Placental pathology and neonatal morbidity: exploring the impact of gestational age at birth.

AIM: To evaluate placental pathology in term and post-term births, investigate differences in clinical characteristics, and assess the risk of adverse neonatal outcome. METHODS: This prospective observational study included 315 singleton births with gestational age (GA) > 36 weeks + 6 days meeting the local criteria for referral to placental histopathologic examination. We applied the Amsterdam criteria to classify the placentas. Births were categorized according to GA; early-term (37 weeks + 0 days to 38 weeks + 6 days), term (39 weeks + 0 days to 40 weeks + 6 days), late-term (41 weeks + 0 days to 41 weeks + 6 days), and post-term births (≥ 42 weeks + 0 days). The groups were compared regarding placental pathology findings and clinical characteristics. Adverse neonatal outcomes were defined as 5-minute Apgar score < 7, umbilical cord artery pH < 7.0, admission to the neonatal intensive care unit or intrauterine death. A composite adverse outcome included one or more adverse outcomes. The associations between placental pathology, adverse neonatal outcomes, maternal and pregnancy characteristics were evaluated by logistic regression analysis. RESULTS: Late-term and post-term births exhibited significantly higher rates of histologic chorioamnionitis (HCA), fetal inflammatory response, clinical chorioamnionitis (CCA) and transfer to neonatal intensive care unit (NICU) compared to early-term and term births. HCA and maternal smoking in pregnancy were associated with adverse outcomes in an adjusted analysis. Nulliparity, CCA, emergency section and increasing GA were all significantly associated with HCA. CONCLUSIONS: HCA was more prevalent in late and post-term births and was the only factor, along with maternal smoking, that was associated with adverse neonatal outcomes. Since nulliparity, CCA and GA beyond term are associated with HCA, this should alert the clinician and elicit continuous intrapartum monitoring for timely intervention.

Can the use of azithromycin during labour reduce the incidence of infection among puerperae and newborns? A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This systematic review and meta-analysis investigated whether the use of azithromycin during labour or caesarean section reduces the incidence of sepsis and infection among mothers and newborns. DATA SOURCES: We independently searched the PubMed, Web of Science, Cochrane Library and EMBASE databases for relevant studies published before February, 2024. METHODS: We included RCTs that evaluated the effect of prenatal oral or intravenous azithromycin or placebo on intrapartum or postpartum infection incidence. We included studies evaluating women who had vaginal births as well as caesarean sections. Studies reporting maternal and neonatal infections were included in the current analysis. Review Manager 5.4 was used to analyse 6 randomized clinical trials involving 44,448 mothers and 44,820 newborns. The risk of bias of each included study was assessed using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions.Primary outcomes included the incidence of maternal sepsis and all-cause mortality and neonatal sepsis and all-cause mortality; secondary outcomes included maternal (endometritis, wound and surgical site infections, chorioamnionitis, and urinary tract infections) and neonatal outcomes (infections of the eyes, ears and skin). A random-effects model was used to test for overall effects and heterogeneity. RESULTS: The pooled odds ratios (ORs) were as follows: 0.65 for maternal sepsis (95% CI, 0.55-0.77; I2, 0%; P < .00001); 0.62 for endometritis (95% CI, 0.52-0.74; I2, 2%; P < .00001); and 0.43 for maternal wound or surgical site infection (95% CI, 0.24-0.78; P < .005); however, there was great heterogeneity among the studies (I2, 75%). The pooled OR for pyelonephritis and urinary tract infections was 0.3 (95% CI, 0.17-0.52; I2, 0%; P < .0001), and that for neonatal skin infections was 0.48 (95% CI, 0.35-0.65; I2, 0%, P < .00001). There was no significant difference in maternal all-cause mortality or incidence of chorioamnionitis between the two groups. No significant differences were observed in the incidence of neonatal sepsis or suspected sepsis, all-cause mortality, or infections of the eyes or ears. CONCLUSION: In this meta-analysis, azithromycin use during labour reduced the incidence of maternal sepsis, endometritis, incisional infections and urinary tract infections but did not reduce the incidence of neonatal-associated infections, except for neonatal skin infections. These findings indicate that azithromycin may be potentially beneficial for maternal postpartum infections, but its effect on neonatal prognosis remains unclear. Azithromycin should be used antenatally only if the clinical indication is clear and the potential benefits outweigh the harms.

Relationship between chorioamnionitis or funisitis and lung injury among preterm infants: meta-analysis involved 16 observational studies with 68,397 participants.

BACKGROUND: Chorioamnionitis (CA) can cause multiple organ injuries in premature neonates, particularly to the lungs. Different opinions exist regarding the impact of intrauterine inflammation on neonatal respiratory distress syndrome (NRDS) and bronchopulmonary dysplasia (BPD). We aim to systematically review the relationship between CA or Funisitis (FV) and lung injury among preterm infants. METHODS: We electronically searched PubMed, EMbase, the Cochrane library, CNKI, and CMB for cohort studies from their inception to March 15, 2023. Two reviewers independently screened literature, gathered data, and did NOS scale of included studies. The meta-analysis was performed using RevMan 5.3. RESULTS: Sixteen observational studies including 68,397 patients were collected. Meta-analysis showed CA or FV increased the lung injury risk (OR = 1.43, 95%CI: 1.06-1.92). Except for histological chorioamnionitis (HCA) (OR = 0.72, 95%CI: 0.57-0.90), neither clinical chorioamnionitis (CCA) (OR = 1.86, 95%CI: 0.93-3.72) nor FV (OR = 1.23, 95%CI: 0.48-3.15) nor HCA with FV (OR = 1.85, 95%CI: 0.15-22.63) had statistical significance in NRDS incidence. As a result of stratification by grade of HCA, HCA (II) has a significant association with decreased incidence of NRDS (OR = 0.48, 95%CI: 0.35-0.65). In terms of BPD, there is a positive correlation between BPD and CA/FV (CA: OR = 3.18, 95%CI: 1.68-6.03; FV: OR = 6.36, 95%CI: 2.45-16.52). Among CA, HCA was positively associated with BPD (OR = 2.70, 95%CI: 2.38-3.07), whereas CCA was not associated with BPD (OR = 2.77, 95%CI: 0.68-11.21). HCA and moderate to severe BPD (OR = 25.38, 95%CI: 7.13-90.32) showed a positive correlation, while mild BPD (OR = 2.29, 95%CI: 0.99-5.31) did not. CONCLUSION: Currently, evidence suggests that CA or FV increases the lung injury incidence in premature infants. For different types of CA and FV, HCA can increase the incidence of BPD while decreasing the incidence of NRDS. And this "protective effect" only applies to infants under 32 weeks of age. Regarding lung injury severity, only moderate to severe cases of BPD were positively correlated with CA.

[Feasibility study of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester].

Objective: To investigate the feasibility of expectant management of different degrees of vaginal fluid in pregnant women with premature rupture of membranes in the second trimester. Methods: A retrospective cohort study was conducted to collect 103 pregnant women who were diagnosed with premature rupture of membranes in the second trimester of pregnancy and insisted on continuing the pregnancy in Shanxi Bethune Hospital from July 2012 to July 2022. According to the degree of vaginal fluid, pregnant women were divided into rupture group (with typical vaginal fluid, 48 cases) and leakage group (without typical vaginal fluid, 55 cases). The rupture latency (the time from rupture of membranes to termination of pregnancy), gestational weeks of termination, indications and methods of termination of pregnancy, maternal infection related indicators and perinatal outcomes were compared between the two groups. Univariate regression model was used to analyze the correlation between different degrees of vaginal fluid in pregnant women with premature rupture of membranes and maternal and neonatal outcomes. Results: (1) Obstetric indicators: there was no significant difference in the gestational age of rupture of membranes between the two groups (P>0.05). However, the proportion of rupture latency >28 days in the leakage group was significantly higher than that in the rupture group [42% (23/55) vs 13% (6/48); χ2=33.673, P<0.001], and the incidence of pregnancy termination ≥28 weeks was significantly higher [47% (26/55) vs 19% (9/48); χ2=9.295, P=0.002]. (2) Indications and methods of termination: the incidence of progressive reduction of amniotic fluid as the indication for termination in the leakage group was significantly lower than that in the rupture group [22% (12/55) vs 42% (20/48); χ2=4.715, P=0.030], and the incidence of full-term termination in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 12% (6/48); χ2=5.008, P=0.025], while there were no significant differences in the indications of termination of pregnancy, including amniotic cavity infection, uterine contraction failure and fetal distress between the two groups (all P>0.05). The incidence of induced labor or spontaneous contraction in the leakage group was significantly lower than that in the rupture group [53% (29/55) vs 81% (39/48); χ2=9.295, P=0.002], while the cesarean section rate and vaginal delivery rate were similar between the two groups (both P>0.05). (3) Infection related indicators: the incidence of amniotic cavity infection in the leakage group was significantly higher than that in the rupture group [31% (17/55) vs 13% (6/48); χ2=4.003, P=0.045]. However, there were no significant differences in the elevation of inflammatory indicators, the positive rate of cervical secretion bacterial culture and the incidence of tissue chorioamnionitis between the two groups (all P>0.05). (4) Perinatal outcomes: the live birth rate in the leakage group was significantly higher than that in the rupture group [51% (28/55) vs 27% (13/48); χ2=5.119, P=0.024]. The proportion of live births with 1-minute Apgar score >7 in the leakage group was significantly higher than that in the rupture group [38% (21/55) vs 17% (8/48); χ2=4.850, P=0.028]. However, there were no significant differences in the birth weight of live births and the incidence of neonatal complications between the two groups (all P>0.05). (5) Univariate regression analysis showed that compared with the rupture group, the leakage group had a higher risk of pregnancy termination at ≥28 gestational weeks (RR=2.521, 95%CI: 1.314-4.838; P=0.002), amniotic infection (RR=2.473, 95%CI: 1.061-5.764; P=0.025), perinatal survival (RR=1.880, 95%CI: 1.104-3.199; P=0.014). Conclusion: Compared with pregnant women with typical vaginal fluid in the second trimester of premature rupture of membranes, expectant treatment for pregnant women with atypical vaginal fluid is more feasible, which could effectively prolong the gestational weeks and improve the perinatal live birth rate.

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

AIMS: Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. METHODS: Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. RESULTS: The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). CONCLUSIONS: Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Clinical Chorioamnionitis and Neurodevelopment at 5 Years of Age in Children Born Preterm: The EPIPAGE-2 Cohort Study.

OBJECTIVE: To assess the association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born preterm. STUDY DESIGN: EPIPAGE 2 is a national, population-based cohort study of children born before 35 weeks of gestation in France in 2011. We included infants born alive between 240/7 and 346/7 weeks after preterm labor or preterm premature rupture of membranes. Clinical chorioamnionitis was defined as maternal fever before labor (>37.8°C) with ≥2 of the following criteria: maternal tachycardia, hyperleukocytosis, uterine contractions, purulent amniotic fluid, or fetal tachycardia. The primary outcome was a composite, including cerebral palsy, coordination disorders, cognitive disorders, sensory disorders, or behavioral disorders. We also analyzed each of these disorders separately as secondary outcomes. We performed a multivariable analysis using logistic regression models. We accounted for the nonindependence of twins and missing data by generalized estimating equation models and multiple imputations, respectively. RESULTS: Among 2927 children alive at 5 years of age, 124 (3%) were born in a context of clinical chorioamnionitis. Overall, 8.2% and 9.6% of children exposed and unexposed, respectively, to clinical chorioamnionitis had moderate-to-severe neurodevelopmental disorders. After multiple imputations and multivariable analysis, clinical chorioamnionitis was not associated with the occurrence of moderate-to-severe neurodevelopmental disorders (aOR, 0.9; 95% CI, 0.5-1.8). CONCLUSIONS: We did not find any association between clinical chorioamnionitis and neurodevelopmental disorders at 5 years of age in children born at <35 weeks of gestation after preterm labor or preterm premature rupture of membrane.

Induction of labor versus expectant management in patients with idiopathic polyhydramnios.

OBJECTIVE: To evaluate whether induction of labor is associated with lower risk of cesarean section compared to expectant management in patients with isolated polyhydramnios. STUDY DESIGN: This is a single-center, retrospective cohort study of patients with pregnancies complicated by idiopathic polyhydramnios, documented between 34 and 38 weeks gestation, who were delivered between July 2012 and February 2020. The primary outcome was cesarean delivery. Secondary outcomes included chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, and composite neonatal morbidity. RESULTS: There were 194 patients included with idiopathic polyhydramnios - 115 underwent induction and 79 patients were expectantly managed. Planned induction was associated with a lower rate of CD compared with expectant management but did not meet statistical significance (19.1 % vs 30.4 %, aOR 0.51, 95 % CI 0.24, 1.05). A similar effect was seen when stratifying for parity: both nulliparous (9.1 % vs 16.3 %, aOR 0.59, 95 % CI 0.17, 1.98) and multiparous (32.7 % vs 47.2 %, aOR 0.45, 95 % CI 0.18, 1.15) patients had a lower CD rate when there was a planned induction, though neither group met statistical significance. No differences in maternal or fetal secondary outcomes were identified (chorioamnionitis, endometritis, postpartum hemorrhage, preeclampsia/gestational hypertension, composite neonatal morbidity). CONCLUSION: Lower rates of cesarean section were associated with labor induction for patients with isolated polyhydramnios, but confidence intervals did not reach statistical significance.

Intrapartum azithromycin to prevent maternal and neonatal sepsis and deaths: A systematic review with meta-analysis.

OBJECTIVES: A systematic review with met-analysis was performed to summarise the evidence on the effect of intrapartum azithromycin on maternal and neonatal infections and deaths. SEARCH STRATEGY: PubMed, Scopus and Web of Science databases were searched in March 2023. SELECTION CRITERIA: Randomised controlled trials comparing intrapartum single-dose of azithromycin with placebo. DATA COLLECTION AND ANALYSIS: Maternal infections, maternal mortality, neonatal sepsis, neonatal mortality. We used the random-effects Mantel-Haenszel method to calculate risk ratios (RR) with 95% confidence intervals (95% CI). We assessed risk of bias of the included studies and estimated the evidence certainty using the GRADE approach. MAIN RESULTS: After screening 410 abstracts, five studies with 44 190 women and 44 565 neonates were included. The risk of bias was low in four and had some concerns in one of the studies. The risk of endometritis was 1.5% in the azithromycin group and 2.3% in the placebo group (RR 0.64, 95% CI 0.55-0.75), and the evidence certainty was high. The respective risk for chorioamnionitis was 0.05% and 0.1% (RR 0.50, 95% CI 0.22-1.18; evidence certainty moderate). The wound infection rate was lower in the azithromycin group (1.6%) than in the placebo group (2.5%), RR 0.52 (95% CI 0.30-0.89; moderate certainty evidence). The maternal sepsis rate was 1.1% in the azithromycin group and 1.7% in the placebo group (RR 0.66, 95% CI 0.56-0.77; evidence certainty high). Mortality rates did not show evidence of a difference (0.09% versus 0.08%; RR 1.26, 95% CI 0.65-2.42; moderate certainty evidence). The neonatal mortality rate was 0.7% in the azithromycin group and 0.8% in the placebo group (RR 0.94, 95% CI 0.76-1.16; moderate certainty evidence). The neonatal sepsis rate was 7.6% in the azithromycin group and 7.4% in the placebo group (RR 1.02, 95% CI 0.96-1.09; moderate certainty evidence). CONCLUSIONS: Intrapartum administration of azithromycin to the mother reduces maternal postpartum infections, including sepsis. Impact on maternal mortality remains undecided. Azithromycin does not reduce neonatal sepsis or mortality rates.

Maternal and neonatal outcomes following magnesium sulfate in the setting of chorioamnionitis: a meta-analysis.

PURPOSE: Magnesium sulfate (MgSO4) has been widely used in obstetrics as a mean to help decrease maternal and neonatal morbidity in various antenatal pathology. As a factor, it seems to regulate immunity and can, thus, predispose to infectious morbidity. To date, it remains unknown if its administration can increase the risk of chorioamnionitis. In the present meta-analysis, we sought to accumulate the available evidence. METHODS: We systematically searched Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL, and Google Scholar databases in our primary search along with the reference lists of electronically retrieved full-text papers. RESULTS: Eight studies were included that investigated the incidence of chorioamnionitis among parturient that received MgSO4 and control patients. Magnesium sulfate was administered in 3229 women and 3330 women served as controls as they did not receive MgSO4. The meta-analysis of data revealed that there was no association between the administration of magnesium sulfate and the incidence of chorioamnionitis (OR 0.98, 95% CI 0.73, 1.32). Rucker's analysis revealed that small studies did not significantly influence the statistical significance of this finding (OR 1.12, 95% CI 0.82, 1.53). Trial sequential analysis revealed that the required number to safely interpret the primary outcome was not reached. Two studies evaluated the impact of MgSO4 in neonates delivered in the setting of chorioamnionitis. Neither of these indicated the presence of a beneficial effect in neonatal morbidity, including the risk of cerebral palsy, intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, stillbirth, or neonatal death. CONCLUSION: Current evidence indicates that magnesium sulfate is not associated with an increased risk of maternal chorioamnionitis. However, it should be noted that its effect on neonatal outcomes of offspring born in the setting of chorioamnionitis might be subtle if any, although the available evidence is very limited.

Relationship between vaginal microbiota and chorioamnionitis: A prospective cohort study.

OBJECTIVE: This study aimed to determine the association between vaginal microbiota and chorioamnionitis and its predictive value. METHODS: Thirty pregnant women in their third trimester were prospectively recruited. The participants were categorized into three groups based on their clinical manifestations and placental pathology: the clinical chorioamnionitis group (IP group), the asymptomatic histological chorioamnionitis group (CP group), and the healthy control group (CN group). Basic data and medical history were collected from each participant. Vaginal samples were collected before delivery and analyzed using microbial diversity sequencing. RESULTS: No significant differences were observed in age, body mass index, and education among the groups (P > 0.05). However, the IP group exhibited higher rates of low birth weight (60 % vs 20 % vs 0 %, P = 0.008) and respiratory distress syndrome (50 % vs 20 % vs 0 %, P = 0.003) compared with the CP and CN groups. The Shannon index [2.09 (1.16-3.86) vs 0.84 (0.19-1.11) vs 0.44 (0.25-0.85), P = 0.009] and Simpson index [0.70 (0.41-0.81) vs 0.26 (0.04-0.39) vs 0.11 (0.05-0.29), P = 0.010] in the IP group were higher than those in the CN and CP groups. ß diversity analysis indicated that the microbial community structure differed among the three groups, with a 14.1 % variation associated with group differences (P = 0.002). At the genus level, the random forest model revealed that Lactobacillus, Dialister, Prevotella, Ligilactobacillus, and Anaerococcus had Gini indexes higher than 1. Further, linear discriminant analysis (LDA) demonstrated that the abundance of Lactobacillus crispatus in the IP group was lower than in the CN group (LDA >4.0, mean relative abundance 9.19 % vs 54.40 %, P = 0.031). The logistic regression analysis indicated that a decreased abundance of L. crispatus was associated with an increased risk of clinical chorioamnionitis. CONCLUSIONS: The reduction of L. crispatus and increasing trend of specific anaerobic groups are associated with the onset of chorioamnionitis, suggesting their potential value in chorioamnionitis identification. The vaginal microbiota could serve as a useful biomarker for predicting future disease and tailoring surveillance efforts. Additionally, it may present a viable target for developing prevention and therapeutic strategies.

Performance Characteristics of Sepsis Screening Tools During Delivery Admissions.

OBJECTIVE: To evaluate the screening performance characteristics of existing tools for the diagnosis of sepsis during delivery admissions. METHODS: This was a case-control study using electronic health record data, including vital signs and laboratory results, for all delivery admissions of patients with sepsis from 59 nationally distributed hospitals. Patients with sepsis were matched by gestational age at delivery in a 1:4 ratio with patients without sepsis to create a comparison group. Patients with chorioamnionitis and sepsis were compared with a complete cohort of patients with chorioamnionitis without sepsis. Multiple screening criteria for sepsis were evaluated: the CMQCC (California Maternal Quality Care Collaborative), SIRS (Systemic Inflammatory Response Syndrome), the MEWC (the Maternal Early Warning Criteria), UKOSS (United Kingdom Obstetric Surveillance System), and the MEWT (Maternal Early Warning Trigger Tool). Sensitivity, false-positive rates, and C-statistics were reported for each screening tool. Analyses were stratified into cohort 1, which excluded patients with chorioamnionitis-endometritis, and cohort 2, which included those patients. RESULTS: Delivery admissions at 59 hospitals were extracted for patients with sepsis. Cohort 1 comprised 647 patients with sepsis, including 228 with end-organ injury, matched with a control group of 2,588 patients without sepsis. Cohort 2 comprised 14,591 patients with chorioamnionitis-endometritis, of whom 1,049 had sepsis and 238 had end-organ injury. In cohort 1, the CMQCC and the UKOSS pregnancy-adjusted criteria had the lowest false-positive rates (6.9% and 9.6%, respectively) and the highest C-statistics (0.92 and 0.91, respectively). Although other screening criteria, such as SIRS and the MEWC, had similar sensitivities, it was at the cost of much higher false-positive rates (21.3% and 38.3%, respectively). In cohort 2, including all patients with chorioamnionitis-endometritis, the highest C-statistics were again for the CMQCC (0.67) and UKOSS (0.64). All screening tools had high false-positive rates, but the false-positive rates for the CMQCC and UKOSS were substantially lower than those for SIRS and the MEWC. CONCLUSION: During delivery admissions, the CMQCC and UKOSS pregnancy-adjusted screening criteria have the lowest false-positive results while maintaining greater than 90% sensitivity rates. Performance of all screening tools was degraded in the setting of chorioamnionitis-endometritis.

Intrauterine Inflammation, Excessive Fetal Growth and Respiratory Morbidities in Moderate-To-Late Preterm Neonates.

INTRODUCTION: Respiratory morbidities in neonates are often progressive and life-threatening, and its early prediction is crucial. Intrauterine inflammation is one of the key control variables of respiratory morbidities in both very preterm and term neonates; however, little is known about its effects in the remaining group of moderate-to-late preterm neonates born between 32+0 and 36+6 weeks of gestation. This study aimed to confirm whether intrauterine inflammation is associated with respiratory morbidities in moderate-to-late preterm neonates. METHODS: A single-center retrospective observational study was conducted in neonates born between 32+0 and 34+6 weeks of gestation between April 2013 and March 2018. The correlation between respiratory morbidities (defined as a requirement for invasive mechanical ventilation longer than the median duration of 3 days) and intrauterine inflammation was assessed using multivariable logistic regression analysis. RESULTS: The study population comprised 242 neonates born at 33.7 ± 0.8 weeks of gestation and weighing 1,936 ± 381 g. The multivariable model to predict the outcome comprised respiratory distress syndrome (odds ratio [OR]: 9.1; 95% confidence interval [CI]: 3.7-22.5; p < 0.001), lower gestational age (per week; OR: 0.5; 95% CI: 0.3-0.8; p < 0.005), higher birth-weight z-score (OR: 1.6; 95% CI: 1.2-2.2; p < 0.005), lower cord blood pH (per 0.10; OR: 0.5; 95% CI: 0.3-0.7; p < 0.005), and chorioamnionitis (OR: 2.8; 95% CI: 1.1-7.2; p < 0.05). CONCLUSION: Together with the incidence of respiratory distress syndrome and gestational age, chorioamnionitis and high birth-weight z-scores were associated with an increased incidence of respiratory morbidities in moderate-to-late preterm neonates. The deleterious impact of intrauterine inflammation on the lungs may be common in neonates of virtually all gestational ages. Traditional admission policy of neonatal intensive care units based on a threshold birth-weight, may leave a group of neonates without close observation despite their increased risks for respiratory morbidities.

Predicting peripartum infection in laboring patients at high risk in Cameroon, Africa.

OBJECTIVE: To develop a predictive model for peripartum infection among high risk laboring patients in Cameroon, Africa. STUDY DESIGN: We conducted a secondary analysis of the Cameroon Antibiotic Prophylaxis Trial (NCT03248297), a multicenter 3-arm double-blind randomized controlled trial of oral azithromycin ± amoxicillin among term pregnancies with prolonged labor or rupture of membranes in Cameroon 1/2018-5/2020. Patients with chorioamnionitis prior to randomization, study drug contraindications, or planned cesarean were excluded. The outcome of interest was a composite of maternal peripartum infection (chorioamnionitis, endometritis, sepsis by World Health Organization criteria, wound infection/abscess) diagnosed up to 6 weeks postpartum. Potential predictors were compared between patients with and without the composite outcome, and evaluated at a 0.05 alpha level. Statistically significant exposures were analyzed using multivariable regression (to generate adjusted odds ratios and 95 % confidence intervals) with backwards selection to generate a parsimonious model. Receiver operating characteristic curves with associated area under the curve assessed the model's predictive ability. A nomogram based on the final best fit multivariable model was constructed. RESULTS: Of 756 patients in the parent trial, 652 were analyzed: 45 (7 %) had peripartum infection. Those with infection were more likely to be nulliparous, lower education level, higher gestational age, receive antibiotics per hospital protocols, and undergo cesarean. In our best-fit multivariable model, none/primary education (vs university), cesarean birth, and antibiotic receipt per physician discretion (vs for cesarean prophylaxis) were significantly associated with increased infection risk. This model was moderately predictive (AUC = 0.75, 95 % CI 0.67-0.82). When using this 3 factor model, for a patient with a cesarean birth, receipt of antibiotics per physician discretion, and university education, the probability of peripartum infection was 35 % (95 % CI 0.11-0.73). CONCLUSIONS: While several variables such as parity are associated with infectious morbidity within 6 weeks among high risk laboring patients in Cameroon, only education level, antibiotic indication, and cesarean birth were independently associated, and a model including these 3 factors was moderately predictive. Validation of our findings in a larger population is warranted.

Significant association between circumvallate placenta, placental abruption and acute chorioamnionitis in preterm birth: A 23-year retrospective cohort study.

AIM: circumvallate placenta, placental abruption and acute chorioamnionitis separately are associated with unfavourable clinical outcomes. We aimed to determine the prevalence and define whether an association exists between the three abnormalities. METHODS: 16,042 placenta pathology reports between 1997 and 2020 from a tertiary care centre in the Netherlands were retrospectively analysed. For the statistical analysis, the chi-square test and bootstrapping were used to evaluate an association. RESULTS: In our cohort the prevalence of circumvallate placenta is 2.2 %, placental abruption cases 4.0 % and acute chorioamnionitis 20.6 %. We observed a statistically significant association between all three placental abnormalities: circumvallate placenta, placental abruption and acute chorioamnionitis. In addition, there was also an association between circumvallate placenta and acute chorioamnionitis. CONCLUSION: Our results show that combined presence of circumvallate placenta, placental abruption and acute chorioamnionitis are associated in preterm birth (p = 0.001). A remarkable finding is that the combination of all three abnormalities (circumvallate placenta, placental abruption and acute chorioamnionitis) was not observed in term pregnancies >37 weeks.

Association of clinical signs of chorioamnionitis with histological chorioamnionitis and neonatal outcomes in women with premature rupture of membranes.

Background: Premature rupture of membrane (PROM), especially when preterm or prolonged is associated with an increased risk of chorioamnionitis with its attendant feto-maternal complications. Aim: The study was aimed to determine the association of clinical signs of chorioamnionitis with histological chorioamnionitis and neonatal outcomes in women with PROM. Materials and Methods: Eligible participants with clinical diagnosis of PROM at gestational age of ≥28 weeks managed between December 2018 and June 2019 were consecutively recruited. Their sociodemographic characteristics, obstetrics history, and evidence of clinical chorioamnionitis using the Gibb's criteria were obtained. Following delivery, chorioamnionitis was histologically confirmed. Primary outcome measure was the proportion of women with PROM and histological chorioamnionitis that were detected clinically. Results: Of the 136 participants analyzed, 108 (79.4%) had term PROM, while 28 (20.6%) had preterm PROM (<37 weeks). The prevalence of histological chorioamnionitis was 50.0% compared to 16.2% using clinical indicators of infection. Histological chorioamnionitis was almost two times higher in preterm than term PROM (71.4% vs 38.9%). About two-third (67.6%) of the chorioamnionitis identified histologically were missed using clinical signs of chorioamnionitis. Clinical signs of chorioamnionitis had specificity of 100.0%, but low sensitivity (35.5%) and accuracy of 70.6%. A combination of three symptoms, maternal pyrexia and tachycardia, and fetal tachycardia appears to be the most reliable clinical indicator of chorioamnionitis in women with preterm PROM. There was a significant association between low birth weight, low Apgar score, NICU admission, and the presence of histological chorioamnionitis in women that had PROM. Conclusion: Clinical signs of chorioamnionitis have a low sensitivity and are not very accuracy in diagnosing chorioamnionitis in women with PROM.

Placental inflammation and pregnancy outcomes: A prospective, observational study in South Asia: The PURPOSe study.

OBJECTIVE: To examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan. DESIGN: Prospective, observational study. SETTING: Three hospitals in India and a large maternity hospital in Pakistan. POPULATION: The enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India. METHODS: A prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards. MAIN OUTCOME MEASURES: Any placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens. RESULTS: In the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000-2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions. CONCLUSIONS: Chorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.

Perinatal risk factors for neonatal early-onset sepsis: a meta-analysis of observational studies.

OBJECTIVE: Early-onset neonatal sepsis (EONS) remains an important cause of neonatal mortality and has many risk factors, therefore, this study aimed to investigate the perinatal risk factors for EONS. METHODS: We searched CNKI, Wan Fang, VIP, CBM, PubMed, Embase, and Web of Science to compile studies regarding the incidence of neonatal early-onset sepsis, published up to 1 May 2022. To evaluate the quality of the included studies, we used the Newcastle-Ottawa Scale, and the RevMan5.3 software was used for meta-analysis. RESULTS: A total of 17 studies were included, with 1987 cases in the case group and 4814 cases in the control group. Meta-analysis showed that perinatal asphyxia or intrauterine distress (OR = 3.00, 95% CI: 2.18-4.13), amniotic fluid meconium contamination (OR = 4.51, 95% CI: 2.31-8.81), group B streptococcal (GBS) colonization in pregnant women (OR = 2.13, 95% CI: 1.48-3.05), chorioamnionitis (OR = 4.58, 95% CI: 2.61-8.05), premature rupture of membranes (OR = 2.63, 95% CI: 2.09-3.30), lower gestational age (OR = 1.31, 95% CI: 1.18-1.44), maternal urinary or reproductive tract infection (OR = 3.61, 95% CI: 2.14-6.11), perinatal fever (OR = 3.59, 95% CI: 2.25-5.71), very low birth weight (OR = 3.79, 95% CI: 2.14-6.73), and vaginal examination ≥3 times (OR = 7.95, 95% CI: 4.04-15.64) were the perinatal risk factors for EONS. CONCLUSION: Perinatal asphyxia or intrauterine distress, meconium contamination in amniotic fluid, GBS colonization in pregnant women, chorioamnionitis, premature rupture of membranes, lower gestational age, maternal urinary tract or reproductive tract infection, perinatal fever, very low birth weight, and vaginal examinations ≥3 times may increase the risk of EONS.

Association between intracervical Foley balloon and clinical chorioamnionitis among patients with group B streptococcus colonization undergoing induction with standardized labor management.

BACKGROUND: Intracervical Foley balloons are commonly used for cervical ripening, but there has been a historical concern regarding an increased risk of clinical chorioamnionitis with Foley balloon use in patients with group B streptococcus. OBJECTIVE: This study aimed to determine whether intracervical Foley balloon use in patients with group B streptococcus is associated with an increased risk of clinical chorioamnionitis. STUDY DESIGN: This was a secondary analysis of a randomized controlled trial Mechanical and Pharmacologic Methods of Labor Induction: A Randomized Controlled Trial that compared cervical ripening agents within a standardized labor protocol. Foley balloon (alone, with oxytocin, or with misoprostol) was compared with misoprostol only to evaluate the primary outcome of clinical chorioamnionitis, defined based on the American College of Obstetricians and Gynecologists guidelines. Patients with a term, singleton pregnancy with intact membranes and an unfavorable cervix (Bishop score of ≤6 and dilation ≤2 cm) and a known group B streptococcus status were included. The secondary outcomes included a composite postpartum maternal infectious outcome consisting of any occurrence of endometritis, wound infection, postpartum urinary tract infection, or maternal sepsis; additional secondary outcomes included neonatal outcomes. Binomial regression with robust error variance was used to evaluate whether group B streptococcus status modified the relationship between Foley balloon use and clinical chorioamnionitis and to adjust for confounders. RESULTS: A total of 491 patients were enrolled in the original trial. Of these patients, 467 had a known group B streptococcus status and underwent cervical ripening: 182 (39.0%) had group B streptococcus, and 285 (61.0%) did not have group B streptococcus. Moreover, 73.0% of patients received a Foley balloon, and 27.0% of patients did not receive a Foley balloon. There was no difference in the demographic or clinical characteristics between groups. The overall rate of clinical chorioamnionitis was 12.2%, with no difference between those with and without a Foley balloon (12.6% vs 11.1%, respectively; P=.66). Group B streptococcus status did not modify the association between Foley balloon use and clinical chorioamnionitis (relative risk, 0.93; 95% confidence interval, 0.50-1.72). This remained unchanged after adjusting for gestational age (adjusted relative risk, 0.87; 95% confidence interval, 0.45-1.67). Furthermore, other maternal and neonatal outcomes were similar between groups. CONCLUSION: In this secondary analysis of a large randomized trial using a standardized labor protocol, there was no increased risk of infectious morbidity with Foley balloon use in patients overall and in patients with group B streptococcus. Our findings support that a Foley balloon can be safely used for cervical ripening in patients with group B streptococcus colonization.

Morphological study of the placenta in deliveries with pre-eclampsia: Results from a prospective, observational study in India and Pakistan (PURPOSe).

OBJECTIVE: To compare placental findings in women with and without pre-eclampsia. DESIGN: The PURPOSe study included women with stillbirths, women with preterm births and women at term as controls. The placenta of each case was evaluated using the Amsterdam criteria. SETTING: Two sites and five tertiary care hospitals of south Asia (Three in India and two in Pakistan). POPULATION: Pregnancies in India and Pakistan with placental histology including women with documented hypertension and documented proteinuria and women with neither hypertension nor proteinuria. METHODS: We compared the placental findings of the two groups using the Amsterdam criteria and further evaluated the placental findings in women with and without pre-eclampsia who had a stillbirth, preterm live birth, or term live birth (control). MAIN OUTCOME MEASURES: The main outcome measures were the frequency of maternal and fetal vascular malperfusion and the frequency of placental inflammation and its components, chorioamnionitis, funisitis, villitis and intervillitis in women with and without pre-eclampsia. RESULTS: A total of 733 women had pre-eclampsia and 2334 women had neither hypertension nor proteinuria. In the placentas of women with pre-eclampsia, 57.3% had maternal vascular malperfusion compared with 37.1% in women without pre-eclampsia (p < 0.0001). There was not a significant difference in the prevalence of fetal vascular hypertension between mothers with (17.1%) and without (14.8%, p = 0.6118) pre-eclampsia. When placentas were classified as 'histologically normal' or not, 61.3% of those from pre-eclamptic pregnancies were classified as abnormal, whereas if there was no pre-eclampsia, only 45.0% were classified as histologically abnormal (p < 0.0001). We also considered rates of placental maternal vascular malperfusion in women with and without pre-eclampsia with stillbirth, preterm neonatal death, and term live birth. In women at term with no pre-eclampsia, 16.7% of the placentas had features of maternal vascular malperfusion. This occurred in 79.9% of women with stillbirths with pre-eclampsia compared with 51.8% of those without pre-eclampsia. Maternal vascular malperfusion was present in 49.7% of preterm live births with pre-eclampsia compared with 33.8% without pre-eclampsia. We also evaluated the inflammatory lesions by whether the mother had or did not have pre-eclampsia. When all inflammatory lesions were considered, women with pre-eclampsia had significantly fewer inflammatory lesions than those women without pre-eclampsia (17.1% versus 23.6% p = 0.001). Each of the specific inflammatory lesions was less common in placentas of women with pre-eclampsia than those with chorioamnionitis (16.1% versus 21.9%, p = 0.004) and funisitis (1.5% versus. 5.1%, p = 0.0004). CONCLUSIONS: Of placental lesions in women with pre-eclampsia, maternal vascular malperfusion was the most common. Inflammatory lesions were less common in women with pre-eclampsia.

Determinants of term premature rupture of membrane: case-control study in Saint Paul's Millennium Medical College Hospital, Addis Ababa, Ethiopia.

BACKGROUND: The term premature rupture of the membranes is the rupture of the membranes before the onset of labor beyond 37 weeks of gestation. Several factors, including obstetric, gynecologic, socioeconomic, and medical, are identified as potential risk factors. This clinical event has detrimental maternal and neonatal complications. OBJECTIVES: This study aimed to investigate the determinants of the term premature rupture of the membranes in Ethiopia. METHODS: This institution-based unmatched case-control study was conducted on 246 women admitted to Saint Paul's hospital millennium medical college from October 2019 to January 2020 (82 cases and 164 controls). Data were collected using an interviewer-based questionnaire and data extraction tools, and data were entered using Epi data 3.1 and analyzed using SPSS 20. The association between independent variables and premature rupture of the membrane was estimated using an odds ratio with 95% confidence intervals and P-value < 0.05. RESULTS: Factors like a history of vaginal discharge (AOR 3.508;95% CI:1.595.7.716), place of Antenatal care follow-up (health center and Mercy Ethiopia) (AOR 5.174;95% CI:2.165,12.362), the previous history of rupture of membrane (AOR 9.955;95% CI:3.265,20.35), and gestational age (AOR 3.018;95% CI:1.338,6.811) were associated with term premature rupture of membrane. There were more maternal and neonatal complications, including puerperal sepsis, wound infection, anemia/PPH, a hospital stays of more than seven days, clinical amnionitis, neonatal hypoglycemia, early onset neonatal sepsis, and respiratory distress encountered by women who presented with premature rupture of membrane. CONCLUSION: Proper screening, close monitoring, and early interventions in those mothers with identified risk factors would help to reduce its negative consequences. Moreover, the provision of continuous professional skill development and improving the quality of ANC service is needed.