RESUMEN
This is a protocol for PPROM-AZM Study, phase II, nonblinded, randomized controlled trial. Bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks (BPD36) is often observed in infants with preterm premature rupture of the membranes (pPROM). A regimen of ampicillin (ABPC) intravenous infusion for 2 days and subsequent amoxicillin (AMPC) oral administration for 5 days plus erythromycin (EM) intravenous infusion for 2 days followed by EM oral administration for 5 days is standard treatment for pPROM. However, the effect on the prevention of moderate/severe BPD36 using the standard treatment has not been confirmed. Recently, it is reported that ampicillin/sulbactam (ABPC/SBT) plus azithromycin (AZM) was effective for the prevention of moderate/severe BPD36 in pPROM patients with amniotic infection of Ureaplasma species. Therefore, our aim is to evaluate the occurrence rate of the composite outcome of "incidence rate of either moderate/severe BPD36 or intrauterine fetal death, and infantile death at or less than 36 weeks 0 days" comparing subjects to receive ABPC/SBT for 14 days plus AZM for 14 days (intervention group) and those to receive ABPC/SBT for 14 days plus EM for 14 days (control group), in a total of 100 subjects (women with pPROM occurring at 22-27 weeks of gestation) in Japan. The recruit of subjects was started on April 2022, and collection in on-going. We also investigate the association between the detection of Ureaplasma species and occurrence of BPD36. In addition, information on any adverse events for the mother and fetus and serious adverse events for infants are collected during the observation period. We allocate patients at a rate of 1:1 considering two stratification factors: onset of pPROM (22-23 or 24-27 weeks) and presence/absence of a hospital policy for early neonatal administration of caffeine. Trial registration: The trial number in the Japan Registry of Clinical Trials is jRCTs031210631.
Asunto(s)
Ampicilina , Antibacterianos , Azitromicina , Displasia Broncopulmonar , Eritromicina , Rotura Prematura de Membranas Fetales , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Ampicilina/administración & dosificación , Ampicilina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Azitromicina/administración & dosificación , Azitromicina/uso terapéutico , Displasia Broncopulmonar/prevención & control , Displasia Broncopulmonar/tratamiento farmacológico , Quimioterapia Combinada , Eritromicina/uso terapéutico , Eritromicina/administración & dosificación , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Edad Gestacional , Japón/epidemiología , Sulbactam/administración & dosificación , Sulbactam/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase II como AsuntoRESUMEN
Spontaneous previable rupture of membranes complicates approximately 0.4-0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure-volume ratios. The supposed basis of this physical-mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical-academic and publishing outputs of the authors based on their many years' experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008-2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research-academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Fibrinógeno , Humanos , Embarazo , Femenino , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/terapia , Fibrinógeno/uso terapéutico , Corioamnionitis/tratamiento farmacológico , Antiinflamatorios/uso terapéutico , Recién Nacido , Antiinfecciosos/uso terapéutico , Factor VIIIRESUMEN
BACKGROUND: Bacterial organisms causing neonatal sepsis have developed increased resistance to commonly used antibiotics. Antimicrobial resistance is a major global health problem. The spread of Multidrug-Resistant Organisms (MDROs) is associated with higher morbidity and mortality rates. This study aimed to determine the risk factors for developing MDRO neonatal sepsis in the Neonatal Intensive Care Unit (NICU), dr. Ramelan Navy Central Hospital, in 2020-2022. METHODS: A cross-sectional study was performed on 113 eligible neonates. Patients whose blood cultures were positive for bacterial growth and diagnosed with sepsis were selected as the study sample. Univariate and multivariate analysis with multiple logistic regression were performed to find the associated risk factors for developing multidrug-resistant organism neonatal sepsis. A p-value of < 0.05 was considered significant. RESULTS: Multidrug-resistant organisms were the predominant aetiology of neonatal sepsis (91/113, 80.5%). The significant risk factors for developing MDRO neonatal sepsis were lower birth weight (OR: 1.607, 95% CI: 1.003 - 2.576, p-value: 0.049), history of premature rupture of the membrane (ProM) ≥ 18 (OR: 3.333, 95% CI: 2.047 - 5.428, p-value < 0.001), meconium-stained amniotic fluid (OR: 2.37, 95% CI: 1.512 - 3.717, p-value < 0.001), longer hospital stays (OR: 5.067, 95% CI: 2.912 - 8.815, p-value < 0.001), lower Apgar scores (OR: 2.25, 95% CI: 1.442 - 3.512, p-value < 0.001), and the use of respiratory support devices, such as invasive ventilation (OR: 2.687, 95% CI: 1.514 - 4.771, p-value < 0.001), and non-invasive ventilation (OR: 2, 95% CI: 1.097 - 3.645, p-value: 0.024). CONCLUSIONS: Our study determined various risk factors for multidrug-resistance organism neonatal sepsis and underscored the need to improve infection control practices to reduce the existing burden of drug-resistant sepsis. Low-birth-weight, a maternal history of premature rupture of the membrane lasting more than 18 hours, meconium-stained amniotic fluid, longer hospital stays, a low Apgar score, and the use of ventilators were the risk factors for developing drug-resistant neonatal sepsis.
Asunto(s)
Rotura Prematura de Membranas Fetales , Enfermedades del Recién Nacido , Sepsis Neonatal , Complicaciones del Embarazo , Sepsis , Recién Nacido , Femenino , Humanos , Sepsis Neonatal/tratamiento farmacológico , Sepsis Neonatal/epidemiología , Farmacorresistencia Bacteriana Múltiple , Centros de Atención Terciaria , Estudios Transversales , Antibacterianos/uso terapéutico , Sepsis/complicaciones , Complicaciones del Embarazo/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Factores de RiesgoRESUMEN
OBJECTIVE: To assess whether earlier administration of antibiotic prophylaxis after prelabor rupture of membranes (PROM) at term would decrease the incidence of maternal and neonatal infections. METHODS: This is a retrospective cohort study comparing women with term PROM who were initiated antibiotic prophylaxis within or after 6 h, and within or after 12 h from PROM to delivery during January 2019 to December 2021. Women with term PROM receiving cephalosporin and without contraindications to vaginal delivery or confirmed or suspected infection were included in the study. The primary outcome was puerperal infection, which refers to the reproductive tract infection occurring within 42 days of delivery. The type of pharmacoeconomic evaluation was selected based on the results of compared effectiveness between the early group and the late group. Propensity-score matching (PSM) was used to adjust confounding. Subgroup and sensitivity analyses were used to verify the robustness of results. RESULTS: We enrolled 5353 women with term PROM, including 4331 initiated with antibiotic within 6 h, 1022 after 6 h, 5077 within 12 h, and 276 after 12 h. After PSM, no significant difference was observed in the baseline characteristics of the groups. There was no statistical difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in puerperal infection (4.6% vs. 4.3%, P = 0.826; 2.9% vs. 4.6%, P = 0.471, respectively), total maternal infection, neonatal sepsis, and total neonatal infection. Cost-minimization analysis showed there was no significant difference between antibiotic use within 6 h and after 6 h, or within 12 h and after 12 h, in direct medical costs. CONCLUSION: This study showed that there was no statistical difference in the efficacy and economy of antibiotic prophylaxis used within 6-12 h after rupture of membranes versus after 6-12 h in women with term PROM.
Asunto(s)
Rotura Prematura de Membranas Fetales , Infección Puerperal , Embarazo , Recién Nacido , Femenino , Humanos , Profilaxis Antibiótica , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Estudios Retrospectivos , Antibacterianos/uso terapéuticoRESUMEN
BACKGROUND: Idiopathic bleeding in the second trimester of pregnancy complicates <1% of all pregnancies. This pregnancy complication can be caused by alterations in local hemostasis in the decidua due to infection/inflammation in the choriodecidual niche. This condition is associated with intraamniotic inflammatory complications. Antibiotic therapy effectively reduces the intensity of intraamniotic inflammation in certain pregnancy pathologies. However, whether antibiotic administration can reduce the intensity of the intraamniotic inflammatory response or eradicate microorganisms in patients with idiopathic bleeding during the second trimester of pregnancy remains unclear. OBJECTIVE: This study primarily aimed to determine whether antimicrobial agents can reduce the magnitude of intraamniotic inflammation in patients with idiopathic bleeding in the second trimester of pregnancy by assessing the concentration of interleukin-6 in the amniotic fluid before and after 7 days of antibiotic treatment. The secondary aim was to determine whether treatment with a combination of antibiotics altered the microbial load of Ureaplasma species DNA in amniotic fluid. STUDY DESIGN: This retrospective cohort study included singleton-gestation patients with idiopathic bleeding between 15+0 and 27+6 weeks who underwent transabdominal amniocentesis at the time of admission. Follow-up amniocentesis was performed in a subset of patients unless abortion or delivery occurred earlier. Concentrations of interleukin-6 were measured in the amniotic fluid samples, and the presence of microbial invasion of the amniotic cavity was assessed using culture and molecular microbiological methods. Intraamniotic inflammation was defined as an interleukin-6 concentration ≥3000 pg/mL in the amniotic fluid samples. RESULTS: A total of 36 patients with idiopathic bleeding in the second trimester of pregnancy were included. All the patients underwent initial amniocentesis. Patients with intraamniotic inflammation (n=25) were treated using a combination of antibiotics consisting of intravenous ceftriaxone, intravenous metronidazole, and peroral clarithromycin. The patients without intraamniotic inflammation (n=11) were treated expectantly. In total, 25 patients delivered 7 days after admission. All patients with intraamniotic inflammation at the initial amniocentesis who delivered after 7 days underwent follow-up amniocentesis. Treatment with antibiotics decreased the interleukin-6 concentration in the amniotic fluid at follow-up amniocentesis compared with that at the initial amniocentesis in patients with intraamniotic inflammation (median [interquartile range]: 3457 pg/mL [2493-13,203] vs 19,812 pg/mL [11,973-34,518]; P=.0001). Amniotic fluid samples with Ureaplasma species DNA had a lower microbial load at the time of follow-up amniocentesis compared with the initial amniocentesis (median [interquartile range]: 1.5×105 copies DNA/mL [1.3×105-1.7×105] vs 8.0×107 copies DNA/mL [6.7×106-1.6×108]; P=.02). CONCLUSION: Antibiotic therapy was associated with reduced intraamniotic inflammation in patients with idiopathic bleeding in the second trimester complicated by intraamniotic inflammation. Moreover, antibiotic treatment has been associated with a reduction in the microbial load of Ureaplasma species DNA in the amniotic fluid.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Embarazo , Femenino , Humanos , Segundo Trimestre del Embarazo , Corioamnionitis/microbiología , Interleucina-6 , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Inflamación/complicaciones , Amniocentesis/efectos adversos , Líquido Amniótico/microbiología , Ureaplasma , Hemorragia Uterina , ADN , Rotura Prematura de Membranas Fetales/tratamiento farmacológicoRESUMEN
BACKGROUND: Medication use in pregnancy is common; however, it is unknown if clinical practice guideline (CPG) prescribing recommendations referred to in Australia at the state, national and international level are consistent. AIMS: This systematic review aimed to: (1) identify sources of CPGs that inform prescribing during pregnancy in Australia; (2) assess CPG quality; and (3) evaluate variation within CPG recommendations for medication use in three common conditions in pregnancy: prophylactic antibiotics following premature rupture of membranes (PROM) at term, antidepressants in pregnancy and metformin in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A literature search was conducted across PubMed, Scopus and EMBASE databases. Grey literature was identified through publicly available Australian policy statements. Prescribing recommendations for prophylactic antibiotics following PROM at term, antidepressants in pregnancy and metformin in GDM, were compared at the state, national and international levels. CPG quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. RESULTS: We identified 39 CPG sources that inform prescribing during pregnancy in Australia. CPG quality varied between resources. There was minor variation in recommendations for antibiotic prophylaxis in PROM at term. Recommendations regarding metformin use in GDM were also variable, with CPGs either recommending its use as a first-line agent when lifestyle modifications are not effective or when insulin therapy is not practicable. Recommendations for antidepressant use were consistent across CPGs analysed. CONCLUSION: Multiple CPGs exist to inform prescribing during pregnancy in Australia, with variation present within CPG quality and recommendations. These findings offer insight into potential sources of variation in maternal and neonatal health outcomes.
Asunto(s)
Profilaxis Antibiótica , Antidepresivos , Diabetes Gestacional , Hipoglucemiantes , Metformina , Guías de Práctica Clínica como Asunto , Humanos , Femenino , Embarazo , Australia , Diabetes Gestacional/tratamiento farmacológico , Metformina/uso terapéutico , Antidepresivos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Rotura Prematura de Membranas Fetales/tratamiento farmacológicoRESUMEN
BACKGROUND: Treatment with antibiotics at the time of preterm prelabor rupture of membranes (PPROM) has been shown to prolong pregnancy. Due to the recurrent shortage of erythromycin, azithromycin has been substituted in the traditional regimen; however, there are little data on optimal dosing. OBJECTIVE: The objective of this study was to determine whether there is a difference in latency from onset of PPROM to delivery in patients who received a single dose of azithromycin compared with a 5-day course. METHODS: This was a single-center, multisite, retrospective, IRB approved analysis of patients admitted with a diagnosis of PPROM. Patients were included if rupture occurred between 22 0/7 and 33 6/7 weeks of gestation and received either a single dose or a 5-day course of azithromycin along with a beta lactam. RESULTS: A total of 376 patients were reviewed with 296 patients included in the final analysis. There was no statistical difference in the primary outcome of latency days in patients who received the 5-day versus the single-dose course (4 vs 5 days, P = 0.641). There was a significantly higher rate of histologic chorioamnionitis in the single-dose course of azithromycin (46.4% vs 62.6%, P = 0.006). CONCLUSIONS AND RELEVANCE: There was no difference in latency for patients who received a 5-day course of azithromycin versus a single dose for the treatment of PPROM. A higher rate of histologic chorioamnionitis was observed in those who received the single-day course. Prospective follow-up studies are needed to confirm these findings.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Embarazo , Recién Nacido , Femenino , Humanos , Antibacterianos/uso terapéutico , Azitromicina/efectos adversos , Corioamnionitis/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Resultado del EmbarazoRESUMEN
OBJECTIVE: Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial agents as treatment for these infections. We aimed to examine the efficacy of intravenous administration of sulbactam/ampicillin (SBT/ABPC) and azithromycin (AZM) for intra-amniotic infection in patients with preterm premature rupture of membranes (PPROM). METHODS: This study followed a single-centered retrospective cohort design. We compared changes in interleukin 6 (IL-6) levels and the load of Ureaplasma species DNA in the amniotic fluid between singleton pregnancy patients with intra-amniotic infection (Group A) and without either intra-amniotic inflammation (IAI) or microbial invasion of the amniotic cavity (MIAC) (Group B) who developed PPROM between week 22, day 0 and week 33, day 6 of gestation and maintained pregnancy for ≥7 d after diagnosis (August 2014 to April 2020). Patients in Group A were treated with SBT/ABPC and AZM, whereas those in Group B were treated with ABPC and AZM or clarithromycin. RESULTS: Thirty-one patients with IAI and 48 patients without either IAI or MIAC at diagnosis of PPROM underwent pregnancy/delivery management at our hospital. Following the study population selection, we evaluated six patients in Group A and 13 patients in Group B. Amniotic fluid IL-6 concentrations at the initial amniocentesis were high, ranging from 11.7 ng/mL to 139.2 ng/mL, indicating a state of severe IAI in all six patients in Group A. In five of the six patients in Group A, the amniotic fluid cultures during the first amniocentesis included Ureaplasma species only. In both groups, the amniotic fluid IL-6 concentration at the follow-up amniocentesis was lower than that at the initial amniocentesis (Group A: follow-up median 3.06 ng/mL [quartiles, 1.75-6.74], initial median 30.53 ng/mL [quartiles, 15.60-67.07], pï¼.03; Group B: follow-up median 0.40 ng/mL [quartiles, 0.18-0.69], initial median 0.96 ng/mL [quartiles, 0.65-1.42], pï¼.005); Group A showed a greater decrease than Group B (p < .001). No difference was found between the microbial loads of Ureaplasma species DNA in the initial and follow-up amniocentesis (p = .13). CONCLUSIONS: In patients with PPROM and intra-amniotic infection, IL-6 levels in the amniotic fluid decreased significantly from before antimicrobial administration to day 7. This decrease is thought to be mainly due to the effects of intravenous AZM. The efficacy of AZM in patients with PPROM needs to be further confirmed via randomized controlled studies in the future.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Embarazo , Recién Nacido , Femenino , Humanos , Corioamnionitis/tratamiento farmacológico , Corioamnionitis/diagnóstico , Estudios Retrospectivos , Nacimiento Prematuro/tratamiento farmacológico , Interleucina-6 , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Antibacterianos/uso terapéutico , Inflamación , Líquido Amniótico , Ureaplasma , ADN , Edad GestacionalRESUMEN
This study compares the effectiveness and safety of oxytocin infusion against oral misoprostol for inducing labour in pregnant women with term prelabor membrane rupture. We randomized 173 pregnant women presenting with term prelabor rupture of membranes (PROM) at Ain Shams University Maternity Hospital into Group A (underwent induction of labor (IOL) by 25µg misoprostol oral tablet every 4 h, for maximum 5 doses) and an identical Group B: (underwent IOL by oxytocin infusion according to the hospital protocol). Our primary outcome was rate of vaginal delivery within 24 h, while the secondary outcomes included the time till active phase, induction to delivery interval, maternal pyrexia, nausea and vomiting, fetal distress, Apgar score, birth weight, and neonatal intensive care unit admission. Both groups showed high rates of vaginal delivery (82.4% & 87.1% for misoprostol group and oxytocin group respectively) with no significant difference between the two groups (p=0.394). However, patients induced by misoprostol took significantly less time to reach active phase with a shorter induction to delivery interval as compared to patients induced with oxytocin. This difference was clear in multiparous women, but not observed in primiparous women when subgroup analysis was done. No significant difference was found as regards other outcomes. Our study showed that both oral misoprostol and oxytocin are effective and safe for IOL in patients with PROM, with shorter induction-delivery interval in patients induced by oral misoprostol, an effect that is clear in multiparous but not primiparous women. TRIAL REGISTRATION: NCT05215873, on 31/01/2022, "retrospectively registered".
Asunto(s)
Rotura Prematura de Membranas Fetales , Misoprostol , Oxitócicos , Recién Nacido , Femenino , Embarazo , Humanos , Misoprostol/efectos adversos , Oxitocina , Oxitócicos/efectos adversos , Mujeres Embarazadas , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Trabajo de Parto Inducido/métodosAsunto(s)
Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Recién Nacido , Femenino , Humanos , Antibacterianos/uso terapéutico , Rotura Prematura de Membranas Fetales/diagnóstico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/epidemiologíaAsunto(s)
Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Recién Nacido , Femenino , Humanos , Antibacterianos/uso terapéutico , Rotura Prematura de Membranas Fetales/diagnóstico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/epidemiología , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/prevención & controlRESUMEN
Infections are common in obstetric care and often require specific antibiotics, depending on the infection site and prevailing organisms. Summaries of antibiotic recommendations and treatment algorithms are provided for the following conditions: routine labor, group B streptococcus prophylaxis, preterm prelabor rupture of membranes, operative vaginal delivery, cesarean delivery, obstetric anal sphincter lacerations, chorioamnionitis, postpartum endometritis, infections of the urinary tract, and bacterial endocarditis prophylaxis.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Trabajo de Parto , Embarazo , Femenino , Recién Nacido , Humanos , Antibacterianos/uso terapéutico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Parto ObstétricoRESUMEN
BACKGROUND: Preterm prelabor rupture of membranes is a leading cause of preterm birth and is responsible for 18% to 20% of perinatal deaths in the United States. An initial course of antenatal corticosteroids has been shown to reduce morbidity and mortality in patients with preterm prelabor rupture of membranes. For patients who remain undelivered for 7 days or more after the initial course of antenatal corticosteroids, it is uncertain whether a booster course of antenatal corticosteroids reduces neonatal morbidity or increases the infection risk. The American College of Obstetricians and Gynecologists has concluded that the current evidence is insufficient to make a recommendation. OBJECTIVE: This study aimed to evaluate if a single booster course of antenatal corticosteroids improves neonatal outcomes after preterm prelabor rupture of membranes. STUDY DESIGN: We conducted a multicenter, placebo-controlled randomized clinical trial. The inclusion criteria were preterm prelabor rupture of membranes, gestational age of 24.0 to 32.9 weeks, singleton, initial antenatal corticosteroid course administered at least 7 days before randomization, and planned expectant management. Consenting patients were randomized in gestational age blocks to either receive booster antenatal corticosteroids (12 mg betamethasone every 24 hours for 2 days) or a saline placebo. The primary outcome was composite neonatal morbidity or death. A sample size of 194 patients was calculated to yield 80% power at P<.05 to detect a reduction in primary outcome from 60% in placebo group to 40% in antenatal corticosteroids group. RESULTS: From April 2016 through August 2022, 194 patients consented and were randomized (47% of 411 eligible patients). Intent-to-treat analysis was performed on 192 patients (2 placebo patients left hospital, outcomes unknown). The groups had similar baseline characteristics. The primary outcome occurred in 64% of patients who received booster antenatal corticosteroids vs in 66% of patients who received the placebo (odds ratio, 0.82; 95% confidence interval, 0.43-1.57; gestational age-stratified Cochran-Mantel-Haenszel test). Individual components of the primary outcome and secondary neonatal and maternal outcomes were not significantly different between the antenatal corticosteroids and placebo groups. Specifically, chorioamnionitis (22% vs 20%), postpartum endometritis (1% vs 2%), wound infections (2% vs 0%), and proven neonatal sepsis (5% vs 3%) were not different between the groups. CONCLUSION: A booster course of antenatal corticosteroids at least 7 days after the first antenatal corticosteroids course in patients with preterm prelabor rupture of membranes did not improve neonatal morbidity or any other outcome in this adequately-powered, double-blind randomized clinical trial. Booster antenatal corticosteroids did not increase maternal or neonatal infection.
Asunto(s)
Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Embarazo , Recién Nacido , Humanos , Femenino , Lactante , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Nacimiento Prematuro/prevención & control , Corticoesteroides/efectos adversos , Betametasona/efectos adversos , Edad Gestacional , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/epidemiología , Rotura Prematura de Membranas Fetales/prevención & controlRESUMEN
BACKGROUND: Prophylactic antibiotic use in preterm premature rupture of membranes is associated with significantly reduced intra-amniotic infection and improved neonatal outcome, although data are insufficient to determine the optimal antibiotic regimen. Ampicillin resistance has changed the epidemiology of neonatal sepsis. OBJECTIVE: This study aimed to determine the efficacy of two antibiotic regimens in prolonging the latency period in women with preterm premature rupture of membranes. STUDY DESIGN: This randomized-controlled trial was conducted in 3 tertiary university-affiliated hospitals. A total of 124 women with preterm premature rupture of membranes at <37 weeks of gestation were randomized into two antibiotic prophylactic protocols: ampicillinâ¯+â¯roxithromycin and cefuroximeâ¯+â¯roxithromycin. The latency period length, neonatal adverse outcomes, and maternal infectious morbidity, including intrauterine infection, intrapartum fever, postpartum antibiotic treatment, endometritis, and wound infection, were measured and compared. RESULTS: Maternal infectious morbidity was higher in the ampicillin group than in the cefuroxime group (17.7% vs 6.5%; 1-sided P value =.048). The pathogen distribution among placenta, membrane, cord, and uterine cultures differed between the groups (P=.017). Enterobacteriaceae spp. cultures were identified in 68.6% of the cultures in the ampicillin group and 43.2% in the cefuroxime group (P=.036). The composite neonatal adverse outcome was higher in the ampicillin group than in the cefuroxime group (55 [88.7%] vs 46 [74.2%]; 1-sided P value =.03). The proportion of primiparas with a latency period >4 days was significantly higher in the cefuroxime group than in the ampicillin group (odds ratio, 3.69; 95% confidence interval, 1.175-11.607; P=.025). CONCLUSION: In combination with roxithromycin, the use of cefuroxime, as a prophylactic in women with premature rupture of membranes at <37 weeks of gestation, showed longer pregnancy in primiparas and less maternal and neonatal morbidity than the use of ampicillin. Further larger studies are needed to support our results.
Asunto(s)
Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Roxitromicina , Embarazo , Recién Nacido , Femenino , Humanos , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/epidemiología , Cefuroxima , Antibacterianos/uso terapéutico , Ampicilina , Nacimiento Prematuro/prevención & controlRESUMEN
BACKGROUND: Preterm birth (PTB) is one of the leading causes of neonatal mortality and morbidity worldwide. A shortened cervix is a recognised risk factor for PTB, and amniotic fluid sludge (AFS) diagnosed on ultrasound may be suggestive of underlying inflammation or infection. AIMS: The aim is to determine if azithromycin, administered in cases of a shortened cervix, results in prolongation of gestation with improvements in neonatal outcomes. MATERIALS AND METHODS: We performed a retrospective cohort study at three tertiary maternity services in Melbourne, Australia, between 2015 and 2020. Women with a singleton pregnancy were included if they had a cervical length of 15 mm or less at 13-24 weeks' gestation, with or without AFS. Exclusion criteria comprised multiple pregnancy, major fetal congenital anomaly, placenta praevia, prelabour premature rupture of membranes, vaginal bleeding and/or clinical signs suggestive of chorioamnionitis at the time of diagnosis of the short cervix. The results of antibiotic treatment with azithromycin were compared to those of no antibiotic treatment. The outcomes of interest were PTB, prelabour premature rupture of membranes (PPROM), chorioamnionitis and neonatal morbidity. RESULTS: A total of 374 women were included in the study, of whom 129 received azithromycin and 245 received no antibiotics. When adjusting for potential confounders, the adjusted risk of PTB overall was higher in the treatment group (adjusted hazard ratio 1.36 (95% confidence interval 1.04-1.77) P = 0.023) with no differences found for PPROM, chorioamnionitis or neonatal morbidity. CONCLUSION: These data do not support the routine use of azithromycin in women with a short cervix, including those with AFS detected on ultrasound.
Asunto(s)
Corioamnionitis , Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Femenino , Embarazo , Recién Nacido , Humanos , Azitromicina/uso terapéutico , Nacimiento Prematuro/etiología , Corioamnionitis/tratamiento farmacológico , Corioamnionitis/etiología , Estudios de Cohortes , Aguas del Alcantarillado , Líquido Amniótico , Estudios Retrospectivos , Cuello del Útero/diagnóstico por imagen , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVE: The aim of this study was to evaluate the association between antibiotic prophylaxis and adverse perinatal outcomes in premature rupture of membranes. METHODS: This retrospective cohort included pregnant women with premature rupture of membranes (between 24 and 33+6 weeks) who used or did not use prophylactic antibiotics. Pearson's chi-square (χ²) test, Student's t-test, and binary logistic regression were used for statistical analysis. RESULTS: A significant effect was observed in patients with premature rupture of membranes using prophylactic antibiotics regarding amniotic fluid index (p=0.007), deepest vertical pocket (p=0.049), duration of antibiotic therapy (p≤0.001), C-reactive protein level upon admission (p≤0.001), leukocyte count upon admission (p=0.007), and length of stay in neonatal intensive care (p=0.047). A significant association was observed between the abovementioned patients and surfactant use during the neonatal period (p=0.04). A higher prevalence of surfactant use was noted in these patients (20.0 vs. 8.7%; p=0.04). CONCLUSION: No association was found between antibiotic prophylaxis and the presence of adverse perinatal outcomes in pregnant women with premature rupture of membranes between 24 and 33+6 weeks of gestation.
Asunto(s)
Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Profilaxis Antibiótica , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Rotura Prematura de Membranas Fetales/prevención & control , Estudios Retrospectivos , Nacimiento Prematuro/prevención & control , Antibacterianos/uso terapéutico , Edad Gestacional , Resultado del EmbarazoRESUMEN
AIM: To examine whether biochemical surveillance vs clinical observation of term infants with prolonged rupture of membranes as a risk factor for early-onset sepsis is associated with differences in patient trajectories in maternity and neonatal intensive care units. METHODS: A retrospective study of live-born infants with gestational age ≥ 37 + 0 weeks born after prolonged rupture of membranes (≥24 h) in four Norwegian hospitals 2017-2019. Two hospitals used biochemical surveillance, and two used predominantly clinical observation to identify early-onset sepsis cases. RESULTS: The biochemical surveillance hospitals had more C-reactive protein measurements (p < 0.001), neonatal intensive care unit admissions (p < 0.001) and antibiotic treatment (p < 0.001). Hospitals using predominantly clinical observation initiated antibiotic treatment earlier in infants with suspected early-onset sepsis (p = 0.04) but not in infants fulfilling early-onset sepsis diagnostic criteria (p = 0.09). There was no difference in antibiotic treatment duration (p = 0.59), fraction of infants fulfilling early-onset sepsis diagnostic criteria (p = 0.49) or length of hospitalisation (p = 0.30), and no early-onset sepsis-related adverse outcomes. CONCLUSION: The biochemical surveillance hospitals had more C-reactive protein measurements, but there was no difference in antibiotic treatment duration, early-onset sepsis cases, length of hospitalisation or adverse outcomes. Personnel resources needed for clinical surveillance should be weighed against the limitation of potentially painful procedures.
Asunto(s)
Rotura Prematura de Membranas Fetales , Sepsis , Recién Nacido , Humanos , Lactante , Embarazo , Femenino , Estudios Retrospectivos , Proteína C-Reactiva , Parto , Antibacterianos/uso terapéutico , Sepsis/diagnóstico , Sepsis/epidemiología , Rotura Prematura de Membranas Fetales/inducido químicamente , Rotura Prematura de Membranas Fetales/tratamiento farmacológicoRESUMEN
BACKGROUND: Postpartum endometritis (PPE) is 12-25 times more common following caesarean sections (CS) performed after labour onset than after vaginal delivery. Risk factors for PPE include prolonged rupture of membranes (ROM), chorioamnionitis, prolonged labour, multiple cervical examinations and Group B Streptococcus colonisation of the lower genital tract. AIMS: We compared uterine culture results and microbial antibiotic susceptibility according to ROM duration in emergent intrapartum CS. Secondary outcomes included PPE incidence, and identification of clinical and microbiological predictors of infectious postpartum morbidity. MATERIALS AND METHODS: In a retrospective case series of intrapartum CS in which uterine culture was performed, associations with postpartum outcomes including postpartum microbiology are reported. The results were stratified by the duration of ROM (treated as a categorical variable). Univariate analysis was performed. RESULTS: Positive uterine cultures were identified in 15% of emergent CS and correlated with prolonged ROM. Escherichia coli was the sole pathogen isolated in preterm CS; the ampicillin resistance rate was 75%. Among women with positive uterine cultures, rates were increased for postpartum fever, re-admission, PPE and surgical site infection. Cultures obtained from postpartum infections correlated with pathogens isolated from uterine cultures during CS in 46.1% of women. Positive uterine culture was related to umbilical cord pH < 7.1 (P = 0.017). CONCLUSIONS: Obtaining routine intrauterine culture during intrapartum CS is of low risk and low cost, and relatively easy to perform. Further research should investigate clinical and health economic impacts of obtaining intrauterine culture during CS, influences on postpartum antibiotic treatment, and maternal and neonatal morbidity.
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Rotura Prematura de Membranas Fetales , Complicaciones del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Cesárea/efectos adversos , Estudios Retrospectivos , Parto Obstétrico , Rotura Prematura de Membranas Fetales/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Complicaciones del Embarazo/tratamiento farmacológicoRESUMEN
The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.
Asunto(s)
Diabetes Gestacional , Rotura Prematura de Membranas Fetales , Nacimiento Prematuro , Embarazo , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/prevención & control , Nacimiento Prematuro/tratamiento farmacológico , Nacimiento Prematuro/epidemiología , Inositol/farmacología , Inositol/uso terapéutico , Diabetes Gestacional/tratamiento farmacológico , Diabetes Gestacional/prevención & control , Rotura Prematura de Membranas Fetales/tratamiento farmacológicoRESUMEN
Neonatal infections are responsible for 20% of neonatal deaths yearly. In this review, we focused on the origins of the commoner neonatal infections, and we define the role of obstetricians. Regarding group B Streptococcus, a key measure for the prevention of neonatal infection is the vaginal-rectal culture screening at term pregnancy. Intravenous penicillin is the first-line prophylaxis at the start of labor, with intravenous ampicillin as an alternative. First-generation cephalosporins or clindamycin are recommended in case of penicillin allergy. Concerning urinary tract infections (UTIs), guidelines recommend complete urinalysis and urine culture in the first trimester of pregnancy for the screening of asymptomatic bacteriuria. For lower UTIs, guidelines recommend nitrofurantoin as first-choice antibiotic. Amoxicillin or cefalexin are second-line antibiotics. For upper UTIs, guidelines recommend cephalexin per os as first line. Candida spp. colonization affects 20% of pregnant women; however, congenital fetal candidosis and Candida amnionitis are rare. First-line treatment in case of symptomatic vaginitis during pregnancy or asymptomatic colonization during the third trimester is vaginal clotrimazole. Fluconazole is not approved in pregnancy, especially during the first trimester. Genital mycoplasmas colonization during pregnancy is usually asymptomatic and associated with bacterial vaginosis. Colonization is related to neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pneumonia, chorioamnionitis, and sepsis. Macrolides are the first-line treatment along with lactobacillus supplementation. In cases of preterm premature rupture of membranes or preterm labor, ceftriaxone, clarithromycin, and metronidazole are required to prevent intra-amniotic infection. Intra-amniotic infection affects 1 to 5% of deliveries at term and one-third of preterm ones and is associated with perinatal death, early-onset neonatal sepsis, RDS, BPD, pneumonia, meningitis, and prematurity-related diseases. Guidelines recommend a combination of ampicillin and gentamicin, and in case of caesarean section, an additional dose of clindamycin or metronidazole is required. In conclusion, obstetricians should be aware that the treatment of maternal infection during pregnancy can prevent potentially lethal infections in the newborn. KEY POINTS: · Part of neonatal infections starts from maternal infections that must be treated during pregnancy.. · Streptococcus group B and asymptomatic bacteriuria should be investigated in pregnancy and treated.. · Mycoplasma and ureaplasma vaginal colonization during pregnancy is related to negative neonatal outcomes..