Chorioamnionitis Research Articles

Clinical and laboratory signs of multiple organ dysfunction in newborns with intraamniotic infection: prospective observational study

INTRODUCTION: Assessment of the severity of the condition of newborns with intra-amniotic infection is extremely important for neonatal intensive care. OBJECTIVE: To study signs of multi-organ dysfunction in newborns with intra-amniotic infection. MATERIALS AND METHODS: 165 newborns who are being treated in the NICU were examined. The weight of the children was 1870 (1480–2550) g, the Apgar score at the first minute was 7 (6–7), at the fifth — 8 (7–8) points. Depending on the gestation period, the children were divided into 4 groups: I — 26–29, II — 30–33, III — 34–37 and IV — 38–40 weeks. In groups I–III, children with respiratory distress syndrome and intraamniotic infection prevailed, and in groups IV — with asphyxia. RESULTS: The maximum score on the NEOMOD scale of the ball is typical for children of groups I and IV: 4 (3–5) and 3 (1–4) points, respectively. The number of leukocytes in group IV newborns on the first day of treatment was statistically significantly higher than in groups II and III: 19.6 (8.5–43.7) vs 12.4 (5.8–33.1) and 12.5 (6.4–32.5), respectively (p = 0.003). Вase excess indicators in group I were statistically significantly lower than in group IV: −7.2 vs −4.2 (p < 0.001). The minimum concentration of C-reactive protein was typical for group I children — 1.7 (1.3–2.2) mg/l, which was significant compared to the indicators of other groups (p < 0.001). CONCLUSIONS: The most pronounced multiple organ dysfunction was observed in newborns with a gestation period of 26–29 and 38–40 weeks, which is confirmed by high scores on the NEOMOD scale, an increase in the number of leukocytes and neutrophil index indicators. Hemodynamic disorders in newborns with a gestation period of 26–29 weeks are the main factor determining the severity of the child's condition and the NEOMOD score.

Impact of antimicrobial stewardship interventions on peripartum antibiotic prescribing in patients with penicillin allergy

Beta-lactam antibiotics (eg, penicillins, cephalosporins, and carbapenems) are preferred for group B streptococcus prophylaxis, intra-amniotic infection, and cesarean surgical site infection prophylaxis. Non-beta-lactam alternatives are associated with inferior efficacy and contribute to higher rates of surgical site infection and longer lengths of stay. Most patients who report a penicillin allergy can tolerate penicillins without any adverse reaction. There are low rates of cross-reactivity between penicillins and other beta-lactams, including cephalosporins and carbapenems. Efforts to evaluate penicillin allergy and promote the use of beta-lactams are needed. This study aimed to evaluate whether an antimicrobial stewardship intervention improved the use of first-line antibiotics for peripartum indications in patients with a reported penicillin allergy, following updates to institutional guidelines. This was a retrospective study of adult patients presenting for vaginal or cesarean delivery at 2 hospitals within a healthcare system. Patients received at least 1 dose of antibiotics for a peripartum indication between May 1, 2018, and October 31, 2018 (preintervention group) and May 1, 2020, to October 31, 2020 (postintervention group). The stewardship intervention bundle, which was implemented between March 2019 and April 2020, included updates to institutional antibiotic guidelines, reclassification of severe penicillin allergy, development of obstetrical prophylaxis and treatment order sets, promotion of allergy referral services, and establishment of a physician champion. The primary outcome was the composite rates of patients with reported penicillin allergy who received a preferred antibiotic for a peripartum indication. The secondary measures included maternal and neonatal outcomes. A total of 192 patients with a history of documented penicillin allergy were evaluated (96 patients in the preintervention group and 96 patients in the postintervention group). Hives were the most commonly reported index symptom in both groups (40/96 [41.7%] vs 39/96 [40.6%]; P=.883). After stewardship interventions, there was a significant increase in the rate of preferred antibiotic use (33/96 [34.3%] vs 81/96 [84.3%]; P<.001). The effect was the greatest in patients with nonsevere allergy (14/76 [18.4%] vs 68/82 [82.9%]; P<.001). There was no difference in the rates of postpartum endometritis, 30-day readmission, 90-day surgical site infection, or neonatal early-onset sepsis between the pre- and postintervention groups. Of note, 1 patient in the postintervention group experienced itching, and another patient developed a rash, both of which resolved with medical management. A comprehensive antibiotic stewardship intervention was associated with a 50% increase in the use of preferred antibiotics for peripartum indications in patients with penicillin allergy. Allergic reactions with first-line beta-lactams were minimal and manageable.

Genomic analysis of Enterococcus faecium strain RAOG174 associated with acute chorioamnionitis carried antibiotic resistance gene: is it time for precise microbiological identification for appropriate antibiotic use?

BackgroundPreterm labor syndrome is associated with high perinatal morbidity and mortality, and intra-amniotic infection is a cause of preterm labor. The standard identification of causative microorganisms is based on the use of biochemical phenotypes, together with broth dilution-based antibiotic susceptibility from organisms grown in culture. However, such methods could not provide an accurate epidemiological aspect and a genetic basis of antimicrobial resistance leading to an inappropriate antibiotic administration. Hybrid genome assembly is a combination of short- and long-read sequencing, which provides better genomic resolution and completeness for genotypic identification and characterization. Herein, we performed a hybrid whole genome assembly sequencing of a pathogen associated with acute histologic chorioamnionitis in women presenting with PPROM.ResultsWe identified Enterococcus faecium, namely E. faecium strain RAOG174, with several antibiotic resistance genes, including vancomycin and aminoglycoside. Virulence-associated genes and potential bacteriophage were also identified in this genome.ConclusionWe report herein the first study demonstrating the use of hybrid genome assembly and genomic analysis to identify E. faecium ST17 as a pathogen associated with acute histologic chorioamnionitis. The analysis provided several antibiotic resistance-associated genes/mutations and mobile genetic elements. The occurrence of E. faecium ST17 raised the awareness of the colonization of clinically relevant E. faecium and the carrying of antibiotic resistance. This finding has brought the advantages of genomic approach in the identification of the bacterial species and antibiotic resistance gene for E. faecium for appropriate antibiotic use to improve maternal and neonatal care.

The yield of procalcitonin and Interleukin-6 in predicting intraamniotic infection in the presence of intrapartum fever: A pilot study.

Intrapartum fever (IF) accompanied by either maternal or foetal tachycardia, elevated WBC, or purulent discharge is classified as "suspected triple 1", the hallmark of intraamniotic infection (IAI). Poor specificity of the clinical diagnosis of IAI results, in retrospect, in the unnecessary treatment of most parturients and neonates. We studied the yield of specific acute phase reactants (APRs): procalcitonin, CRP, IL-6, in detecting bacterial IAI among parturients classified as "suspected triple 1" (cases) compared to afebrile parturients (controls). Procalcitonin, CRP, and IL-6 were all significantly elevated in the cases compared to the controls, yet this by itself was not sufficient for an additive effect in detecting a bacterial infection among parturients clinically diagnosed with "suspected triple 1", as demonstrated by the poor area under the receiver operating characteristic curve of all three APRs.

Thymic stromal lymphopoietin participates in the host response to intra-amniotic inflammation leading to preterm labor and birth

The aim of this study was to establish the role of thymic stromal lymphopoietin (TSLP) in the intra-amniotic host response of women with spontaneous preterm labor (sPTL) and birth. Amniotic fluid and chorioamniotic membranes (CAM) were collected from women with sPTL who delivered at term (n = 30) or preterm without intra-amniotic inflammation (n = 34), with sterile intra-amniotic inflammation (SIAI, n = 27), or with intra-amniotic infection (IAI, n = 17). Amnion epithelial cells (AEC), Ureaplasma parvum, and Sneathia spp. were also utilized. The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by RT-qPCR and/or immunoassays. AEC co-cultured with Ureaplasma parvum or Sneathia spp. were evaluated for TSLP expression by immunofluorescence and/or RT-qPCR. Our data show that TSLP was elevated in amniotic fluid of women with SIAI or IAI and expressed by the CAM. TSLPR and IL-7Rα had detectable gene and protein expression in the CAM; yet, CRLF2 was specifically elevated with IAI. While TSLP localized to all layers of the CAM and increased with SIAI or IAI, TSLPR and IL-7Rα were minimal and became most apparent with IAI. Co-culture experiments indicated that Ureaplasma parvum and Sneathia spp. differentially upregulated TSLP expression in AEC. Together, these findings indicate that TSLP is a central component of the intra-amniotic host response during sPTL.

Evaluation of two-dimensional ultrasound fetal thymus size in correlation to infection parameters in pregnancies complicated with preterm premature rupture of membranes

Background/aim The thymus is essential for developing the fetal immune system and may show involution upon exposure to acute stress. Early detection of intrauterine infection is urgently needed to avoid fetal affection and sepsis. The present study aims to correlate the fetal thymus size with the infection parameters in pregnancies complicated with preterm premature rupture of membranes (PPROM). Subjects and methods The present study recruited pregnant women who fulfilled the inclusion criteria in a ratio of 1 case to 4 controls according to the study design; Group 1 of twenty cases presenting in PPROM, and Group 2 of eighty cases of women without PPROM. The primary outcome of the study was to measure fetal thymus size by abdominal ultrasound and its correlation with maternal total leukocytic count (TLC) and its differential count, C-reactive protein (CRP), and maternal fever. The secondary outcomes involved the correlation of the fetal thymus size with fetal distress, the occurrence of neonatal infection, Apgar neonatal score, and histological examination of the placenta and membranes for evidence of chorioamnionitis. Results Group 1 had a significantly higher CRP level (P&lt;0.001), higher TLC level (P=0.035), and higher Staff (P&lt;0.001). On the contrary, group 2 had significantly higher AFI (P=0.022), greater Thymus perimeter (P&lt;0.001), and greater thymus transverse diameter (P&lt;0.001). In addition, the pathological examination of the placenta revealed positive signs of infection in group 1 in only 65% of cases. Group 1 had a positive correlation between Thymus perimeter and APGAR score of the neonates (r=0.658, P=0.002), Thymus perimeter and birth weight (r=0.741, P&lt;0.001), Thymus transverse diameter and APGAR score of the neonates (r=0.741, P&lt;0.001), and finally Thymus transverse diameter and birth weight (r=0.734, P&lt;0.001). Group 2 showed a significant positive correlation between the Thymus perimeter and neonatal APGAR score (r=0.232, P=0.039) and Thymus transverse diameter and birth weight (r=0.320, P=0.004). In Group 1, Cases with placental signs of infection (n=13) had higher CRP levels (P=0.046), higher TLC levels (P=0.014), higher Staff (P&lt;0.001), but lower AFI (P=0.032). Conclusion The assessment of the fetal thymus during the routine second- and/or third-trimester scan could be a predictive measure for intra-amniotic infection. However, there is no association between small fetal thymus and adverse perinatal outcomes in uncomplicated pregnancies. Further larger studies with different demographic, maternal characteristics, and different inflammatory processes with and without active management to summarize whether fetal thymus can be used in clinical practice to avoid infection-related fetal morbidities or not.

The Role of Pancreatic Stone Protein (PSP) as a Biomarker of Pregnancy-Related Diseases.

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions.

Research Hotspots and Trends in the Diagnosis of Chorioamnionitis: Based on Bibliometric Analysis from 2010 to 2022.

This study aimed to conduct a bibliometric analysis of literature related to the diagnosis of chorioamnionitis (CAM) and to point out the current research progress, hotspots, and development trends of CAM research. Literature on the diagnosis of CAM from the Web of Science Core Collection (WoSCC) between 2010 and 2022 was retrieved. CiteSpace, VOSviewer, and Online Analysis Platform (OALM) were used to draw maps of authors, articles, journals, institutions, countries/regions, and keywords. A total of 312 articles were included, and the number of articles gradually increased over the study period. The author with the largest number of articles was Roberto Romero. The institution with the largest number of articles was Wayne State University School of Medicine, and the United States was the country that produced the largest number of articles. Analysis of keywords and outbreak words suggested that future research hotspots and trends may focus on early treatment of CAM and more precise, noninvasive, and more sensitive diagnoses. In this study, visualization software and data information mining were innovatively used to conduct a bibliometric analysis of articles in the field of CAM diagnosis, and the current status, hotspots, and development of this field were obtained. Future research hotspots may be the precision diagnosis and treatment of CAM. · There is no bibliometric study on CAM diagnosis in the existing literature.. · The prediction of CAM diagnosis is an important topic to improve maternal and infant prognosis.. · Bibliometrics can effectively guide the direction of future research..

Intra-Amniotic Inflammation or Infection: Suspected and Confirmed Diagnosis of "Triple I" at Term.

Chorioamnionitis (CA) at term of pregnancy can have an infectious and/or inflammatory origin and is associated with adverse outcomes. Triple I (intrauterine inflammation, infection, or both, TI) has been proposed to reduce the overdiagnosis of infection and neonatal overtreatment. The aim of this study is to identify clinical and histological variables that could predict adverse outcomes when TI is suspected and/or confirmed. This retrospective cohort study included 404 pregnancies (gestational age ≥ 37 weeks) that were divided into 5 all-inclusive and mutually exclusive groups. TI was defined according to the NICHD definition of 2015, and it could be confirmed (TI+) or not confirmed (TI-) via histological examination. Signs of infection/inflammation that did not conform to the definition of TI were classified as "clinical suspicion" and could be supported (CS+) or not supported (CS-) by histology. Cases of histological chorioamnionitis (HCA) without clinical manifestation represented a fifth group. Whole placental involvement (WPLI) was defined as a histological inflammation involving the maternal and fetal sides. There were 113 TI+, 30 TI-, 186 CS+, 35 CS-, and 40 isolated HCA cases. WPLI was diagnosed in 133 cases (39.2%). Composite neonatal outcome (CNO) occurred in 114 cases (28.2%) while composite maternal outcome (CMO) occurred in 192 cases (47.5%). Compared with CS+, TI+ was more predictive of CNO (p = 0.001), CMO (p < 0.001), and WPLI (p = 0.005). WPLI was related both to CNO (p < 0.001) and to CMO (p = 0.046). TI+ and WPLI showed similar sensitivity but different specificity in predicting CNO. At logistic regression, CNO was independently predicted by TI+ (OR 2.21; p = 0.001) and by WPLI (OR 2.23; p = 0.001). Compared with CS, TI is a better predictor of CNO and can be useful for the identification of newborns at risk.

Epidemiology and outcomes of respiratory distress in newborns

Respiratory distress of newborns is one of the most frequent causes of infant admission to intensive care units, the development of severe complications of the neonatal period and lethal outcomes.The objective was to study the epidemiology and outcomes of respiratory distress in newborns requiring intensive care measures.Materials and methods. The design was a retrospective observational study. We examined 180 newborns, the mean weight was 1620 (1075–2197.5) g, and the gestational age was 31.8 (29–34.5) weeks. Apgar score at minute 1 was 5 (4–7) and at minute 5 was 7 (6–7) scores. The duration of artificial lung ventilation was 2 (12.5–242) hours, and the duration of treatment in the NICU was 10 (6–19) days. Lethal outcomes occurred in 6 (3%) cases.Results. The most frequent cause of respiratory distress in newborns was respiratory distress syndrome in newborns (53%). The second place was occupied by asphyxia in childbirth (31%). Intra-amniotic infection was detected in 11 (6%) newborns, and intrauterine pneumonia in 5 (3%) infants. Transient tachypnea was registered in 6 (3%) newborns, and meconium aspiration syndrome – in 8 (4%) patients. In premature infants, the most severe course of respiratory distress was noted in pneumonia and asphyxia, in mature infants – in meconium aspiration syndrome. The maximum duration of intensive care measures was observed in intra-amniotic infection – 16 days and respiratory distress syndrome – 11 days. The outcome in 47% was favorable – complete recovery. Unfavorable outcomes included intraventricular hemorrhage (12%), combination of two or more complications (20%), bronchopulmonary dysplasia (5%), and persistent arterial ductus (4%).Conclusion. The outcome of respiratory distress in newborns with adequate assessment of the severity of the condition and timely initiated evidence-based treatment is determined not by the main clinical diagnosis, but by the gestational age and severity of the infant condition at the time of birth.

The role of rhIGF-1/BP3 in the prevention of pulmonary hypertension in bronchopulmonary dysplasia and its underlying mechanism

BackgroundThis study aimed to determine whether postnatal treatment with recombinant human IGF-1 (rhIGF-1)/binding peptide 3 (BP3) ameliorates lung injury and prevents pulmonary hypertension (PH) in bronchopulmonary dysplasia (BPD) models.MethodsWe used two models of BPD in this study: one model that was associated with chorioamnionitis (CA), stimulated by intra-amniotic fluid and exposure to lipopolysaccharide (LPS), whereas the other was exposed to postnatal hyperoxia. Newborn rats were treated with rhIGF-1/BP3 (0.2 mg/Kg/d) or saline via intraperitoneal injection. The study endpoints included the wet/dry weight (W/D) ratio of lung tissues, radial alveolar counts (RACs), vessel density, right ventricular hypertrophy (RVH), lung resistance, and lung compliance. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the degree of lung injury and pulmonary fibrosis. IGF-1 and eNOS expression were detected using western blotting or quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The levels of SP-C, E-cadherin, N-cadherin, FSP1, and Vimentin in the lung tissues were detected by immunofluorescence.ResultsLPS and hyperoxia treatment increased lung injury and pulmonary fibrosis, enhanced RVH and total respiratory resistance, and decreased RAC, pulmonary vascular density and pulmonary compliance in young mice (all p < 0.01). Simultaneously, LPS and hyperoxia induced an increase in epithelial-mesenchymal transition (EMT) in airway epithelial cells. However, rhIGF-1/BP3 treatment reduced lung injury and pulmonary fibrosis, decreased RVH and total respiratory resistance, and enhanced RAC, pulmonary vascular density and pulmonary compliance, as well as inhibited EMT in airway epithelial cells in LPS and hyperoxia treated mice.ConclusionPostnatal rhIGF-1/BP3 treatment relieved the effects of LPS or hyperoxia on lung injury and prevented RVH, providing a promising strategy for the treatment of BPD.

Single versus dual antibiotic regimen in women with term prolonged rupture of membranes and intrapartum fever: a retrospective study.

The impact ofE. coli in causing peripartum infections has been increasing due to rising ampicillin resistance. In this study, we compared maternal and neonatal outcomes of women with prolonged rupture of membranes (ROM >18h) and intrapartum fever, according to two antibiotic regimens they received, and describe the bacterial distribution focusing on risk factors for Enterobacteriaceae-related infectious morbidity. This 10-year retrospective study of women with ROM >18h and intrapartum fever included 62 women who were treated with ampicillin and gentamicin due to suspected intraamniotic infection and 79 without these signs who were treated with ampicillin alone. The primary outcomes were endometritis and neonatal early-onset sepsis (EOS) rates. Outcomes were compared using univariate and multivariate analyses. Among women who received ampicillin alone compared with dual therapy, rates were higher of endometritis (17% vs. 3%, p<0.001), neonatal early onset sepsis (7.5% vs. 0%, p=0.03), Enterobacteriaceae positive placental swab culture (67.9% vs. 15.7%, p<0.001), and histopathological subchorionitis (25.3% vs. 8.0%, p=0.008). Over 83% of Enterobacteriaceae isolates were ampicillin-resistant. Gestational age at delivery >41 weeks, meconium at delivery, ROM >24h and treatment with a single antibiotic agent were associated with the presence of a positive Enterobacteriaceae placental swab culture. Ampicillin compared to dual treatment in women with prolonged ROM and fever might promote the growth of ampicillin-resistant Enterobacteriaceae (including E.coli) and increase risks of maternal and neonatal infectious morbidity.

Clinical chorioamnionitis: where do we stand now?

Intraamniotic infection is an infection resulting in the inflammation of any combination of the amniotic fluid, the placenta, the fetus itself, the fetal membranes, umbilical cord, or the decidua. In the past, an infection of the amnion and chorion or both was dubbed chorioamnionitis. In 2015, a proposal was made by an expert panel that, instead of clinical chorioamnionitis, the name intrauterine inflammation or infection or both be used, abbreviated as Triple I or simply IAI. However, the abbreviation IAI did not gain popularity, and this article uses the term chorioamnionitis. Chorioamnionitis may arise prior to, during, or following labor. It can present as a chronic, subacute, or acute infection. Its clinical presentation is generally referred to as acute chorioamnionitis. The treatment of chorioamnionitis varies widely across the world due to different bacterial causes and the absence of sufficient evidence to support a specific treatment regimen. There are limited randomized controlled trials that have evaluated the superiority of antibiotic regimens for treating amniotic infections during labor. This lack of evidence-based treatment suggests that the current choice of antibiotics is based on limitations in existing research, rather than absolute science. Chorioamnionitis cannot be cured by antibiotic therapy alone without delivery, and therefore it is necessary to make a decision according to the guidelines for induction of labor or acceleration of delivery. When a diagnosis is suspected or established, it is therefore necessary to apply broad-spectrum antibiotics according to the protocol used by each country, and to continue with them until delivery. A commonly recommended first-line treatment for chorioamnionitis is a simple regimen consisting of amoxicillin or ampicillin and once-daily gentamicin. Available information is not sufficient to indicate the best antimicrobial regimen to treat this obstetric condition. However, the evidence that is currently available suggests that patients with clinical chorioamnionitis, primarily women with a gestational age of 34 weeks or more and those in labor, should receive treatment with this regime. However, antibiotic preferences may vary based on local policy, clinician experience and knowledge, bacterial reasons for the infection, antimicrobial resistance patterns, maternal allergies, and drug availability.

Amniotic fluid CD36 in pregnancies complicated by spontaneous preterm delivery: a retrospective cohort study

Objective The aim of this study was to evaluate CD36 concentrations in amniotic fluid in pregnancies complicated by spontaneous delivery with intact fetal membranes (preterm labor, PTL) and preterm prelabor rupture of membranes (PPROM) with respect to the presence of the intra-amniotic infection. Methods A total of 80 women with PPROM and 71 with PTL were included in the study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid CD36 concentrations were assessed by enzyme-linked immunosorbent assay. Microbial colonization of the amniotic cavity (MIAC) was determined by the cultivation and non-cultivation approach. Intra-amniotic inflammation (IAI) was defined as an amniotic fluid bedside interleukin-6 concentration ≥3000 pg/mL. Intra-amniotic infection was characterized by the presence of both MIAC and IAI. Results Women with PPROM with intra-amniotic infection had higher amniotic fluid CD36 concentrations than women without infection (with infection: median 346 pg/mL, IQR 262–384 vs. without infection: median 242 pg/mL, IQR 199–304; p = .006) A positive correlation between amniotic fluid CD36 concentrations and interleukin-6 concentrations was found (rho = 0.48; p < .0001). In PTL pregnancies, no statistically significant difference was found in the amniotic fluid level of CD36 between intra-amniotic infection, sterile IAI, and negative amniotic fluid. Conclusions The presence of intra-amniotic infection is characterized by higher amniotic fluid CD36 concentrations in pregnancies complicated by PPROM. An amniotic fluid CD36 cutoff value of 252.5 pg/mL was found to be optimal for the prediction of intra-amniotic infection. In PTL pregnancies, no statistically significant change in CD36 concentration was found with respect to the presence of intra-amniotic infection.

Multimodal Management of Cervical Insufficiency Complicated by Intra-amniotic Candida albicans Infection.

Bacteria are the most common pathogens implicated in ascending infections in patients with cervical insufficiency. However, Candida albicans is a rare and serious cause of intra-amniotic infection that should be considered on the differential diagnosis. Upon diagnosis following cerclage placement, patients are generally advised to undergo immediate cerclage removal and discontinuation of the pregnancy due to the high risk of maternal and fetal morbidity. However, some patients decline and instead elect to continue the pregnancy with or without treatment. Limited data exist to guide management of these high-risk patients. We describe a case of previable intra-amniotic C. albicans infection diagnosed following physical examination-indicated cerclage placement. The patient declined pregnancy termination and subsequently underwent systemic antifungal therapy as well as serial intra-amniotic fluconazole instillations. Fetal blood sampling confirmed transplacental transfer of maternal systemic antifungal therapy. The fetus delivered preterm and without evidence of fungemia, despite persistently positive amniotic fluid cultures. In a well-counseled patient with culture-proven intra-amniotic C. albicans infection declining termination of pregnancy, multimodal antifungal therapy in the form of systemic and intra-amniotic fluconazole administration may prevent subsequent fetal or neonatal fungemia and improve postnatal outcomes. · Candida is an uncommon cause of intra-amniotic infection in the setting of cervical insufficiency.. · Multimodal antifungal therapy may prevent fetal fungemia related to intra-amniotic Candida infection.. · Fetal blood sampling confirmed transplacental passage of fluconazole after maternal administration..

Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants.

Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. A total of 58 preterm infants born before 34weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.

Maternal and peripartum risk factors for acute funisitis among term deliveries complicated by intraamniotic infection

Acute funisitis (AF), the histologic diagnosis of inflammation within the umbilical cord, represents a fetal inflammatory response and has been associated with adverse neonatal outcomes. There is little known regarding the maternal and intrapartum risk factors associated with the development AF among term deliveries complicated by intraamniotic infection (IAI). To identify maternal and intrapartum risk factors associated with developing AF among term deliveries complicated by IAI. After IRB approval, we conducted a retrospective cohort study of term deliveries affected by clinical IAI at a single tertiary center between 2013-2017 with placental pathology consistent with histologic chorioamnionitis. Exclusion criteria included intrauterine fetal demise, missing delivery information or placental pathology, and documented congenital fetal abnormalities. Maternal sociodemographic, antepartum, and intrapartum factors were compared among patients with AF on pathology to those without AF using bivariate statistics. Regression models developed to estimate adjusted odds ratios (aOR). Of 123 patients meeting inclusion criteria, 75 (61%) had AF on placental pathology. Compared to placental specimens without AF, AF was observed more frequently among patients with maternal body-mass-index (BMI) ≥ 30kg/m2 (58.7% vs, 39.6%, p=0.04) and labor courses with increased rupture of membrane (ROM) duration (17.3 vs, 9.6 hours, p=0.001). Use of fetal scalp electrode (FSE) was observed less frequently in AF (5.3% vs, 16.7%, p=0.04) compared to cases without AF. In regression models, maternal BMI≥30kg/m2 (aOR 2.67, 95% CI 1.21,5.90) and ROM >18 hours (aOR 2.48, 95% CI 1.07,5.75) were significantly associated with AF. FSE use (aOR 0.18, 95% CI 0.04,0.71) was negatively associated with AF. In term deliveries with IAI and histologic chorioamnionitis, maternal BMI≥30kg/m2, and ROM>18 hours were associated with AF on placental pathology. As insight into the clinical impact of AF grows, the ability to predict which pregnancies are at greatest risk for its development may allow for a tailored approach to predicting neonatal risk for sepsis and related comorbidity.

Next-generation sequencing-based detection of Ureaplasma in the gastric fluid of neonates with respiratory distress and chorioamnionitis

Background Respiratory distress is common in neonates admitted to neonatal intensive care units. Additionally, infectious diseases such as intrauterine infections or vertical transmission are important underlying causes of respiratory failure. However, pathogens often cannot be identified in neonates, and there are many cases in which antibacterial drugs are empirically administered. Next-generation sequencing (NGS) is advantageous in that it can detect trace amounts of bacteria that cannot be detected by culturing or bacteria that are difficult to cultivate. However, there are few reports on the diagnosis of infectious diseases using NGS in the neonatal field, especially those targeting respiratory distress. Objective The purpose of our study was to investigate the microorganisms associated with neonatal respiratory distress and to determine whether less invasive collection specimens such as plasma and gastric fluid are useful. Methods Neonates were prospectively recruited between January and August 2020 from Nagoya University Hospital. The inclusion criteria were as follows: 1) admission to the neonatal intensive care unit; 2) respiratory distress presentation within 48 h of birth; and 3) suspected infection, collection of blood culture, and administration of antibiotics. Plasma samples and blood cultures were simultaneously collected. Gastric fluid samples were also collected if the patient was not started on enteral nutrition. Information on the patients and their mothers were collected from the medical records. DNA was extracted from 140 µL of plasma and gastric fluid samples. DNA sequencing libraries were prepared, and their quality was analyzed. DNA libraries were sequenced using high-throughput NGS. The NGS data of plasma and gastric fluid samples were analyzed using the metagenomic pipeline PATHDET, which calculated the number of reads assigned to microorganisms and their relative abundance. Putative pathogens were listed. Results Overall, 30 plasma samples and 25 gastric fluid samples from 30 neonates were analyzed. Microorganism-derived reads of gastric fluid samples were significantly higher than those of plasma samples. Transient tachypnea of the newborn was the most common cause of respiratory distress with 13 cases (43%), followed by respiratory distress syndrome with 7 cases (23%). There were 8 cases (29%) of chorioamnionitis and 7 cases (25%) of funisitis pathologically diagnosed. All blood cultures were negative, and only two gastric fluid cultures were positive for group B Streptococcus (Patient 15) and Candida albicans (Patient 24). Putative pathogens that met the positive criteria for PATHET were detected in four gastric fluid samples, one of which was group B Streptococcus from Patient 15. In the gastric fluid sample of Patient 24, Candida albicans were detected by NGS but did not meet the positive criteria for PATHDET. Cluster analysis of the plasma samples divided them into two study groups, and the indicator genera of each cluster (Phormidium or Toxoplasma) are shown in Figure 1. Clinical findings did not show any significant differences between the two groups. Cluster analysis of the gastric fluid samples divided them into three study groups, and the indicator genera of each cluster (Ureaplasma, Nostoc, and Streptococcus) are shown in Figure 2. The incidence rate of chorioamnionitis was significantly higher in Ureaplasma group than in the other two groups. Conclusion Gastric fluid may be useful for assessing neonatal patients with respiratory distress. To the best of our knowledge, this was the first study to reveal that the presence of Ureaplasma in the gastric fluid of neonates with respiratory distress was associated with chorioamnionitis. The early diagnosis of intra-amniotic infections using gastric fluid and its treatment may change the treatment strategy for neonatal respiratory distress. Screening for Ureaplasma in neonates with respiratory distress may reduce the need for empirical antibiotic administration. Further research is required to confirm these findings.

Maternal Morbidity Rates Relative to Length of Labor in a Multiethnic Patient Population [ID: 1337798

INTRODUCTION: Prolonged induction of labor is associated with increased morbid maternal outcomes. Induction of labor length varies by institution and labor management. The objective of this study was to determine the risk of morbid outcomes increasing hours of labor induction in a multiethnic tertiary care center. METHODS: We conducted a retrospective cohort study on patients undergoing scheduled induction of labor from June 2020 to May 2021 at a tertiary care center. Nulliparous singleton term pregnancies with intact membranes who had an initial cervical dilation less than 3 were included. Length of labor induction was defined as first intervention to birth. Morbid outcomes included suspected intraamniotic infection (IAI), postpartum hemorrhage (PPH), and cesarean birth. Multivariable logistic regressions were performed relative to the length of labor. RESULTS: Two hundred sixty-seven patients were included in our study, with 18.0% Asian American/Pacific Islander, 6.4% Black/non-Hispanic, 20.2% Hispanic, 32.6% White/non-Hispanic, 17.6% multiracial/other, and 5.2% unknown. The median labor length was 28.5 hours (interquartile range 21.2–38.5). The rates of IAI was 22%, PPH 12%, and cesarean birth 22%. For every hour of labor, there was 1.04 increased odds of IAI, 1.08 odds of cesarean birth, and 1.05 odds of PPH after adjusting for confounders (P&lt;.01). When comparing White versus non-White patients, there were no differences in labor length (28.4 hours versus 28.6 hours, P=.46) and no differences in IAI, PPH, and cesarean. CONCLUSION: For each hour of labor, the risk of IAI, PPH, and cesarean birth increased by 4%, 8%, and 5%, respectively. Characteristics contributing to this association may be multifactorial and suggest labor management should aim for an expedient birth.

Defined Protocol Including Quantitative Blood Loss Obviates the Need for Postpartum Day 1 Complete Blood Count in Uncomplicated Vaginal Deliveries [ID: 1371414

INTRODUCTION: A postpartum day 1 (PPD1) complete blood count (CBC) is a common postpartum practice. The purpose of PPD1 CBCs is to identify patients with anemia that may benefit from a blood transfusion (BT). However, after the introduction of quantitative blood loss (QBL), we questioned the benefit of PPD1 CBC collection. This study aimed to determine whether PPD1 CBCs provided clinical utility in objectively defined uncomplicated vaginal deliveries. METHODS: A retrospective chart review was performed on all vaginal deliveries from January 1, 2021 to January 31, 2022, at a single-site level IV maternity facility. Exclusion criteria were as follows: intraamniotic infections, QBL of 1,000 mL or more, starting hematocrit less than 35, or no documented QBL. Patients were divided into three groups based on QBL: less than 500 mL, 501–749 mL, and 750–999 mL. RESULTS: The total number of deliveries was 2,427. One thousand two hundred fifty-three met inclusion criteria: QBL less than 500 mL: 922; 501–749 mL: 240; and QBL 750–999 mL: 91. Among all included deliveries, one patient, in the QBL 750- to 999-mL group, received a BT due to symptomatic anemia but had hemoglobin and hematocrit greater than 7/21. The total cost of PPD1 CBCs for included deliveries was $87,710. CONCLUSION: None of the patients in this study who met the inclusion criteria received a BT based on the PPD1 CBC result. This indicates that a PPD1 CBC is of limited clinical utility when uncomplicated vaginal deliveries are defined using this purely objective protocol in the setting of QBL. Therefore, elimination of a PPD1 CBC is consistent with best practice and results in postpartum care cost reduction.