Clinical Chorioamnionitis Research Articles

The Impact of Prenatal Diagnosis and Treatment on Early Neonatal Problems

OBJECTIVE: Obstetric problems have detrimental effects on both pregnancy and newborn. We aimed to examine the relationship between pregnancy complications and newborn morbidities. STUDY DESIGN: The newborns admitted to the neonatal intensive care unit between September 2019 and August 2022 were included in this retrospective cross-sectional study. Antenatal morbidities and neonatal complications including low APGAR-score (<5), bronchopulmonary dysplasia, early neonatal sepsis, and early neonatal death were evaluated. Pearson-χ2 cross-tabs were used to compare two variables. A p-value <0.05 was determined statistically significant. RESULTS: Among the 686 infants analyzed, 94 (13.7%) had early neonatal death, 264 (38.5%) had bronchopulmonary dysplasia, 259 (37.8%) had early neonatal sepsis, and 424 (61.9%) had feeding intolerance. Early neonatal sepsis was observed significantly higher in newborns whose mothers had urinary tract infection in the last two weeks (p<0.001), preterm premature rupture of membranes (p=0.006), or clinical chorioamnionitis (p<0.001). Early neonatal death was found significantly higher in pregnancies with preeclampsia (p<0.001), preterm premature rupture of membranes (p<0.001), clinical chorioamnionitis (p<0.001), or small-for-gestational-age (p<0.001). Preeclampsia and magnesium neuroprophylaxis were found significantly higher in neonates with feeding intolerance (p<0.001). Backward: LR logistic regression analysis based on early neonatal sepsis risk revealed that birth week, preterm premature rupture of membranes, clinical chorioamnionitis, small-for-gestational-age, and urinary tract infection were significant parameters affecting the risk of early neonatal sepsis (p<0.05). CONCLUSION: Preventing premature births and cautious management of pregnancy complications may be helpful in reducing adverse neonatal outcomes. Early detection of high-risk pregnancies and transfer to a tertiary center may be helpful to improve neonatal outcomes.

Two- and Three-Dimensional Ultrasonographic Evaluation of the Fetal Thymus in Women with Preterm PrematureRupture of Membranes: A Prospective Study

Objective: To evaluate the relationship between fetal thymus diameter and perinatal outcomes in preterm premature rupture of membranes (PPROM) cases and to compare three-dimensional (3D) fetal thymus volume in the same cases. Material and Methods: This was a prospective study from March 2019 through March 2020. Women diagnosed with PPROM between 24 and 33+6 weeks of gestation were included. Pregnancies were divided into 2 groups as small and normal according to the thymus size nomogram. The virtual organ computeraided analysis software calculated the volumes automatically. Results: In 41 patients, measurements could be successfully acquired with twodimensional and 3D sonography. Twenty eight (68.3%) patients were in the small thymus group and 13 patients (31.7%) were in the normal thymus group. The probability of clinical chorioamnionitis increased 7.7-fold-times in cases with small thymus (odds ratio 7.7, 95% confidence interval 1.1-67.4, p=0.038). The latency period was significantly higher in the normal thymus group. The correlation between transverse diameter and thymus volume was analyzed according to gestational age at ultrasound measurement and a significant correlation was observed between them. Conclusion: A small transverse diameter of the thymus in PPROM cases may be associated with clinical chorioamnionitis, and a normal thymus diameter may predict a longer latency period. In addition, although transverse thymus diameter was correlated with thymus volume, no significant volume difference was observed between the groups when percentile classification was made.

The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study.

This study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients. We prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture. A total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant. The N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.

Risks of microbial colonization in newborn born to mothers with chorioamnionitis

BACKGROUND: Chorioamnionitis, or intra-amniotic infection, is an infection of the membranes and amniotic cavity caused by polymicrobial associations, including Streptococcus agalactiae (SGB), predominantly localised to the lower genital tract of women. The colonization of a infant with GBS occurs as a result of ascending infection from the mother, in the intranatal period during passage through the natural birth canal of the mother. Colonization of the skin and mucous membranes of the infant in the vast majority of cases proceeds without the clinical implementation of the infectious process, only 2-5% of infected newborns develop an infection associated with GBS.
 AIM: The aim of the study is to investigate the vaginal and uterine microflora in women with chorioamnionitis and to determine the degree of neonatal colonization.
 MATERIALS AND METHODS: A microbiological examination was undertaken in 113 motherchild pairs. Main group (group I): pregnant women with full-term pregnancy (37 weeks gestation) who were diagnosed with clinical chorioamnionitis and prescribed antibacterial agents, and their newborns (n = 77). Comparison group (group II): 36 pregnant women without clinical chorioamnionitis with a gestational age of 37 weeks gestation and their newborns with a physiological course of the early neonatal period. Clinical specimens: secretions from the posterior vaginal fornix and the inner surface of the uterine wall at surgical delivery in women in labour with clinical signs of chorioamnionitis (group I) and without clinical manifestations of chorioamnionitis (group II). Material was obtained at the height of body temperature in group I and during the 1st period of labour in group II. The clinical materials were umbilical cord blood, skin surface of the occipital fold, discharge from the cavity, and discharge from the tracheobronchial tree (in case of respiratory therapy with ventilator therapy).
 RESULTS: At bacteriological examination in women of Group I the frequency of microorganism isolation from the vaginal discharge was: Enterococcus faecalis 31.8%, S. agalactiae (SGB) 30.3% and Escherichia coli 24.2%. The proportion of SGB at 106 CFU/ml was 70%. The proportion of E. coli at 106 CFU/ml was 75% and that of Candida albicans 72%. Among microorganisms isolated from the uterine cavity, the proportion of SGB at 106 CFU/ml was 60%, E. coli 100%. Bacteriological testing of the examined children showed that S. agalactiae (SGB), E. faecalis and E. coli were isolated from almost all neonatal loci studied. Comparative studies have shown that the colonisation of newborn infants was most frequently caused by S. agalactiae (SGB), E. faecalis and E. coli. The frequency of maternal transmission of these organisms to the foetus and the newborn is 100% for S. agalactiae (SGB) and 1850% for E. faecalis and E. coli. In all examined children of the main group and with the presence of S. agalactiae (SGB) in the uterine cavity of their mothers (n = 5), these microorganisms were isolated from different loci (in all cases from the skin surface of the auricular fold and from oral discharge, and in three cases from umbilical cord blood), but clinical manifestations of the infection process did not develop in any child.
 CONCLUSIONS: Despite antibiotic therapy for chorioamnionitis in women, the incidence of micro-organism isolation from both the vagina and the uterine cavity remains high. In most cases, newborns from mothers with chorioamnionitis colonised with micro-organisms, including S. agalactiae (SGB), do not develop a clinical picture of an infective process. Further research is needed to develop preventive measures in terms of perinatal and neonatal infections.

Effect of clinical chorioamnionitis on breathing effort in premature infants at birth: a retrospective case–control study

RationaleAntenatal inflammation, usually associated with chorioamnionitis, is a major cause of premature birth. As inflammation could depress respiratory drive, we have examined the effect of clinical chorioamnionitis (CCA) on spontaneous...

Assessment of labor progress by ultrasound vs manual examination: a randomized controlled trial

Assessment of labor progress via digital examination is considered the standard of care in most delivery rooms. However, this method can be stressful, painful, and imprecise, and multiple examinations increase the risk for chorioamnionitis. Intrapartum ultrasound was found to be an objective, noninvasive tool to monitor labor progression. This study aimed to investigate whether, among nulliparous women, the use of intrapartum ultrasound can reduce the rate of intrapartum fever by reducing the number of digital examinations. This was a prospective, randomized controlled trial in term nulliparas admitted with prelabor rupture of membranes, induction of labor, or in latent phase of labor with a cervical dilation of <4 cm. Women were randomized into 1 of the following 2 arms: (1) labor progress assessed by ultrasound, avoiding digital examinations as much as possible; and (2) control group in which labor progression was assessed according to the regular protocol. Before the study, all labor ward physicians underwent training in intrapartum ultrasound. A total of 90 women were randomized to the ultrasound group and 92 were randomized to the control group. When compared with the control group, the ultrasound group had significantly lower rates of intrapartum fever (11.1% vs 26.1%; P=.01), clinical chorioamnionitis (3.3% vs 16.5%; P>.01), and histologic chorioamnionitis (2.2% vs 9.8%; P=.03). The median number of digital examinations was significantly lower in the ultrasound group (5; interquartile range, 4-6) than in the control group (8; interquartile range, 6-10; P<.01). The median number of digital examinations per hour in the ultrasound group was significantly lower than in the control group (0.2 vs 0.4; P<.01). The induction rates, time from admission to delivery, mode of delivery, Apgar score at 5 minutes, and neonatal intensive care unit admission rates did not differ significantly between the groups. The use of intrapartum ultrasound lessens the total number of digital examinations needed to be performed during labor and, consequently, the incidence of intrapartum fever and chorioamnionitis are reduced. No adverse effects on labor progression and short-term maternal or neonatal outcomes were noted.

Blood neutrophil-to-lymphocyte ratio as a risk factor in treatment for retinopathy of prematurity.

To investigate the blood neutrophil-to-lymphocyte ratio (NLR) as a risk factor for retinopathy of prematurity (ROP) development or treatment. Retrospective cohort study. Infants who underwent ROP screening at Shiga University of Medical Science Hospital and Omihachiman Community Medical Center between April 2010 and December 2021 were included in this study. Screening criteria were gestational age (GA) < 32weeks or birth weight (BW) < 1500g. Multivariate logistic regression analysis was applied to investigate whether the NLR constituted an independent risk factor for ROP development or treatment. The objective variable was ROP development or treatment, and the explanatory variables were GA, BW, NLR, maternal infection or clinical chorioamnionitis and corticosteroid use by the mother. Maternal infection or clinical chorioamnionitis and corticosteroid use by the mother was included in the explanatory variables to adjust for factors affecting the NLR. In total, 220 infants met the inclusion criteria, of whom 125 developed ROP, whereas 95 infants did not display ROP. GA was significantly associated with ROP development (odds ratio (OR): 0.41, p < 0.001); however, the NLR was not significantly associated with ROP development (OR: 1.0, p = 0.74). Thirty-eight infants received treatment for ROP, whereas 182 infants had no such treatment. BW and the NLR were significantly associated with ROP treatment (OR: 1.6 and 0.66, p < 0.001 and 0.003, respectively). The NLR was not a risk factor for ROP development but was a risk factor for ROP treatment.

Evaluation of a clinical protocol for the management of fever in labor among pregnant women at term: A quality-improvement study.

To assess the impact of a quality-improvement initiative designed to increase diagnostic accuracy and adequate management of clinical chorioamnionitis (CC) at a tertiary center. Chorioamnionitis occurs in 1%-13% of term pregnancies and increases maternal and neonatal peripartum complications; often over-diagnosed, it leads to unnecessary investigations and treatments. This was an interrupted time-series study. In September 2017 two interventions were implemented: (1) staff training and (2) standardized clinical protocol for the management of fever in labor. All singleton term pregnancies were included. CC cases were reviewed in the pre-intervention (2015-2016, n= 179) and post-intervention (2017-2018, n= 142) groups. CC criteria based on the American College of Obstetricians and Gynecologists guidelines, antibiotics, maternal and neonatal outcomes, and pathology were compared. A cost-consequence analysis was performed. Incidence of CC decreased from 8.2 to 5.6 per 10 person-year (P< 0.001). This was associated with a significant increase in diagnostic accuracy from 15.7% to 73.2% (P< 0.001). Weight-adjusted tobramycin dosage improved from 8.8% to 69.1% (P< 0.001). Maternal length of hospitalization and readmissions decreased significantly, without affecting neonatal sepsis rate. Interventions decreased yearly hospital costs associated with CC by 23.4%. Standardizing the management of fever in labor significantly increased the diagnostic accuracy of CC and decreased the misuse of antibiotics in term pregnancies. CC costs decreased by 23.4%.

Microbiological features and perinatal outcomes in patients with preterm premature rupture of membranes and oligohydramnios

BACKGROUND: Oligohydramnios in preterm premature rupture of membranes is the cause of increased perinatal morbidity and mortality among preterm newborns. Microbiological features in women with preterm premature rupture of membranes and oligohydramnios are probably some of the determining factors affecting the implementation of an unfavorable outcome of gestation.&#x0D; AIM: The aim of this study was to determine microbiological features and perinatal outcomes in patients with preterm premature rupture of membranes and oligohydramnios.&#x0D; MATERIALS AND METHODS: This retrospective study conducted from 2018 to 2021 included 161 pregnant women with PPROM at 24 to 33 weeks and 6 days of gestation. Of these, the main group consisted of 83 patients with signs of oligohydramnios, while the control group comprised 78 patients without oligohydramnios. Patient examination upon admission to the hospital included analysis of the amniotic fluid index, the white blood cell differential, plasma ferritin and C-reactive protein levels, and bacteriological tests of vaginal secretions by isolating and growing microbes on optimal culture media.&#x0D; RESULTS: The patients with oligohydramnios had shorter latent period (р = 0.004), but the noted distinctions were a higher frequency of clinical chorioamnionitis (р = 0.025), fetal distress (р = 0.030), and earlier parturition (р = 0.040) with more frequent caesarean sections (р = 0.016) compared to the control group. Vaginal microbiota in the main group showed a higher prevalence of Staphylococcus aureus (р = 0.008), Bacteroides spp. (р = 0.030), Streptococcus spp. (р = 0.002), Micrococcus spp. (p 0.001), Bacillus subtilis (p 0.001), Bacillus megaterium (p = 0.009), Bacillus buchneri (р = 0.008), Klebsiella pneumoniae (р = 0.002), Haemophilus spp. (р = 0.005) and no Candida albicans compared to the control group. In the main group, newborns more often had a lower body weight at birth (р = 0.002) and a lower Apgar score at the fifth minute (р = 0.011). They also showed higher incidences of respiratory distress syndrome (р = 0.006), bronchopulmonary dysplasia (р = 0.036), congenital pneumonia (р = 0.011) and necrotizing enterocolitis (р = 0.022) and more often needed treatment in an intensive care unit (р = 0.034), including surfactant supplementation (р = 0.007), cardiotonic support (р = 0.004) and artificial lung ventilation (р = 0.006) compared to the control group.&#x0D; CONCLUSIONS: Oligohydramnios in preterm premature rupture of membranes is associated with pronounced dysbiotic changes in the vaginal microbiota including the prevalence of Micrococcus spp., Streptococcus spp., Staphylococcus aureus and absence of Candida spp. from the isolates, as well as increased incidence of adverse perinatal outcomes.

Pregnancy outcomes following early fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome at 16 weeks’ gestation

Ample evidence supports fetoscopic laser photocoagulation of placental anastomoses as a first-line treatment for twin-to-twin transfusion syndrome, but little is known about the outcomes following procedures conducted in the early second trimester. This study aimed to evaluate perinatal outcomes following early fetoscopic laser placental photocoagulation performed for twin-to-twin transfusion syndrome at 16 weeks' gestation. This retrospective review included monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome necessitating fetoscopic laser photocoagulation at a single tertiary center from 2012 to 2021. The 2 cohorts were defined as cases undergoing laser surgery at 16+0/7 to 16+6/7 weeks' gestation (early laser group) and those undergoing laser surgery ≥17 weeks' gestation (standard laser group), respectively. Primary outcomes included rates of immediate chorioamniotic membrane separation, preterm premature rupture of membranes, and clinical chorioamnionitis. Secondary outcomes included twin survival rates at birth and 30 days of life. Outcomes were compared between cohorts with a P value of <.05 denoting statistical significance. A total of 343 cases were included (35 early laser participants and 308 standard laser participants). The early laser group typically had higher Quintero staging at the time of the procedure. Following intervention, the early laser group had significantly higher rates of chorioamniotic separation than the standard laser group (34.3% vs 1.3% of cases; P<.001) and higher rates of preterm prelabor rupture of membranes (45.7% vs 25.0%; P=.009) and chorioamnionitis (11.4% vs 1.3%; P=.005). Even after adjustment for higher Quintero staging in the early laser group, twin survival was not significantly different between study groups. Early laser surgery for twin-to-twin transfusion syndrome performed at 16 weeks' gestation is associated with significantly higher rates of chorioamniotic separation, preterm rupture of membranes, and chorioamnionitis. However, twin survival does not seem to be negatively impacted following early laser surgery.

Effect of gestational age at first delivery and interpregnancy interval on the recurrence of clinical chorioamnionitis

BACKGROUNDThere is an increased odds of having a recurrence of clinical chorioamnionitis in patients with a diagnosis of clinical chorioamnionitis compared with those without clinical chorioamnionitis in a previous pregnancy. However, it is unclear how gestational age at delivery of the first pregnancy or interpregnancy interval may contribute to this increased risk.OBJECTIVEThis study aimed to evaluate how gestational age of delivery in a first pregnancy and interpregnancy interval affect the odds of recurrent clinical chorioamnionitis.STUDY DESIGNUsing maternally linked birth record files, Nulliparous patients from California with at least 2 consecutive deliveries between the gestational ages of 20 and 44 weeks from 2007 to 2012 were identified. The rates of clinical chorioamnionitis in the second pregnancy for patients with clinical chorioamnionitis vs those without clinical chorioamnionitis in the first pregnancy, stratified by the gestational age at delivery of the first pregnancy were determined. As a secondary analysis, the analysis by interpregnancy interval (<18 months vs ≥18 months) was stratified. Corresponding crude and adjusted odds ratios for each stratum were calculated to assess the association of clinical chorioamnionitis in the first and second pregnancies.RESULTSAmong 31,571 nulliparous patients with clinical chorioamnionitis in the first pregnancy, the frequency of clinical chorioamnionitis in the next pregnancy was 4.0% (1257 cases). This was in comparison with the 1.0% (9177 of 896,154) of nulliparous patients without clinical chorioamnionitis in the first pregnancy who were diagnosed with clinical chorioamnionitis in the next pregnancy (adjusted odds ratio, 2.78; 95% confidence interval, 2.61–2.96). The absolute frequency of recurrence was the highest (54 cases [8.2%]) in those who delivered at 20 to 24 weeks of gestation in the first pregnancy with the diagnosis of clinical chorioamnionitis (adjusted odds ratio, 1.76; 95% confidence interval, 1.25–2.48). For pregnancies delivered at term in the first pregnancy, the frequency of clinical chorioamnionitis in the next pregnancy was higher in those diagnosed with clinical chorioamnionitis in the first pregnancy than in those without clinical chorioamnionitis in the first pregnancy (4.0% vs 1.0%; adjusted odds ratio, 2.85; 95% confidence interval, 2.66–3.05). An interpregnancy interval of <18 months was not associated with increased odds of recurrent clinical chorioamnionitis.CONCLUSIONThe odds of recurrence of clinical chorioamnionitis were the strongest when a patient delivered in the term to postterm period in the first pregnancy, with the absolute risk being the highest when the first pregnancy was delivered in the periviable period (20–24 weeks of gestation). The interpregnancy interval did not seem to modify the risk of recurrent clinical chorioamnionitis.

A nationwide study of obstetric management and outcomes in premature rupture of membrane at term: Report from the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2017-2018.

This nationwide study aimed to investigate the practical management of term premature rupture of membrane (PROM) and its relationship with maternal and neonatal outcomes. We conducted a questionnaire survey of 415 facilities participating in the Japan Perinatal Registry Network of the Japan Society of Obstetrics and Gynecology in 2016. The patients were women expecting vaginal birth after PROM at term without clinical chorioamnionitis. We classified the facilities into three groups based on duration of the expectant management after PROM (within 24, 24, and 48 h). Furthermore, we analyzed the association between perinatal outcomes and management protocol using the Japan Perinatal Registry Network Database 2016. Of 415 facilities, 346 (83.4%) completed and returned the survey. Among 231 facilities with management protocols, an interval of 3 days from PROM to delivery was acceptable in 167 facilities (72.3%). One hundred forty-nine facilities (64.5%) responded that they did not perform mechanical cervical dilation, and 90 (39.0%) used oxytocin as a uterotonic irrespective of cervical maturation. The number of hospitals that had a policy to administer antibiotics to Group B streptococcus-positive patients was 211 (91.3%). Neonatal outcomes at birth and the frequency of cesarean section and postpartum fever did not differ among the three groups. Most facilities in the Japan Perinatal Registry Network managed women at term to delivery within 3 days after PROM with attention to bacterial infection. Expectant management up to 48 h after PROM did not increase the risk of postpartum fever, compared to labor induction immediately after PROM.

Association of clinical signs of chorioamnionitis with histological chorioamnionitis and neonatal outcomes

Background Chorioamnionitis is a risk factor for fetal and neonatal outcomes. Therefore, predicting histological chorioamnionitis (HCA) and neonatal outcomes using clinical parameters could be helpful in management and preventing morbidities. Objective To determine if parameters of clinical chorioamnionitis (CCA) would be associated with HCA and neonatal outcomes. Study design In this cohort study using a retrospective design, we analyzed the performance of signs of CCA in predicting HCA, and neonatal outcomes. Data were extracted from the electronic health record for all neonates with documented CCA delivered at our institution from 2011 to 2016. We compared our findings based on the old ACOG definition of CCA and the new definition released in 2017 – maternal fever plus any of fetal tachycardia, maternal leukocytosis, and purulent vaginal discharge. Maternal tachycardia and uterine tenderness were removed from the new criteria. Neonatal laboratory samples on admission, 12 h and 24 h were used to define the three time points of neonatal suspected sepsis. Results There were 530 mothers-infant dyads with chorioamnionitis. Seventy-three were preterm, and 457 were term. Eighty-eight percent of the preterm mothers had CCA, and HCA was present in 62.5% of 72 preterm placentas. Preterm infants with placental HCA significantly had lower birth weight, gestational age, placental weight, and more infants with lower 5-minute Apgar scores, compared to those with no HCA. In preterm infants, maternal urinary tract infection was significantly associated with decreased odds for HCA (OR 0.22, CI 0.10 − 0.71). More preterm babies with suspected sepsis criteria at the 3 time points had HCA (all p ≤ .01). In the term cohort, 95.4% and 65.6% had CCA and HCA, respectively. In term infants (n = 457), maternal leukocytosis (p = .002) and prolonged rupture of membranes (PROM; p = 002) were associated with HCA. Suspected sepsis was associated with PROM (p = .04), HCA (p = .0001), and maternal leukocytosis (p ≤ .05) in at least 1 of the 3 time points. Conclusion Though maternal leukocytosis was significantly associated with the presence of HCA in the term cohort, there were no CCA criteria that accurately predicted presence of HCA in either the preterm or the term infants.

Optimal timing of labor induction after prelabor rupture of membranes at term: a secondary analysis of the TERMPROM study

In the case of prelabor rupture of membranes at term, the risk for neonatal and maternal infectious morbidity increases progressively with time from prelabor rupture of membranes. Although most studies identified a benefit associated with early induction within the first 24 hours following term prelabor rupture of membranes, there is currently no precise data regarding how early should induction be scheduled. This study aimed to identify the optimal timing of labor induction among women with term prelabor rupture of membranes by comparing the maternal and neonatal outcomes associated with labor induction with those of expectant management at any given 1-hour interval following prelabor rupture of membranes. This was a secondary analysis of data from the TERMPROM trial, an international, multicenter, randomized clinical trial on immediate delivery vs expectant management of women with prelaor rupture of membranes at term (≥37+0/7 weeks' gestation). We considered all participants as a single cohort of women with term prelabor rupture of membranes, irrespective of the original randomized study group allocation. For each given 1-hour time interval within the first 36 hours following prelabor rupture of membranes, we compared the outcomes of subjects for whom labor induction was initiated during this interval with those of subjects managed expectantly at the same time interval. The primary neonatal outcome was a composite of neonatal infection and admission to the neonatal intensive care unit. The primary maternal outcomes included maternal infection (clinical chorioamnionitis or postpartum fever) and cesarean delivery. Of the 4742 subjects who met the study criteria, 2622 underwent labor induction, and 2120 experienced a spontaneous onset of labor. The rates of the neonatal composite outcome, neonatal admission to intensive care unit, and maternal infection increased progressively with time after prelabor rupture of membranes. The risk for these outcomes was lower among women who underwent induction when compared with those managed expectantly within the first 15 to 20 hours after prelabor rupture of membranes without affecting the risk for cesarean delivery. In addition, women who underwent labor induction within the first 30 to 36 hours had a shorter prelabor rupture of membranes to delivery time and a shorter total maternal hospital stay when compared with those managed expectantly at the same time interval. Among women managed expectantly, less than two-thirds (64%; 1365/2120) experienced a spontaneous onset of labor within the first 24 hours following prelabor rupture of membranes. These findings suggest that immediate labor induction seems to be the optimal management strategy to minimize neonatal and maternal morbidity in the setting of prelabor rupture of membranes at term gestations. In cases for which immediate induction is not feasible, labor induction remains the preferred option over expectant management if performed within the first 15 to 20 hours after prelabor rupture of membranes.

Evaluation of the effectiveness of Ampicillin and Lactobacillus casei rhamnosus treatment in cases of preterm premature rupture of membranes remote from term.

Preterm premature rupture of membranes (PPROM) remote from term is an important obstetric cause of maternal and fetal adverse outcomes. The aim of our study is to examine the efficacy of ampicillin and Lactobacillus casei rhamnosus treatment in cases of PPROM remote from term. The study was carried out by examining the results of cases who were given Ampicillin and Lactobacillus casei rhamnosus treatment. The patients were divided into two groups. Group 1 who didn't develop clinical chorioamnionitis and Group 2 who developed clinical chorioamnionitis. Obstetric characteristics, neonatal outcomes, adverse events were recorded. A total of 46 pregnant women, 40 in Group 1 and six in Group 2, were included in the study. The frequency of clinical chorioamnionitis developing during the treatment was found to be 13.0%. Mean gestational age at diagnosis was 28.43 ± 2.38 and 28.17 ± 1.33 for Groups 1 and Group 2, respectively. Mean gestational age at the time of delivery was 32.38 ± 2.07 31.33 ± 1.63 for Group 1 and Group 2, respectively. The mean latency period for Group 1 and Group 2 was 27.45 ± 1.71 days, 23.66 ± 4.53, respectively. Sepsis developed in six newborns (15%) in Group 1, while it developed in three newborns (50%) in Group 2. While 90% of the babies in Group 1 were discharged from the hospital, this rate was 66.7% in Group 2. Ampicillin + Lactobacillus casei rhamnosus is an effective treatment method in PPROM cases and positively affects perinatal outcomes.

Secretory phospholipase A2 expression and activity in preterm clinical chorioamnionitis with fetal involvement.

Secretory phospholipase A2 (sPLA2) regulates the first step of inflammatory cascade and is involved in several pathological processes. sPLA2 also plays a role in preterm labor and parturition, since they are triggered by inflammatory mediators such as prostaglandins. Interestingly, chorioamnionitis (i.e., the presence of intrauterine inflammation) is also often associated with preterm birth. We aimed to verify if chorioamnionitis with fetal involvement modifies sPLA2 activity and expression profile in mothers and neonates delivered prematurely. We collected maternal plasma and amniotic fluid, as well as bronchoalveolar lavage fluid from preterm neonates born to mothers with or without clinical chorioamnionitis with fetal involvement. We measured concentrations of sPLA2 subtype-IIA and -IB, total enzyme activity, and proteins. Urea ratio was used to obtain epithelial lining fluid concentrations. Enzyme activity measured in maternal plasma (P < 0.001) and amniotic fluid (P < 0.001) was higher in chorioamnionitis cases than in controls. This was mainly due to the increased production of sPLA2-IIA, as the subtype -IB was present in a smaller amount and was similar between the two groups; sPLA2-IIA was increased in epithelial lining fluid (P = 0.045) or increased, although without statistical significance, in maternal plasma (P = 0.06) and amniotic fluid (P = 0.08) of chorioamnionitis cases. Cytokines that are known to increase sPLA2-IIA expression (TNF-α and IL-1β) or whose expression was increased by sPLA2-IIA (IL-8) were higher in histologically confirmed chorioamnionitis [TNF-α (P = 0.028), IL-1β (P < 0.001), and IL-8 (P = 0.038)]. These data represent the basis for future studies on sPLA2-IIA inhibition to prevent deleterious consequences of chorioamnionitis and preterm birth.

Maternal plasma cytokines and the subsequent risk of uterine atony and postpartum hemorrhage.

To determine whether the maternal plasma concentrations of cytokines are higher in pregnant women with postpartum hemorrhage (PPH) compared to pregnant women without PPH. A retrospective case-control study included 36 women with PPH and 72 matched controls. Cases and controls were matched for gestational age at delivery, labor status, delivery route, parity, and year of sample collection. Maternal plasma samples were collected up to 3days prior to delivery. Comparison of the plasma concentrations of 29 cytokines was performed by using linear mixed-effects models and included adjustment for covariates and multiple testing. A false discovery rate adjusted p-value <0.1 was used to infer significance. Random forest models with evaluation by leave-one-out and 9-fold cross-validation were used to assess the combined value of the proteins in predicting PPH. Concentrations of interleukin (IL)-16, IL-6, IL-12/IL-23p40, monocyte chemotactic protein 1 (MCP-1), and IL-1β were significantly higher in PPH than in the control group. This difference remained significant after adjustment for maternal age, clinical chorioamnionitis, and preeclampsia. Multi-protein random forest proteomics models had moderate cross-validated accuracy for prediction of PPH [area under the ROC curve, 0.69 (0.58-0.81) by leave-one-out cross validation and 0.73 (0.65-0.81) by 9-fold cross-validation], and the inclusion of clinical and demographic information did not increase the prediction performance. Pregnant women with severe PPH had higher median maternal plasma concentrations of IL-16, IL-6, IL-12/IL-23p40, MCP-1, and IL-1β than patients without PPH. These cytokines could serve as biomarkers or their pathways may be therapeutic targets.

Placental clearance not synthesis tempers exaggerated pro-inflammatory cytokine response in neonates exposed to chorioamnionitis.

The source and clearance of cytokines in the fetal circulation in term pregnancies complicated by chorioamnionitis remains unclear as are the contributions of placental transport, synthesis, and clearance. The objectives of the study were to determine (1) fetal and/or placental contributions to synthesis and/or clearance of inflammatory and anti-inflammatory cytokines in term pregnancies complicated by chorioamnionitis and (2) whether this differs in pregnancies further complicated by fetal hypoxia. Prospective cohort study of pregnancies >37 weeks gestational age that included: Group 1, uncomplicated cesarean delivery without labor (n = 20); Group 2, uncomplicated vaginal delivery (n = 30); Group 3, pregnancies complicated by chorioamnionitis (n = 10); Group 4, complicated by chorioamnionitis + fetal hypoxia (n = 10). Umbilical arterial (UmA) and venous (UmV) blood were assayed for IL-1β, IL-2, IL-6, IL-8, TNFα, and IL-10. IL-6 and IL-8 were below assay detection in UmA and UmV blood in Group 1 and increased in Group 2 (P < 0.01), UmA»UmV (P < 0.01). Their concentrations increased further in Groups 3 and 4 (P = 0.003), UmA»UmV. Placental clearance was concentration dependent that approaches saturation in the presence of chorioamnionitis. Marked increases in fetal synthesis of IL-6 and IL-8 occur in chorioamnionitis. Synthesis increase further when complicated by fetal hypoxia. Cytokine removal occurs via placental concentration-dependent mechanisms, potentially contributing to adverse fetal effects. The source and role of the placenta in synthesis and/or clearance of inflammatory mediators in term pregnancies complicated by clinical chorioamnionitis are unclear; however, conventional wisdom suggests the placenta is their source. This is the first study demonstrating that circulating concentrations of fetal IL-6 and IL-8 in clinical chorioamnionitis ± birth asphyxia in term pregnancies are of fetal origin. Circulating fetal inflammatory cytokines are cleared by concentration-dependent placental mechanisms that are nearly saturated in chorioamnionitis ± fetal hypoxia. These observations provide additional insight into understanding the fetal immune response in term pregnancies complicated by clinical chorioamnionitis.

Histological severity of maternal and fetal inflammation is correlated with the prevalence of maternal clinical signs.

To evaluate whether there is a stepwise increase in the prevalence of maternal clinical signs according to the severity of histological inflammation in the chorioamniotic membranes, placenta, and umbilical cord in preterm deliveries. This retrospective study, conducted between January 2007 and May 2017, included patients with preterm delivery between 22 and 33 weeks. The histological findings of maternal/fetal inflammatory responses were staged and graded according to the Amsterdam Placental Workshop Group consensus statement. Correlations between the histological severity of maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and clinical signs were evaluated using the Cochran-Armitage trend test. A total of 138 patients were included. The stage and grade of the maternal inflammatory response were correlated with earlier gestational weeks at delivery and lighter birth weight. The prevalence of clinical chorioamnionitis was significantly correlated with a higher stage and grade of the maternal inflammatory response (Gibbs/Lencki criteria: 15.8%/15.8% in Stage 3, 16.3%/14% in Grade 2). No significant correlations were observed between gestational weeks at delivery and birth weight and stage/grade of fetal inflammatory response. The prevalence of clinical chorioamnionitis was significantly correlated with higher stage and grade of fetal inflammatory response (Gibbs/Lencki criteria: 25%/25% in Stage 3 and 29.4%/29.4% in Grade 2). Correlations exist between the severity of histological maternal/fetal inflammatory responses and the prevalence of clinical chorioamnionitis and positive maternal clinical signs in preterm deliveries. However, the prevalence of clinical chorioamnionitis was 20%-30% even in the most severe fetal inflammatory responses.

Perinatal Risk Factors for the Development of Neonatal Intraventricular Hemorrhage in Preterm Infants

Background: To evaluate the impact perinatal factors closely related to the development of neonatal intraventricular hemorrhage (IVH) in preterm infants. Methods: A retrospective case-control study was performed on premature infants born in our perinatal center in 2014–2018. Neonates with IVH were age-matched with normal controls (1:5). Perinatal factors were compared between cases and controls. Results: Fourteen cases and 70 controls had a median of 26.5 (range 22–29) weeks gestational age. Significant difference was observed regarding the incidence of clinical chorioamnionitis (43% and 14%, p = 0.023) and the use of magnesium sulfate (MgSO4) (14% and 51%, p = 0.017). Adjusted odds ratios (95% confidence interval) were 8.3 (1.8–38) in clinical chorioamnionitis and 0.15 (0.03–0.76) in magnesium sulfate. Conclusions: Relevant perinatal factor of IVH in premature infants born before 30 weeks of gestation was strongly associated with clinical chorioamnionitis. Furthermore, MgSO4 exposure suggested a neuroprotective effect against IVH.