 3323 women with induction of labor at ≤6 hours showed similar results, including similar significant reductions in chorioamnionitis, endometritis, neonatal sepsis, and admission to neonatal intensive care unit. CONCLUSION: Women with symptoms of prelabor rupture of membranes at ≥36 weeks should be evaluated promptly, and if prelabor rupture of membranes is confirmed, they should have induction of labor within 12 hours and perhaps even within 6 hours since the first symptom of prelabor rupture of membranes. This management is associated with significantly less morbidity, especially in terms of infections, for both the mother and the baby, with no evidence of any harm.

Pregnancy latency after preterm premature rupture of membranes: oral versus intravenous antibiotics.

BACKGROUND: Following the destruction of pharmaceutical production facilities in Puerto Rico by Hurricane Maria in September 2017, a shortage of small-volume bags of sterile intravenous fluid for infusion led to a decreased ability to administer intravenous azithromycin and ampicillin efficiently for use in the treatment of patients with preterm premature rupture of membranes. OBJECTIVE: This study aimed to assess pregnancy latency after preterm premature rupture of membranes following treatment with oral-only antibiotics compared with treatment with intravenous antibiotics followed by oral antibiotics. STUDY DESIGN: This is a retrospective historic control study comparing women with preterm premature rupture of membranes who were initiated on a 7-day oral-only regimen of azithromycin and amoxicillin (modified regimen) during a 12-month period beginning December 2017 (during which time there was a shortage of small-volume bags of intravenous fluid) to women with preterm premature rupture of membranes who were initiated on a 2-day regimen of intravenous ampicillin and azithromycin followed by 5 days of oral amoxicillin and azithromycin (standard regimen) from December 2016 to December 2018. Women were included in the study if they were diagnosed with preterm premature rupture of membranes at <34 weeks' gestation and were started on latency antibiotics, and women were excluded from the study if they had a contraindication to expectant management, a cerclage, or suspected fetal anomalies. The primary outcome was pregnancy latency, defined as time from the first dose of antibiotics to delivery. RESULTS: The 37 women who received the modified regimen and the 79 women who received the standard regimen had similar baseline characteristics. Mean (standard deviation) gestational age at time of preterm premature rupture of membranes was similar between the modified (30.5 weeks' gestation [±3.1]) and standard regimen groups (30.2 weeks' gestation [±3.2]), and the rate of group B streptococcus rectovaginal colonization was similar for both groups (27% vs 24%; P=.95). Pregnancy latency did not differ in the modified vs standard regimen (mean difference, -0.15 days; 95% confidence interval, -4.87 to 4.58) There was no statistically significant difference in the relative risk of composite maternal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.53) or composite neonatal infection (relative risk, 0.43; 95% confidence interval, 0.05-3.52). CONCLUSION: Although limited by small sample size, our study suggested that adoption of an oral-only antibiotic regimen for pregnancy latency following preterm premature rupture of membranes is worthy of further study.

Congenital Heart Defects and the Risk of Spontaneous Preterm Birth.

OBJECTIVES: To estimate the association between major types of congenital heart defects (CHD) and spontaneous preterm birth, and to assess the potential underlying mechanisms. STUDY DESIGN: This nationwide, registry-based study included a cohort of all singleton pregnancies in Denmark from 1997 to 2013. The association between CHD and spontaneous preterm birth was estimated by multivariable Cox regression, adjusted for potential confounders. The following potential mechanisms were examined: maternal genetics (sibling analyses), polyhydramnios, preterm prelabor rupture of membranes, preeclampsia, and indicators of fetal and placental growth. RESULTS: The study included 1 040 474 births. Compared with the general population, CHD was associated with an increased risk of spontaneous preterm birth, adjusted hazard ratio 2.1 (95% CI, 1.9-2.4). Several subtypes were associated with increased risks, including pulmonary stenosis combined with a septal defect, 5.2 (95% CI, 3.7-7.5); pulmonary stenosis or atresia, 3.1 (95% CI, 2.4-4.1); tetralogy of Fallot 2.5 (95% CI, 1.6-3.8); coarctation or interrupted aortic arch 2.2 (95% CI, 1.5-3.2); and hypoplastic left heart syndrome, 2.0 (95% CI, 1.0-4.1). Overall, preterm prelabor rupture of membranes mediated more than one-half of the association. Maternal genetics, polyhydramnios, or indicators of fetal or placental growth did not explain the reported associations. CONCLUSIONS: CHD, especially right ventricular outflow tract obstructions, were associated with an increased risk of spontaneous preterm birth. The risk was carried by the CHD and not by maternal genetics. Moreover, preterm prelabor rupture of membranes was identified as a potential underlying mechanism.

Evidence-based labor management: first stage of labor (part 3).

There are several interventions during the first stage of labor that have been studied. Vaginal disinfection with chlorhexidine cannot be recommended. Intrapartum antibiotic prophylaxis is recommended for group B streptococcus-positive women. Antibiotic therapy can be considered in women with term prelabor rupture of membranes whose latency is expected to be >12 hours. Aromatherapy with essential oils through inhalation or back massage can be considered. Immersion in water can be considered. Oral restriction of fluid or solid food is not recommended. In the setting of oral restriction, intravenous fluid containing dextrose at a rate of 250 mL/h is recommended. Upright positions and ambulation are recommended in women without regional anesthesia, and women with regional anesthesia can adopt whatever position they find most comfortable and choose to ambulate or not ambulate. Continuous bladder catheterization cannot be recommended. There is no recommended frequency of cervical examinations or sweeping of membranes. The use of a partogram cannot be recommended as a routine intervention. Routine use of the peanut ball cannot be recommended. Antispasmodic agents cannot be recommended. Routine amniotomy alone in normally progressing spontaneous first stage of labor cannot be recommended. Oxytocin augmentation is recommended to shorten the time to delivery for women making slow progress in spontaneous labor, and higher doses of oxytocin can be considered. Early intervention with oxytocin and amniotomy for the prevention and treatment of dysfunctional or slow labor is recommended. Routine use of intrauterine pressure catheter and ultrasound cannot be recommended. Cesarean delivery for arrest should not be performed unless labor has arrested for a minimum of 4 hours with adequate uterine activity or 6 hours with inadequate uterine activity in a woman with rupture of membranes, adequate oxytocin, and ≥6 cm cervical dilation.

Active versus expectant management for preterm premature rupture of membranes at 34-36 weeks of gestation and the associated adverse perinatal outcomes / Manejo ativo versus expectante para ruptura prematura de membranas entre 34 e 36 semanas de gestação e os resultados perinatais adversos associados

Abstract Objective: To compare the type of management (active versus expectant) for preterm premature rupture of membranes (PPROM) between 34 and 36 + 6 weeks of gestation and the associated adverse perinatal outcomes in 2 tertiary hospitals in the southeast of Brazil. Methods: In the present retrospective cohort study, data were obtained by reviewing the medical records of patients admitted to two tertiary centers with different protocols for PPROM management. The participants were divided into two groups based on PPROM management: group I (active) and group II (expectant). For statistical analysis, the Student t-test, the chi-squared test, and binary logistic regression were used. Results: Of the 118 participants included, 78 underwent active (group I) and 40 expectant management (group II). Compared with group II, group I had significantly lower mean amniotic fluid index (5.5 versus 11.3 cm, p = 0.002), polymerase chain reaction at admission (1.5 versus 5.2 mg/dl, p = 0.002), time of prophylactic antibiotics (5.4 versus 18.4 hours, p < 0.001), latency time (20.9 versus 33.6 hours, p = 0.001), and gestational age at delivery (36.5 versus 37.2 weeks, p = 0.025). There were no significant associations between the groups and the presence of adverse perinatal outcomes. Gestational age at diagnosis was the only significant predictor of adverse composite outcome (x2 [1] = 3.1, p = 0.0001, R2 Nagelkerke = 0.138). Conclusion: There was no association between active versus expectant management in pregnant women with PPROM between 34 and 36 + 6 weeks of gestation and adverse perinatal outcomes.

Resumo Objetivo: Comparar o tipo de manejo (ativo versus expectante) para ruptura prematura de membranas (PPROM, na sigla em inglês) entre 34 e 36 semanas e 6 dias de gestação e os resultados perinatais adversos relacionados, em 2 hospitais terciários do sudeste brasileiro. Métodos: No presente estudo de coorte retrospectivo, os dados foram obtidos através da revisão dos prontuários de gestantes internadas em dois centros terciários com protocolos diferentes para o seguimento da PPROM. As gestantes foram divididas em dois grupos com base no manejo da PPROM: grupo I (ativo) e grupo II (expectante). Para análise estatística, foram utilizados o teste t de Student, qui-quadrado e regressão logística binária. Resultados: Das 118 gestantes incluídas, 78 foram submetidas a tratamento ativo (grupo I) e 40 a seguimento expectante (grupo II). Comparado ao grupo II, o grupo I apresentou índice de líquido amniótico médio significativamente menor (5,5 versus 11,3 cm, p = 0,002), reação em cadeia da polimerase na admissão (1,5 versus 5,2 mg/dl, p = 0,002), tempo de antibióticos profiláticos (5,4 versus 18,4 horas, p < 0,001), tempo de latência (20,9 versus 33,6 horas, p = 0,001) e idade gestacional no parto (36,5 versus 37,2 semanas, p = 0,025). Não houve associações significativas entre os grupos e a presença de resultados perinatais adversos. A idade gestacional no diagnóstico foi o único preditor significativo de desfecho composto adverso (x2 [1] = 3,1, p = 0,0001, R2 Nagelkerke = 0,138). Conclusão: Não houve associação entre manejo ativo e expectante em gestantes com PPROM entre 34 e 36 semanas e 6 dias de gestação e resultados perinatais adversos.

Comparison of two identification and susceptibility test kits for Ureaplasma spp and Mycoplasma hominis in amniotic fluid of patients at high risk for intra-amniotic infection.

Objective: Ureaplasma urealyticum and Mycoplasma hominis are the most common microorganisms found in the amniotic fluid of patients at risk for preterm delivery. However, culture techniques for genital mycoplasms require special conditions, are barely considered as part of the evaluation of suspected intra-amniotic infection (IAI) and the results are available within 2 and 7 days. The objectives of this study are to validate the use of two commercially available kits (Mycoplasma IES y MYCOFAST® RevolutioN) for the identification of Ureaplasma spp. and Mycoplasma hominis in amniotic fluid, to compare the results of these kits with those obtained by culture and real-time polymerase chain reaction (qPCR) and to report the antibiotic sensitivity profile of the genital mycoplasms identified.Methods: This is a prospective cohort study including women with singleton and twin gestations between 16 and 36 weeks. Patients were admitted to perform an amniocentesis due to pregnancy complications considered at high risk for IAI (e.g. preterm labor with intact membranes, preterm prelabour rupture of membranes, short cervix, etc.), treatment of polyhydramnios, and for the assessment of fetal death and fever without a focus.Results: Overall, 93 patients underwent amniocentesis and 63 had results available for all tests. The prevalence of a positive culture was 6% (4/63). There were four cases of Ureaplasma spp. and none of Mycoplasma hominis. The qPCR identified one case as Ureaplasma spp., one case as Ureaplasma parvum and two cases as Ureaplasma urealyticum. For all tests, the diagnostic performance was as follows: sensitivity 100% [95% CI (39.8-100%)], specificity 100% [95% CI (93.9-100%)], positive predictive value 100% [95% CI (39.8-100%)] and negative predictive value 100% [95% CI (93.9-100%)]. In this cohort, Ureaplasma spp. showed low resistance to erythromycin, but a high resistance to clindamycin and clarithromycin that may change according to the antibiotic concentration.Conclusions: To our knowledge, this is the first study that validates the use of the Mycoplasma IES and MYCOFAST® RevolutioN kits for the identification of genital mycoplasmas in amniotic fluid. The results of these kits are mostly available within 24 hours, have an excellent correlation with those from broth cultures and qPCR and characterize the antibiotic sensitivity profile of the genital mycoplasms identified, providing an opportunity for specific treatment in cases of IAI. Further validation studies in other populations are needed.

Comparative analysis of Insulin-like growth factor binding protein-1, placental alpha-microglobulin-1, phenol and pH for the diagnosis of preterm premature rupture of membranes between 20 and 36 weeks.

AIM: Preterm premature rupture of membranes (PPROM) is responsible for approximately one-third of premature births worldwide, and although the diagnosis is often straightforward, this condition can still present difficulties. The purpose of this research was to compare the accuracy of several PPROM diagnostic tests. METHODS: A total of 94 pregnant women with clinical suspicion of PPROM who were between 20 and 36 weeks of pregnancy were examined by vaginal speculum, and tests were performed for phenol, pH, insulin-like growth factor binding protein-1 (IGFBP-1) and placental alpha-microglobulin-1 (PAMG-1). All patients were followed up until the diagnosis was fully defined, and a diagnosis of PROM was confirmed by a definitive evolution of the clinical symptoms (visualization of vaginal amniotic fluid or persistence of oligohydramnios). RESULTS: After excluding the cases that could not be definitively diagnosed, a good diagnostic performance of the immunochromatographic tests was observed that was superior to that of the clinical tests. Similar accuracies were observed for IGFBP-1 (98.7%) and PAMG-1 (93.9%). However, while the IGFBP-1 test differed from a vaginal pH ≥7 (88.9%) and the phenol test (85.7%), this did not occur for the PAMG-1 test. The performance of the tests was modified only by the presence of bleeding (with lower specificity rates for pH and phenol), without interference of gestational age or maternal morbidities. CONCLUSION: Immunochromatographic tests are good tools but should be used sparingly in resource-poor settings because they are expensive, and there is no significant difference between PAMG-1 and traditional tests.

Azithromycin vs erythromycin for the management of preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes complicates 2-3% of pregnancies. Many institutions have advocated for the use of azithromycin instead of erythromycin. This is secondary to national shortages of erythromycin, ease of administration, better side effect profile, and decreased cost of azithromycin as compared with erythromycin. OBJECTIVE: The objective of the study was to evaluate whether there are differences in the latency from preterm premature rupture of membranes to delivery in patients treated with different dosing regimens of azithromycin vs erythromycin. STUDY DESIGN: This is a multicenter, retrospective cohort of women with singleton pregnancies with confirmed rupture of membranes between 230 and 336 weeks from January 2010 to June 2015. Patients were excluded if there was a contraindication to expectant management of preterm premature rupture of membranes. Patients received 1 of 4 antibiotic regimens: (1) azithromycin 1000 mg per os once (azithromycin 1 day group); (2) azithromycin 500 mg per os once, followed by azithromycin 250 mg per os daily for 4 days (azithromycin 5 day group); (3) azithromycin 500 mg intravenously for 2 days, followed by azithromycin 500 mg per os daily for 5 days (azithromycin 7 day group); or (4) erythromycin intravenously for 2 days followed by erythromycin per os for 5 days (erythromycin group). The choice of macrolide was based on institutional policy and/or availability of antibiotics at the time of admission. In addition, all patients received ampicillin intravenously for 2 days followed by amoxicillin per os for 5 days. Primary outcome was latency from diagnosis of rupture of membranes to delivery. Secondary outcomes included clinical and histopathological chorioamnionitis and neonatal outcomes. RESULTS: Four hundred fifty-three patients who met inclusion criteria were identified. Seventy-eight patients received azithromycin for 1 day, 191 patients received azithromycin for 5 days, 52 patients received azithromycin for 7 days, and 132 patients received erythromycin. Women who received the 5 day regimen were younger and less likely to be non-African American, have hypertension, have sexually transmitted infection, or experienced substance abuse. There was no statistical difference in median latency time of azithromycin 1 day (4.9 days, 95% confidence interval, 3.3-6.4), azithromycin 5 days (5.0, 95% confidence interval, 3.9-6.1), or azithromycin 7 days (4.9 days, 95% confidence interval, 2.8-7.0) when compared with erythromycin (5.1 days, 95% confidence interval, 3.9-6.4) after adjusting for demographic variables (P = .99). Clinical chorioamnionitis was not different between groups in the adjusted model. Respiratory distress syndrome was increased in the azithromycin 5 day group vs azithromycin 1 day vs erythromycin (44% vs. 29% and 29%, P = .005, respectively). CONCLUSION: There was no difference in latency to delivery, incidence of chorioamnionitis, or neonatal outcomes when comparing different dosing regimens of the azithromycin with erythromycin, with the exception of respiratory distress syndrome being more common in the 5 day azithromycin group. Azithromycin could be considered as an alternative to erythromycin in the expectant management of preterm premature rupture of membranes if erythromycin is unavailable or contraindicated. There appears to be no additional benefit to an extended course of azithromycin beyond the single-day dosing, but final recommendations on dosing strategies should rely on clinical trials.

North American Fetal Therapy Network: Timing of and indications for delivery following laser ablation for twin-twin transfusion syndrome.

Background: Despite improvements in fetal survival for pregnancies affected by twin-twin transfusion syndrome since the introduction of laser photocoagulation, prematurity remains a major source of neonatal morbidity and mortality. Objective: To investigate the indications and factors influencing the timing of delivery following laser treatment, we collected delivery information regarding twin-twin transfusion syndrome cases in a large multicenter cohort. Study Design: Eleven North American Fetal Therapy Network (NAFTNet) centers conducted a retrospective review of twin-twin transfusion syndrome patients who underwent laser photocoagulation. Clinical, demographic and ultrasound variables including twin-twin transfusion syndrome stage, and gestational age at treatment and delivery were recorded. Primary and secondary maternal and fetal indications for delivery were identified. Univariate analysis was used to select candidate variables with significant correlation with latency and GA at delivery. Multivariable Cox regression with competing risk analysis was utilized to determine the independent associations. Results: A total of 847 pregnancies were analyzed. After laser, the average latency to delivery was 10.11 ± 4.8 weeks and the mean gestational age at delivery was 30.7 ± 4.5 weeks. Primary maternal indications for delivery comprised 79% of cases. The leading indications included spontaneous labor (46.8%), premature rupture of membranes (17.1%), and placental abruption (8.4%). Primary fetal indications accounted for 21% of cases and the most frequent indications included donor non-reassuring status (20.5%), abnormal donor Dopplers (15.1%), and donor growth restriction (14.5%). The most common secondary indications for delivery were premature rupture of membranes, spontaneous labor and donor growth restriction. Multivariate modeling found gestational age at diagnosis, stage, history of prior amnioreduction, cerclage, interwin membrane disruption, procedure complications and chorioamniotic membrane separation as predictors for both gestational age at delivery and latency. Conclusion: Premature delivery after laser therapy for twin-twin transfusion syndrome is primarily due to spontaneous labor, preterm premature rupture of membranes and non-reassuring status of the donor fetus. Placental abruption was found to be a frequent complication resulting in early delivery. Future research should be directed toward the goal of prolonging gestation after laser photocoagulation to further reduce morbidity and mortality associated with twin-twin transfusion syndrome.

Preterm premature rupture of membranes. / Ruptura prematura de membranas en nacimientos de pretérmino.

Preterm premature rupture of membranes occurs in around 3% of pregnancies, and several aspects related to its management are still controversial. The objective of this update is to provide a detailed review of strategies aimed at reducing morbidity and mortality associated with this maternal condition. We will discuss the available evidence regarding the maternal use of antibiotics, the use of corticosteroids according to gestational age, the use of magnesium sulphate for fetal neuroprotection, the use of tocolytic agents, and the best moment for and route of delivery. This review also covers the effects of prolonged preterm premature rupture of membranes, infant morbidity and mortality in the short and long term, the harmful effects of antibiotics after delivery, including the effects on neurodevelopment and the presence of longterm chronic diseases.

La ruptura prematura de membranas de pretérmino ocurre en, aproximadamente, el 3% de los embarazos y numerosos aspectos vinculados a su manejo continúan siendo controversiales. El objetivo de esta actualización es revisar en forma detallada las estrategias destinadas a disminuir la morbilidad y mortalidad asociadas a esta situación clínica en las madres. Se discutirá la evidencia disponible acerca del uso en las madres de antibióticos, corticoides a distintas edades gestacionales, sulfato de magnesio como neuroprotector fetal, tocolíticos y el momento óptimo y la vía de finalización del embarazo. Asimismo, se incluyen los efectos de la ruptura prolongada de membranas en prematuros, la mortalidad y morbilidad de los recién nacidos en el corto y largo plazo, los perjuicios de la administración de antibióticos luego del nacimiento con las secuelas en el neurodesarrollo y la presencia de enfermedades crónicas a largo plazo.