Background: We conducted a one-year, retrospective, mirror-image study to investigate the clinical effectiveness and safety of aripiprazole once monthly (AOM) in patients with bipolar disorder (BD). We compared pretreatment conditions with outcomes after 12 months of AOM treatment. Methods: Seventy-five bipolar patients were recruited from 12 hospitals in Korea. We included 75 patients with BD who had received at least three AOM treatments from September 2019 to September 2022 and had accessible electronic medical record (EMRs) for the year before and after the baseline visit. Results: The overall number of mood episodes significantly decreased from a mean of 1.5 +/- 1.2 episodes preAOM to 0.5 +/- 1.2 episodes post-AOM. Manic episodes significantly decreased from 0.8 +/- 0.8 episodes preAOM to 0.2 +/- 0.5 episodes post-AOM, and depressive episodes significantly decreased from 0.5 +/- 0.8 episodes pre-AOM to 0.2 +/- 0.6 episodes post-AOM (p = 0.017). Moreover, the number of psychiatric medications and pills and the proportion of patients treated with complex polypharmacy were significantly decreased postAOM. Limitations: The small sample size was insufficient to fully represent the entire population of individuals with BD, and potential selection bias was introduced due to only including subjects who received AOM three or more times. Conclusion: The results of this study suggest that AOM can reduce mood episode relapse and may be clinically beneficial in the treatment of BD patients, potentially reducing issues associated with polypharmacy in some individuals.

Angiogenesis is mainly regulated by the delivery of VEGF-dependent signaling to cells. However, the angiogenesis mechanism regulated by VEGF-induced miRNA is still not understood. After VEGF treatment in HUVECs, we screened the changed miRNAs through small-RNA sequencing and found VEGF-induced miR-4701-3p. Furthermore, the GFP reporter gene was used to reveal that TOB2 expression was regulated by miR-4701-3p, and it was found that TOB2 and miR-4701-3p modulation could cause angiogenesis in an in-vitro angiogenic assay. Through the luciferase assay, it was confirmed that the activation of the angiogenic transcription factor MEF2 was regulated by the suppression and overexpression of TOB2 and miR-4701-3p. As a result, MEF2 downstream gene mRNAs that induce angiogenic function were regulated. We used the NCBI GEO datasets to reveal that the expression of TOB2 and MEF2 was significantly changed in cardiovascular disease. Finally, it was confirmed that the expression of circulating miR-4701-3p in the blood of myocardial infarction patients was remarkably increased. In patients with myocardial infarction, circulating miR-4701-3p was increased regardless of age, BMI, and sex, and showed high AUC levels in specificity and sensitivity analysis (AUROC) (AUC = 0.8451, 95 % CI 0.78-0.90). Our data showed TOB2-mediated modulation of MEF2 and its angiogenesis by VEGF-induced miR-4701-3p in vascular endothelial cells. In addition, through bioinformatics analysis using GEO data, changes in TOB2 and MEF2 were revealed in cardiovascular disease. We suggest that circulating miR-4701-3p has high potential as a biomarker for myocardial infarction.

Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconiumstained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconiumstained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.

Bo-Mi Jung, MS, Su-Mi Hyun, MA, Bo-Hyun Yoon, MD, PhD, Jye-Heon Song, MD, Kyung-Min Kim, MD, Hyoung-Yeon Kim, BS, Deuk-Sil Oh, MS, Seok-Myun Lee, MS. Mood Emot 2023;21:1-7. https://doi.org/10.35986/me.2023.21.1.1

To examine the effect of antenatal administration of clarithromycin on the eradication of intra-amniotic infection with ureaplasmas. This was based on the results of culture for ureaplasmas of neonatal gastric fluid obtained within 24 hours of birth. We also compared the effect of clarithromycin with other antibiotics. The study population consisted of 64 singleton pregnant women with preterm prelabor rupture of membranes (gestational age: 18-33 weeks) and a positive amniotic fluid culture for ureaplasmas. The study population was divided into two groups according to the antenatal use of clarithromycin within one day of amniocentesis (clarithromycin group [n=29] and non-clarithromycin groups [n=35], respectively). Amniotic fluid was obtained by amniocentesis and neonatal gastric fluid was by nasogastric intubation within 24 hours of birth and cultured for ureaplasmas. 1) Ureaplasmas were isolated in 38% (11/29) of gastric fluid obtained from preterm newborns born to mothers with intra-amniotic infection with these microorganisms in the clarithromycin group; 2) however, ureaplasmas were isolated in 66% (23/35) of those born to mothers with infection with these microorganisms in the non-clarithromycin group (38% vs 66%, p< 0.05); 3) The use of clarithromycin and low amniotic fluid WBC count (< 19 cells/mm3) was significantly associated with the absence of ureaplasmas in gastric fluid after the adjustment of gestational age at amniocentesis (use of clarithromycin: odds ratio 0.27, [95% CI 0.09–0.81], P< 0.05; AF WBC count < 19 cell/mm3, odds ratio 0.12, [95% CI 0.02–0.71], P< 0.05). Ureaplasmas were not isolated in two-thirds of gastric fluid of preterm newborns born to mothers with intra-amniotic infection with ureaplasmas and who received clarithromycin. The use of clarithromycin and low amniotic fluid WBC count were associated with the 73% reduction in the rate of positive culture for ureaplasmas in the gastric fluid of these newborns.

This study aimed to assess the association between maternal blood neutrophil-to-lymphocyte ratio (NLR) and microbial invasion of the amniotic cavity (MIAC) and to compare the diagnostic performance of NLR with that of maternal serum C-reactive protein (CRP) levels for identifying MIAC in patients with preterm prelabor rupture of membranes (pPROM). This study included 154 patients with pPROM who underwent transabdominal amniocentesis (gestational age: 20–33 weeks) to evaluate the microbiologic status of amniotic cavity and/or fetal lung maturity. The amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. MIAC was defined as a positive AF culture. Maternal blood samples were collected within 24 hours of amniocentesis, and serum levels of leukocyte differentials and CRP were measured. 1) The rate of MIAC was 36.4% (56/154) in patients with pPROM; 2) the median NLR and CRP levels in the patients with MIAC were significantly higher than those without MIAC (NLR: 6.8 [95% CI, 7.0–9.8] vs. 5.0 [95% CI, 5.3–6.6], P < 0.05; CRP levels: 0.6 mg/dL [95% CI, 0.8–1.3] vs. 0.3 mg/dL [95% CI, 0.5–0.9], P < 0.05); 3) the area under the curve of NLR was similar to that of CRP (0.7 [95% CI, 0.6–0.8] vs. 0.6 [95% CI 0.5–0.7], P=0.59); 4) the NLR ≥ 6.2 had sensitivity of 64.3% (95% CI: 50.4–76.6), specificity of 65.3% (95% CI, 55.0–74.6), positive likelihood ratio of 1.9 (95% CI, 1.3–2.6), and negative likelihood ratio of 0.55 (95% CI, 0.4–0.8); 5) the rate of MIAC was 54.3% (19/35) in patients with high NLR (≥ 6.2)/high CRP (≥ 0.7mg/dL), 48.6% (17/35) in those with high NLR/low CRP, 40.0% (8/20) in those with low NLR/high CRP, and 18.8% (12/64) in those with low NLR/low CRP (odds ratio [OR], 5.15 [95% CI, 2.06–12.84], 4.09 [1.64–10.20] and 2.89 [0.97–8.62] compared to patients with low NLR/low CRP, respectively). An elevated NLR was associated with the presence of MIAC in patients with pPROM. The diagnostic performance of NLR was similar to that of CRP levels. However, MIAC was present in 18.8% of patients with low NLR/low CRP levels.

The minimally invasive application of photoacoustic (optoacoustic) tomography (PAT) has been mainly focused on gastrointestinal endoscopy and the imaging of cardiovascular and reproductive systems, such as the uterus, ovaries, and prostate, in relation to the diagnosis of atherosclerotic plaques (e.g., in coronary arteries) and reproductive cancers. However, the miniature probe technology involved could also make a considerable contribution to the diagnosis and post-treatment follow-ups of urinary diseases. PAT can provide a variety of anatomical, functional, and molecular information that is not producible with conventional imaging methods, such as MRI and ultrasound. Among the related clinical issues, the development of a new diagnostic paradigm for the early detection of bladder cancer is urgently needed, because it is known to be very aggressive and lethal if found after stage 2 (T2). In this study, we developed a transurethral photoacoustic and ultrasonic endoscopic probe with an outer diameter of 2.8 mm to contribute to the early diagnosis of bladder cancer in clinical urology. From a live rabbit, we successfully acquired the first high-resolution 3D vasculature map of more than 50% of the bladder wall, which we believe is a completely new type of image information never acquired before from a vertebrate urinary system.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Introduction Olanzapine (OLA) is a common first-prescribed antipsychotic and has shown favorable efficacy in acutely exacerbated patients with schizophrenia. The mixed receptor activity of OLA and its greater affinity for serotonin 5-HT2A rather than dopamine D2 receptors are similar to those of clozapine. Pharmacokinetically, OLA is metabolized mainly by hepatic cytochrome enzyme P450 1A2 (CYP1A2). Because risks of antipsychotic polypharmacy include increased drug-drug interactions, pharmacokinetic considerations are important for selection of antipsychotics to be combined. Due to its pharmacological characteristics, amisulpride (AMI), another atypical antipsychotic with proven efficacy, is a promising adjuvant agent of special interest. AMI is unlikely to interact with other drugs due to the low plasma protein binding and metabolism and does not affect the activity of the CYP system. Furthermore, AMI is highly selective for dopamine D2/D3 receptors; has minimal or no affinity for D1, D4, or D5 receptors. Despite the potential benefits of the combination of OLA and AMI, only a few open-label studies have been conducted, and no randomized clinical trial has been performed to date to examine the efficacy and tolerability of the combination. Hence, the goals of this study were to test the hypothesis that AMI augmentation would improve psychotic symptoms and be well tolerated in schizophrenic patients who showed poor response to OLA monotherapy. Objectives The purpose of this study was to compare the efficacy and tolerability of continued olanzapine (OLA) versus amisulpride (AMI) augmentation in schizophrenic patients with poor response to OLA monotherapy. Methods The present 4-week, randomized, rater-blinded study included 25 patients with schizophrenia who were partially or completely unresponsive to treatment with OLA monotherapy. Eligible subjects were randomly assigned at a 1:1 ratio to continuation of OLA monotherapy (OLA group) or OLA with AMI augmentation (AMI group). Efficacy was primarily evaluated using the Positive and Negative Syndrome Scale (PANSS) at baseline and at 1, 2, and 4 weeks. Results The changes in PANSS total score and PANSS-positive subscale score were significantly different (p < 0.05) between the OLA and AMI groups. The differences between the two groups in PANSS-negative subscale, PANSS-general subscale, Brief Psychiatric Rating Scale, and Clinical Global Impression-Severity (CGI-S) scale scores were not statistically significant. Conclusions AMI augmentation could be an effective strategy for patients with schizophrenia who show inadequate early response to OLA monotherapy. Disclosure of Interest W.-M. Bahk Grant / Research support from: Handok Pharmaceuticals, Seoul, Korea, Y. S. Woo: None Declared, S.-Y. Park: None Declared, B.-H. Yoon: None Declared, S.-M. Wang: None Declared, M.-D. Kim: None Declared

We thank Drs Jiang and Li for their interest in our work, and we are glad to respond to the questions. The gold standard for the diagnoses of intraamniotic infection and intraamniotic inflammation is the analysis of amniotic fluid. An extensive body of literature shows that neither analysis of maternal blood nor analysis of cervicovaginal fluid has sufficient accuracy to replace amniotic fluid analysis for the diagnosis of intraamniotic infection/inflammation. Therefore, amniocentesis is offered at the Seoul National University Hospital to patients admitted with the diagnosis of preterm labor, cervical insufficiency, and increased uterine contractility, even in the absence of cervical changes.1Lee S.E. Romero R. Park C.W. Jun J.K. Yoon B.H. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency.Am J Obstet Gynecol. 2008; 198: 633.e1-633.e8Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar,2Kim S.M. Romero R. Lee J. et al.The frequency and clinical significance of intra-amniotic inflammation in women with preterm uterine contractility but without cervical change: do the diagnostic criteria for preterm labor need to be changed?.J Matern Fetal Neonatal Med. 2012; 25: 1212-1221Crossref PubMed Scopus (37) Google Scholar The rationale is 2-fold: that intraamniotic infection/inflammation is present in a fraction of patients diagnosed with each obstetrical syndrome and that infection or inflammation can be successfully treated after accurate diagnosis, as reported by our group.3Oh K.J. Romero R. Park J.Y. et al.Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.Am J Obstet Gynecol. 2019; 221: 140.e1-140.e18Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar,4Oh K.J. Romero R. Kim H.J. et al.The role of intraamniotic inflammation in threatened midtrimester miscarriage.Am J Obstet Gynecol. 2022; 227: 895.e1-895.e13Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar The practice at Seoul National University Hospital was described in the study design of our article.4Oh K.J. Romero R. Kim H.J. et al.The role of intraamniotic inflammation in threatened midtrimester miscarriage.Am J Obstet Gynecol. 2022; 227: 895.e1-895.e13Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Patients could consent or decline a diagnostic procedure and also consent or decline to participate in an observational study, which asked patients to donate a sample for research purposes. Genetic studies of amniotic fluid are not part of the standard workup in cases of threatened miscarriage. Regarding cervical length follow-up, we did not have a standardized protocol for this procedure, and clinical management was left to the discretion of the treating clinicians. The third question was about the performance of cervical cerclage after the exclusion of intraamniotic infection/inflammation in patients with cervical dilatation. We agree with Drs Jiang and Li that cerclage is indicated in patients with cervical insufficiency. However, we noted that the criterion for enrollment in our study was patients with threatened second-trimester miscarriage, and the inclusion required regular uterine contractility.4Oh K.J. Romero R. Kim H.J. et al.The role of intraamniotic inflammation in threatened midtrimester miscarriage.Am J Obstet Gynecol. 2022; 227: 895.e1-895.e13Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar Moreover, the diagnosis of cervical insufficiency is made when individuals experience painless cervical dilatation in the absence of regular uterine contractions. Concerning the question of amniocentesis and cervical cerclage, our view is that amniocentesis should be performed before the placement of an emergency cerclage, given the high prevalence of intraamniotic infection/inflammation,1Lee S.E. Romero R. Park C.W. Jun J.K. Yoon B.H. The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency.Am J Obstet Gynecol. 2008; 198: 633.e1-633.e8Abstract Full Text Full Text PDF PubMed Scopus (159) Google Scholar,5Romero R. Gonzalez R. Sepulveda W. et al.Infection and labor. VIII. Microbial invasion of the amniotic cavity in patients with suspected cervical incompetence: prevalence and clinical significance.Am J Obstet Gynecol. 1992; 167: 1086-1091Abstract Full Text PDF PubMed Scopus (240) Google Scholar the poor outcome of patients who undergo cerclage despite intraamniotic infection/inflammation,6Mönckeberg M. Valdés R. Kusanovic J.P. et al.Patients with acute cervical insufficiency without intra-amniotic infection/inflammation treated with cerclage have a good prognosis.J Perinat Med. 2019; 47: 500-509Crossref PubMed Scopus (19) Google Scholar and the encouraging results of our previous studies that demonstrated that intraamniotic infection/inflammation can be treated.3Oh K.J. Romero R. Park J.Y. et al.Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency.Am J Obstet Gynecol. 2019; 221: 140.e1-140.e18Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar Moreover, the authors asked about the long-term follow-up of survivors. Of the 15 patients diagnosed with intraamniotic inflammation in this study, 9 delivered before 22 weeks of gestation, and 5 delivered after 34 weeks of gestation.4Oh K.J. Romero R. Kim H.J. et al.The role of intraamniotic inflammation in threatened midtrimester miscarriage.Am J Obstet Gynecol. 2022; 227: 895.e1-895.e13Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar We described that those 5 newborns survived without morbidity, as shown in Tables 1 and 2. In addition, we described that one of the limitations of this study was the "lack of follow-up beyond the neonatal period."4Oh K.J. Romero R. Kim H.J. et al.The role of intraamniotic inflammation in threatened midtrimester miscarriage.Am J Obstet Gynecol. 2022; 227: 895.e1-895.e13Abstract Full Text Full Text PDF PubMed Scopus (2) Google ScholarTable 1Characteristics and outcomes of 4 patients with intraamniotic inflammation who underwent follow-up amniocentesisGestational age (weeks)Cervix dilatation (cm)aCervical dilatation was determined by visual examination at the time of sterile speculum examination.Analysis of amniotic fluid (initial amniocentesis)Interval between initial amniocentesis and resolution (days)Total duration of antibiotics (days)Acute histologic chorio-amnionitis and funisitisOutcomeCase No.Amnio-centesisDeliveryCulturePolymerase chain reaction for Ureapla-sma spp.Matrix metallo-proteinase-8 (ng/mL)White blood cell count (cells/mm3)Matrix metallo-proteinase-8 rapid test116+240+61.5NegNeg117.710Pos1426Neg/NegNeonatal survival without morbidity216+137+10NegNeg986.0135N/A3158N/ARupture of membranes at 17+5 weeks, Ureaplasma urealyticum isolated by PCR in the follow-up amniocentesis performed on 18+1 week, and severe oligohydramnios persisted for more than 2 weeks.Neonatal survival without morbidity317+335+11.5NegNeg1815.6144N/A3473Pos/NegReadmission twice due to preterm labor or low abdominal pain, induction of labor at 35 weeksNeonatal survival without morbidity416+228+30NegNeg192.41Pos4686Neg/NegRupture of membranes (2 hours after initial amniocentesis), delivery due to placental abruption, newborn developed respiratory distress syndrome, bronchopulmonary dysplasia, and hypothyroidismN/A, not assessed; Neg, negative; PCR, polymerase chain reaction; Pos, positive.a Cervical dilatation was determined by visual examination at the time of sterile speculum examination. Open table in a new tab Table 2Characteristics and outcomes of 4 patients with intraamniotic inflammation who delivered after 1 week of amniocentesis without a follow-up amniocentesisGestational age (weeks)Cervix dilatation (cm)aCervical dilatation was determined by visual examination at the time of sterile speculum examination.Analysis of amniotic fluidDuration of antibiotics (days)Acute histologic chorio-amnionitis and funisitisOutcomeCase No.Amnio-centesisDeliveryCulturePolymerase chain reaction for Ureaplasma spp.Matrix metallo-proteinase-8 (ng/mL)White blood cell count (cells/mm3)Matrix metallo-proteinase-8 rapid kit519+439+23NegNeg32.51N/A6Pos/PosSurvival without morbidity615+634+30NegNeg381.66N/A18N/ARupture of membranes at 16+1 weeks, severe oligohydramnios, neonatal survival without morbidity718+321+43NegNeg1785.2702Pos23Neg/NegRupture of membranes on 18+4 weeks, persistent severe oligohydramnios, patient wanted termination819+420+50NegNeg1082.81460N/A8Pos/NegFever (38.6°C), severe oligohydramnios detected on 20+3 weeks, fetal death identified at 20+5 weeksN/A, not assessed; Neg, negative; Pos, positive.a Cervical dilatation was determined by visual examination at the time of sterile speculum examination. Open table in a new tab N/A, not assessed; Neg, negative; PCR, polymerase chain reaction; Pos, positive. N/A, not assessed; Neg, negative; Pos, positive. Antibiotic treatment for intra-amniotic inflammation in threatened midtrimester miscarriageAmerican Journal of Obstetrics & GynecologyVol. 228Issue 4PreviewA pregnancy loss in the second trimester of pregnancy, known as midtrimester miscarriage (MTM), is a hard and sad experience, with individuals developing adverse effects on physical and mental health. There are several known causes of MTM, including chromosome problems, infection, antiphospholipid syndrome, and genetic, structural, and anatomic reasons.1 Recently, Oh et al2 examined the frequency of intra-amniotic inflammation or infection and the effect of antibiotics in 17 patients with threatened MTM and intact membranes before 20 weeks of gestation. Full-Text PDF

BACKGROUND:The assessment and management of patients with threatened midtrimester miscarriage is a clinical challenge because the etiology of this condition is poorly understood.OBJECTIVE:This study aimed to examine the frequency of intraamniotic infection or inflammation and the effect of antibiotics in patients presenting with regular uterine contractions and intact membranes before 20 weeks of gestation.STUDY DESIGN:This retrospective study comprised patients who met the following criteria: (1) singleton gestation, (2) gestational age before 20 weeks, (3) the presence of regular uterine contractions confirmed by a tocodynamometer (8 or more contractions in 60 minutes), (4) intact amniotic membranes, and (5) transabdominal amniocentesis performed for the evaluation of the microbiologic and inflammatory status of the amniotic cavity. Samples of amniotic fluid were cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and polymerase chain reaction was performed to detect Ureaplasma species. Amniotic fluid was tested for white blood cell counts and matrix metalloproteinase-8 concentrations to diagnose intraamniotic inflammation. Patients with intraamniotic inflammation, or intraamniotic infection, were treated with antibiotics (a combination of ceftriaxone, clarithromycin, and metronidazole). Treatment success was defined as the resolution of intraamniotic infection/inflammation at the follow-up amniocentesis or delivery after 34 weeks of gestation.RESULTS:1) Intraamniotic inflammation was present in 88% (15/17) of patients, whereas infection was detectable in only 2 cases; 2) objective evidence of resolution of intraamniotic inflammation after antibiotic treatment was demonstrated in 100% (4/4) of patients who underwent a follow-up amniocentesis; 3) 30% (5/15) of women receiving antibiotics delivered after 34 weeks of gestation (3 of the 5 patients had a negative follow-up amniocentesis, and 2 of the women were without a follow-up amniocentesis); 4) the overall treatment success of antibiotics was 40% (6/15; 4 cases of objective evidence of resolution of intra-amniotic inflammation and 5 cases of delivery after 34 weeks of gestation).CONCLUSION:The prevalence of intraamniotic inflammation in patients who presented with a threatened midtrimester miscarriage was 88% (15/17), and, in most cases, microorganisms could not be detected. Antibiotic treatment, administered to patients with intraamniotic inflammation, was associated with either objective resolution of intraamniotic inflammation or delivery after 34 weeks of gestation in 40% (6/15) of the cases.

Objective To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis. Methods This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system. Results Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation (p < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6-19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15-0.22) in the identification of intra-amniotic infection/inflammation. Conclusions (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.