Evaluation of fetal cardiac output in preterm premature rupture of membranes.

AIM: We aimed to investigate fetal cardiac output (CO) in pregnancies with preterm premature rupture of membranes (PPROM) and its relationship with umbilical cord pH. METHODS: This was a prospective study in total 90 pregnancies at 24-37 weeks gestation including 42 pregnancies with PPROM and 48 that healthy controls. Fetal cardiac function including combined, left and right CO z-scores were compared. The neonates in the PPROM group were separated with umbilical cord pH above and below 7.25, and cardiac output was compared between groups. RESULTS: In PPROM group, CCO z-score, left cardiac output (LCO) z-score, and right cardiac output (RCO) were significantly lower compared to healthy pregnancies (p = .036, p = .001, p = .032, respectively), while RCO z-score showed no significant differences between the two groups. The aortic annulus and pulmonary artery annulus z-scores were measured smaller in the PPROM group (p = .000 and p = .001, respectively). In PPROM group, the fetal LCO z-score was significantly lower in neonates with an umbilical cord pH of 7.25 or less (p = .048). CONCLUSION: This study provides evidence that fetal CCO is lower in PPROM compared with healthy pregnancies. Reduced LCO z-scores may be useful for predicting adverse neonatal outcomes in pregnancies with PPROM.

Vaginal and neonatal microbiota in pregnant women with preterm premature rupture of membranes and consecutive early onset neonatal sepsis.

BACKGROUND: Preterm premature rupture of membranes (PPROM), which is associated with vaginal dysbiosis, is responsible for up to one-third of all preterm births. Consecutive ascending colonization, infection, and inflammation may lead to relevant neonatal morbidity including early-onset neonatal sepsis (EONS). The present study aims to assess the vaginal microbial composition of PPROM patients and its development under standard antibiotic therapy and to evaluate the usefulness of the vaginal microbiota for the prediction of EONS. It moreover aims to decipher neonatal microbiota at birth as possible mirror of the in utero microbiota. METHODS: As part of the PEONS prospective multicenter cohort study, 78 women with PPROM and their 89 neonates were recruited. Maternal vaginal and neonatal pharyngeal, rectal, umbilical cord blood, and meconium microbiota were analyzed by 16S rRNA gene sequencing. Significant differences between the sample groups were evaluated using permutational multivariate analysis of variance and differently distributed taxa by the Mann-Whitney test. Potential biomarkers for the prediction of EONS were analyzed using the MetaboAnalyst platform. RESULTS: Vaginal microbiota at admission after PPROM were dominated by Lactobacillus spp. Standard antibiotic treatment triggers significant changes in microbial community (relative depletion of Lactobacillus spp. and relative enrichment of Ureaplasma parvum) accompanied by an increase in bacterial diversity, evenness and richness. The neonatal microbiota showed a heterogeneous microbial composition where meconium samples were characterized by specific taxa enriched in this niche. The vaginal microbiota at birth was shown to have the potential to predict EONS with Escherichia/Shigella and Facklamia as risk taxa and Anaerococcus obesiensis and Campylobacter ureolyticus as protective taxa. EONS cases could also be predicted at a reasonable rate from neonatal meconium communities with the protective taxa Bifidobacterium longum, Agathobacter rectale, and S. epidermidis as features. CONCLUSIONS: Vaginal and neonatal microbiota analysis by 16S rRNA gene sequencing after PPROM may form the basis of individualized risk assessment for consecutive EONS. Further studies on extended cohorts are necessary to evaluate how far this technique may in future close a diagnostic gap to optimize and personalize the clinical management of PPROM patients. TRIAL REGISTRATION: NCT03819192, ClinicalTrials.gov. Registered on January 28, 2019.

Clinical audit of the management and outcomes of preterm pre-labour rupture of membranes at Aminu Kano Teaching Hospital.

Introduction: preterm pre-labour rupture of membranes (PPROM) is one of the important causes of preterm birth that can result in high perinatal morbidity and mortality along with maternal morbidity. The purpose of the study was to audit the management of women presenting with Preterm pre-labour rupture of membranes in Aminu Kano Teaching Hospital (AKTH). Methods: this was a retrospective audit on patients admitted with PPROM in AKTH over a period of 24 months. Data was analysed using SPSS version 22 and presented using percentages and compared with the audit standard. Chi-squared test was used to test for association (p-value <0.05). Results: the mean gestational age was 33.27±2.42 weeks. Diagnosis was made on all patients through history and clinical examination. Almost all patients received a course of erythromycin (88%), corticosteroid (84%) and magnesium sulphate (86%). Vaginal delivery was achieved in 57%. About 60% of the neonates were premature, 78% had Apgar score >7 at 5 mins, 50% were admitted in the special care baby unit and 72% survived. Chorioamnionitis and puerperal sepsis occurred in 8% and 21.7% of the mothers. Prolonged PPROM of >24 hours was statistically significantly associated with puerperal sepsis (χ2=7.218; p = 0.007) and perinatal mortality (χ2= 11.505, p = 0.001). Conclusion: despite high fidelity to institutional clinical practice guidelines in Aminu Kano Teaching Hospital there seems to be poor maternal and neonatal outcome with high perinatal mortality. Thus the guidelines need to be reviewed in context of improving the outcome.

Toward a new taxonomy of obstetrical disease: improved performance of maternal blood biomarkers for the great obstetrical syndromes when classified according to placental pathology.

BACKGROUND: The major challenge for obstetrics is the prediction and prevention of the great obstetrical syndromes. We propose that defining obstetrical diseases by the combination of clinical presentation and disease mechanisms as inferred by placental pathology will aid in the discovery of biomarkers and add specificity to those already known. OBJECTIVE: To describe the longitudinal profile of placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), and the PlGF/sFlt-1 ratio throughout gestation, and to determine whether the association between abnormal biomarker profiles and obstetrical syndromes is strengthened by information derived from placental examination, eg, the presence or absence of placental lesions of maternal vascular malperfusion. STUDY DESIGN: This retrospective case cohort study was based on a parent cohort of 4006 pregnant women enrolled prospectively. The case cohort of 1499 pregnant women included 1000 randomly selected patients from the parent cohort and all additional patients with obstetrical syndromes from the parent cohort. Pregnant women were classified into six groups: 1) term delivery without pregnancy complications (n=540; control); 2) preterm labor and delivery (n=203); 3) preterm premature rupture of the membranes (n=112); 4) preeclampsia (n=230); 5) small-for-gestational-age neonate (n=334); and 6) other pregnancy complications (n=182). Maternal plasma concentrations of PlGF and sFlt-1 were determined by enzyme-linked immunosorbent assays in 7560 longitudinal samples. Placental pathologists, masked to clinical outcomes, diagnosed the presence or absence of placental lesions of maternal vascular malperfusion. Comparisons between mean biomarker concentrations in cases and controls were performed by utilizing longitudinal generalized additive models. Comparisons were made between controls and each obstetrical syndrome with and without subclassifying cases according to the presence or absence of placental lesions of maternal vascular malperfusion. RESULTS: 1) When obstetrical syndromes are classified based on the presence or absence of placental lesions of maternal vascular malperfusion, significant differences in the mean plasma concentrations of PlGF, sFlt-1, and the PlGF/sFlt-1 ratio between cases and controls emerge earlier in gestation; 2) the strength of association between an abnormal PlGF/sFlt-1 ratio and the occurrence of obstetrical syndromes increases when placental lesions of maternal vascular malperfusion are present (adjusted odds ratio [aOR], 13.6 vs 6.7 for preeclampsia; aOR, 8.1 vs 4.4 for small-for-gestational-age neonates; aOR, 5.5 vs 2.1 for preterm premature rupture of the membranes; and aOR, 3.3 vs 2.1 for preterm labor (all P<0.05); and 3) the PlGF/sFlt-1 ratio at 28 to 32 weeks of gestation is abnormal in patients who subsequently delivered due to preterm labor with intact membranes and in those with preterm premature rupture of the membranes if both groups have placental lesions of maternal vascular malperfusion. Such association is not significant in patients with these obstetrical syndromes who do not have placental lesions. CONCLUSION: Classification of obstetrical syndromes according to the presence or absence of placental lesions of maternal vascular malperfusion allows biomarkers to be informative earlier in gestation and enhances the strength of association between biomarkers and clinical outcomes. We propose that a new taxonomy of obstetrical disorders informed by placental pathology will facilitate the discovery and implementation of biomarkers as well as the prediction and prevention of such disorders.

Results of expectant management in singleton and twin pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVES: This study aimed to examine whether expectant management in twin pregnancies with preterm premature rupture of membranes (pPROM) is as safe as in singleton pregnancies. MATERIAL AND METHODS: It was a retrospective cohort study comparing pregnancy course and outcome in singleton (n = 299) and twin pregnancies (n = 49) complicated by preterm premature rupture of membranes. Analysed factors included maternal diseases, gestational age at premature rupture of membranes (PROM), management during hospitalization, latency periods between PROM and delivery, gestational age at delivery, neonatal management and outcome. RESULTS: The difference in the proportion of patients with latency up to 72 hours, latency between 72 hours and seven days, and latency exceeding seven days were insignificant. The percentage of patients who received intravenous tocolysis and antenatal corticosteroids were similar; however, patients in twin pregnancies more often received incomplete steroids dose (p = 0.01). The occurrence of the positive non-stress test result and signs of intrauterine infection were similar between the groups. No statistically significant differences in the prevalence of neonatal complications except transient tachypnoea of the newborn were identified (24% in the singleton vs 13% in the twin group, p = 0.03). CONCLUSIONS: Expectant management of pPROM in singleton and twin pregnancies results in similar perinatal and neonatal outcome. Consequently, in case of no evident contraindications, expectant management of twin pregnancies seems to be equally as safe as in singleton pregnancies. Patients in twin pregnancies may be at higher risk of delivery before administration of full antenatal corticosteroids dose, therefore require immediate management initiation and transfer to a tertiary referral centre.

Diagnostic accuracy of procalcitonin in maternal plasma to detect early intra-amniotic infection in preterm premature rupture of the membranes with respect of highvaginal swab as gold standard.

OBJECTIVE: To determine the diagnostic accuracy of procalcitonin in maternal plasma to detect early intra-amniotic infection in Preterm premature rupture of the membranes (PPROM) with respect of high vaginal swab as gold standard. METHODS: A cross-sectional study was conducted at Liaquat National Hospital, Karachi, from February to August 2017. The blood sample of women with PPROM were collected to measure procalcitonin level. PCT1 and PCT2 were run along with the sample for the accuracy of the results. Sensitivity, specificity, PPV, NPV, and diagnostic accuracy of procalcitonin were calculated taking HVS C/S as gold standard. RESULTS: Out of total 150 women, mean age was 28.78±4.79 years. Mean gestational age was 30.79±3.07 weeks. Mean procalcitonin level was 0.13±0.24 ng/ml. Intra-amniotic infection was diagnosed in 48.7% cases through procalcitonin levels and 51.3% through HVS culture and sensitivity. Sensitivity, Specificity, PPV (Positive predictive value), NPV (Negative predictive value) and accuracy were 87%, 91.8%, 91.78%, 87%, and 89.3% respectively. For females with gestational age ≤32 weeks, sensitivity, specificity, and diagnostic accuracy were 83.9%, 90.4%, and 87.03% respectively. For females with gestational age >32 weeks, sensitivity, specificity, and diagnostic accuracy were 95.2%, 92.5%, and 95.23% respectively. CONCLUSION: Diagnostic accuracy of maternal blood procalcitonin levels were found satisfactory in detection of early intra-amniotic infection in PPROM.

Vaginal probiotics as an adjunct to antibiotic prophylaxis in the management of preterm premature rupture of the membranes.

Preterm birth is a leading cause of perinatal morbidity and mortality and Preterm premature rupture of the membranes (PPROM) is a major risk factor contributing to approximately one third of preterm deliveries. Vaginal infections are often associated with PPROM and are characterised by loss of lactobacillin normal vaginal flora and overgrowth of other pathogenic microorganisms. Probiotics appear to have an emerging role in prolonging pregnancy after PPROM. This trial compared the efficacy of a vaginal probiotic in combination with standard antibiotic prophylaxis versus only antibiotic in prolongation of latency period and on perinatal outcome in cases of PPROM between 24 and 34 weeks. Although no significant difference was observed in the mean latency period (p = 0.937) and mean gestational age at birth (p = 0.863) between the two groups, the overall neonatal outcome was better in the study group. There is need of further large-scale clinical trials to demonstrate effectiveness of probiotics.IMPACT STATEMENTWhat is already known on this subject? PPROM is an important cause of preterm birth. Prematurity leads significant global burden of neonatal morbidity and mortality. Antibiotics in PPROM have a proven benefit to prolong latency period from start of PPROM to birth. Probiotics have a role in improving vaginal flora and reducing infections and have been tried in PPROM.What do the results of this study add? The usefulness of probiotics in prolonging latency period and improving neonatal outcome has been reported in limited trials. In our study it has shown an improvement in neonatal outcome overall but not statistically significant compared to few studies which have reported significant beneficial effects. This might be due to existence of variation in the type of the vaginal microflora in different study population.What are the implications of these findings for clinical practice and/or further research? Preliminary results suggest that use of probiotic may benefit women with PPROM. This also implies need of multicentric larger scales trials with different types of probiotics so as to clarify whether any intervention in vaginal microflora can lead to any benefits in reducing the prematurity and its consequence, both on the neonate and heath care infrastructure.

Interventional resealing of preterm premature rupture of the membranes: a systematic review and meta-analysis.

OBJECTIVE: To compare the effectiveness and outcomes of interventional resealing of membranes, "amniopatch" for spontaneous vs. iatrogenic preterm premature rupture of the membranes (sPPROM and iPPROM). METHODS: We performed a systematic review of literature involving an electronic search of the following databases: Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, and Scopus. An indirect meta-analysis was then performed to compare the obstetric, maternal, fetal, and neonatal outcomes of amniopatch between the sPPROM and iPPROM groups. RESULTS: The mean gestational age (GA) at the time rupture was 17.8 ± 1.8 and 25.2 ± 3.8 weeks for iPPROM and sPPROM, respectively, p = .005. Mean GA at the time of amniopatch procedure was 19.2 ± 2.07 weeks for iPPROM and 23 ± 3.1 weeks of gestation for sPPROM, p = .023. The rates of fluid re-accumulation (sPPROM 26% and iPPROM 53%, p = .09) were comparable between the sPPROM and iPPROM groups. Neonatal outcomes except for the rate of IUFD were also comparable between the groups. The incidence of IUFD was significantly higher in the iPPROM group (ES: 24%; 95% CI: 8.00-44.0%; p < .001), compared to sPPROM (ES: 0%; 95% CI: 0.00-4.00%). Obstetric and maternal outcomes were comparable between the two groups. CONCLUSIONS: Amniopatch appears to be a feasible and safe procedure for PPROM treatment. Further research is warranted to investigate the effectiveness of this procedure and establish a standardized criterion for the appropriate selection of patients that could benefit from this intervention.

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

BACKGROUND: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27+0 to 29+6 weeks' gestation (referred to as "early") for severe and at 30+0 to 31+6 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.059) and 25% (95% confidence interval, 6-46; P=.0091) for moderate and severe hypoplasia. OBJECTIVE: Data from the 2 trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of gestational age at balloon insertion. STUDY DESIGN: Individual participant data from the 2 trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced fetoscopic endoluminal tracheal occlusion centers and were randomized in a 1:1 ratio to either expectant management or fetoscopic endoluminal tracheal occlusion. All received standardized postnatal management. The combined data involved 287 patients (196 with moderate hypoplasia and 91 with severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. The secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (fetoscopic endoluminal tracheal occlusion vs expectant), early balloon insertion (yes vs no), observed over expected lung-to-head ratio, liver herniation (yes vs no), and trial (severe vs moderate). The interaction between intervention and the observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity. RESULTS: For survival to discharge, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these 2 effects, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). The results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% confidence interval, 1.1-2.3) following fetoscopic endoluminal tracheal occlusion with late insertion and 3.2 weeks earlier (95% confidence interval, 2.3-4.1) following fetoscopic endoluminal tracheal occlusion with early insertion compared with expectant management. There was no evidence that the effect of fetoscopic endoluminal tracheal occlusion depended on the observed over expected lung-to-head ratio for any of the endpoints. CONCLUSION: This analysis suggests that fetoscopic endoluminal tracheal occlusion increases survival for both moderate and severe lung hypoplasia. The difference between the results for the Tracheal Occlusion To Accelerate Lung growth trials, when considered apart, may be because of the difference in the time point of balloon insertion. However, the effect of the time point of balloon insertion could not be robustly assessed because of a small sample size and the confounding effect of disease severity. Fetoscopic endoluminal tracheal occlusion with early balloon insertion in particular strongly increases the risk for preterm delivery.

Do Large Uterine Fibroids Impact Pregnancy Outcomes?

OBJECTIVES: We sought to assess the prevalence of fibroids complicating pregnancy among Omani women who delivered and were followed-up at Sultan Qaboos University Hospital (SQUH) and correlate the presence of large fibroids (> 5 cm) with maternal and neonatal outcomes. METHODS: This retrospective cohort study was conducted at the Department of Obstetrics and Gynecology, SQUH, from 1 January 2011 to 31 December 2016. Demographic data included maternal age, gravidity, parity, body mass index (BMI), and history of preterm delivery. Ultrasonographic data included the total number of fibroids, number of fibroids > 5 cm in diameter, and location. The main outcomes measured were preterm delivery, preterm premature rupture of membranes (PPROM), malpresentation, intrauterine growth restriction (IUGR), mode of delivery, postpartum hemorrhage, retained placenta, and cesarean myomectomy. Fetal outcomes included birth weight and Apgar score. We used the chi-square test and t-test to calculate significant outcomes. RESULTS: The total number of deliveries over the study period was 24 800. Among these, 62 women had fibroids complicating pregnancy, giving an overall prevalence of 0.3%. Of the 62 women with documented uterine fibroids, 41 had fibroids > 5 cm in diameter and formed the study group, while the control group included 88 women with no fibroids and normal singleton pregnancies. The mean age, parity, BMI, and history of preterm delivery were comparable. The mean age of the study group was 32.6 years. There was no statistically significant difference in obstetric outcomes between the study and control group in terms of preterm labor (p =0.381), PPROM (p =0.536), malpresentation (p =0.237), IUGR (p =0.059), and retained placenta (p =0.296). Postpartum hemorrhage was significantly higher in the study group (p =0.018), the commonest cause was uterine atony (p =0.007). Women with large fibroids had a significantly increased cesarean section rate (p =0.002), the main indications were obstructed labor and failure to progress (62.5%). Five of the 44 women in the study group (12.8%) underwent cesarean myomectomy. Regarding neonatal outcomes, a statistically significant difference was noted in the Apgar scores. CONCLUSIONS: Fibroids measuring > 5 cm in diameter are more likely to cause obstetric complications and are associated with higher cesarean rates. Pre-conception myomectomy is recommended for women with large fibroids.

Risk Profiling of the Solomon Technique versus Selective Technique of Fetoscopic Laser Surgery for Twin-Twin Transfusion Syndrome.

We evaluated the outcomes and adverse events after fetoscopic laser surgery (FLS) for twin-twin transfusion syndrome (TTTS) using the Solomon technique in comparison to the selective technique. A retrospective analysis of a single-center consecutive cohort of FLS-treated TTTS using the selective (January 2010 to July 2014) and Solomon (August 2014 to December 2017) techniques was performed. Among 395 cases, 227 underwent selective coagulation and 168 underwent the Solomon technique. The incidence rates of recurrent TTTS (Solomon vs. selective: 0% vs. .9%, p = .510) and twin anemia-polycythemia sequence (.6% vs. .4%, p = .670) were very low in both groups. The incidence rates of placental abruption (Solomon vs. selective: 10.7% vs. 3.5%, p = .007) and preterm premature rupture of the membranes (pPROM) with subsequent delivery before 32 weeks (20.2% vs. 7.1%, p < .001) were higher in the Solomon group. The median birth recipient weight was significantly smaller in the Solomon group (1790 g vs. 1933 g, p = .049). The rate of survival of at least one twin was significantly higher in the Solomon group (98.2% vs. 93.8%, p = .046). The Solomon technique and total laser energy were significant risk factors for pPROM (odds ratio: 2.64, 1.07, 95% CI [1.32, 5.28], [1.01, 1.13], p = .006, p = .014, respectively). These findings suggest that the Solomon technique led to superior survival outcomes but increased risks of placental abruption, pPROM and fetal growth impairment. Total laser energy was associated with the occurrence of pPROM. Close attention to adverse events is required for perinatal management after FLS to treat TTTS using the Solomon technique.

Comparison of sonographic fetal weight estimation formulas in patients with preterm premature rupture of membranes.

BACKGROUND: Estimation of fetal weight (EFW) by ultrasound is useful in clinical decision-making. Numerous formulas for EFW have been published but have not been validated in pregnancies complicated by preterm premature rupture of membranes (PPROM). The purpose of this study is to compare the accuracy of EFW formulas in patients with PPROM, and to further evaluate the performance of the most commonly used formula - Hadlock IV. METHODS: A retrospective cohort study of women with singleton gestations and PPROM, admitted to a single tertiary center between 2005 and 2017 from 220/7-330/7 (n = 565). All women had an EFW within 14 days of delivery by standard biometry (biparietal diameter, head circumference, abdominal circumference and femur length). The accuracy of previously published 21 estimated EFW formulas was assessed by comparing the Pearson correlation with actual birth weight, and calculating the random error, systematic error, proportion of estimates within 10% of birth weight, and Euclidean distance. RESULTS: The mean gestational was 26.8 ± 2.4 weeks at admission, and 28.2 ± 2.6 weeks at delivery. Most formulas were strongly correlated with actual birth weight (r > 0.9 for 19/21 formulas). Mean systematic error was - 4.30% and mean random error was 14.5%. The highest performing formula, by the highest proportion of estimates and lowest Euclidean distance was Ott (1986), which uses abdominal and head circumferences, and femur length. However, there were minimal difference with all of the first 10 ranking formulas. The Pearson correlation coefficient for the Hadlock IV formula was strong at r = 0.935 (p < 0.001), with 319 (56.5%) of measurements falling within 10%, 408 (72.2%) within 15% and 455 (80.5%) within 20% of actual birth weight. This correlation was unaffected by gender (r = 0.936 for males, r = 0.932 for females, p < 0.001 for both) or by amniotic fluid level (r = 0.935 for mean vertical pocket < 2 cm, r = 0.943 for mean vertical pocket ≥2 cm, p < 0.001 for both). CONCLUSIONS: In women with singleton gestation and PPROM, the Ott (1986) formula for EFW was the most accurate, yet all of the top ten ranking formulas performed quite well. The commonly used Hadlock IV performed quite similarly to Ott's formula, and is acceptable to use in this specific setting.

A specific bacterial DNA signature in the vagina of Australian women in midpregnancy predicts high risk of spontaneous preterm birth (the Predict1000 study).

BACKGROUND: Intrauterine infection accounts for a quarter of the cases of spontaneous preterm birth; however, at present, it is not possible to efficiently identify pregnant women at risk to deliver preventative treatments. OBJECTIVE: This study aimed to establish a vaginal microbial DNA test for Australian women in midpregnancy that will identify those at increased risk of spontaneous preterm birth. STUDY DESIGN: A total of 1000 women with singleton pregnancies were recruited in Perth, Australia. Midvaginal swabs were collected between 12 and 23 weeks' gestation. DNA was extracted for the detection of 23 risk-related microbial DNA targets by quantitative polymerase chain reaction. Obstetrical history, pregnancy outcome, and demographics were recorded. RESULTS: After excluding 64 women owing to losses to follow-up and insufficient sample for microbial analyses, the final cohort consisted of 936 women of predominantly white race (74.3%). The overall preterm birth rate was 12.6% (118 births); the spontaneous preterm birth rate at <37 weeks' gestation was 6.2% (2.9% at ≤34 weeks' gestation), whereas the preterm premature rupture of the membranes rate was 4.2%. No single individual microbial target predicted increased spontaneous preterm birth risk. Conversely, women who subsequently delivered at term had higher amounts of Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii DNA in their vaginal swabs (13.8% spontaneous preterm birth vs 31.2% term; P=.005). In the remaining women, a specific microbial DNA signature was identified that was strongly predictive of spontaneous preterm birth risk, consisting of DNA from Gardnerella vaginalis (clade 4), Lactobacillus iners, and Ureaplasma parvum (serovars 3 and 6). Risk prediction was improved if Fusobacterium nucleatum detection was included in the test algorithm. The final algorithm, which we called the Gardnerella Lactobacillus Ureaplasma (GLU) test, was able to detect women at risk of spontaneous preterm birth at <37 and ≤34 weeks' gestation, with sensitivities of 37.9% and 44.4%, respectively, and likelihood ratios (plus or minus) of 2.22 per 0.75 and 2.52 per 0.67, respectively. Preterm premature rupture of the membranes was more than twice as common in GLU-positive women. Adjusting for maternal demographics, ethnicity, and clinical history did not improve prediction. Only a history of spontaneous preterm birth was more effective at predicting spontaneous preterm birth than a GLU-positive result (odds ratio, 3.6). CONCLUSION: We have identified a vaginal bacterial DNA signature that identifies women with a singleton pregnancy who are at increased risk of spontaneous preterm birth and may benefit from targeted antimicrobial therapy.

Comparison of maternal characteristics, pregnancy course, and neonatal outcome in preterm births with and without prelabor rupture of membranes.

OBJECTIVES: The aim of this study was to evaluate pregnancy outcome of patients with prelabor rupture of membranes receiving expectant management and giving birth prematurely in comparison to preterm births of patients with intact membranes. MATERIAL AND METHODS: It was a retrospective cohort study comparing maternal and neonatal outcome in two groups of preterm births. The first group included 299 consecutive singleton preterm births complicated by prelabor rupture of membranes. The second group consisted of 349 consecutive singleton preterm births without prelabor rupture of membranes. RESULTS: Patients without pPROM underwent Caesarean sections more often than women from the pPROM group (65.3% vs 45.2%; p < 0.001). No statistically significant differences regarding the gestational age during delivery were identified. Lower birth weight was detected in the group with no history of pPROM (p < 0.001). No differences regarding early-onset sepsis were identified and higher percentage of late-onset infections was observed in infants with no history of pPROM (8.9% vs 4.7%; p = 0.04). Pulmonary hypertension was more common in the infants from the pPROM group (4% vs 1.4%; p = 0.049). Neonatal respiratory distress syndrome and respiratory failure were more prevalent in cases of no pPROM history - 20% vs 12.7% (p = 0.02) and 40% vs 25.8% (p < 0.001), respectively. CONCLUSIONS: Development of multiple complications in preterm neonates may be more associated with the management, gestational age at birth, and birth weight than with the occurrence of preterm prelabor rupture of membranes.

Successful treatment of severe intra-amniotic inflammation and cervical insufficiency with continuous transabdominal amnioinfusion and cerclage: A case report.

Severe intra-amniotic inflammation, even with a negative bacterial culture, can lead to premature labor. We report a 43-year-old multiparous woman with severe intra-amniotic inflammation and cervical insufficiency at 23 weeks and 5 days of gestation. Continuous transabdominal amnioinfusion was started 2 days after the diagnosis. The amniotic fluid interleukin-6 level normalized after 2 days of treatment. She underwent Shirodkar cervical cerclage on day 7. Despite termination of amnioinfusion and catheter removal on day 16, the pregnancy was maintained without any subsequent treatment. At 33 weeks and 5 days of gestation, an intrauterine Ureaplasma parvum infection and the onset of contractions led to repeat cesarean delivery. The birth weight was 2292 g, and the Apgar scores were 8/8. Both mother and infant had good outcomes. Continuous transabdominal amnioinfusion may have eliminated factors causing intra-amniotic inflammation, thereby prolonging the pregnancy and improving the infant's prognosis.

A cut-off value for systemic immune-inflammation index in the prediction of adverse neonatal outcomes in preterm premature rupture of the membranes.

AIM: To determine a cut-off value for systemic immune-inflammation index (SII)(neutrophil × platelet /lymphocyte) in the prediction of adverse neonatal outcomes in preterm premature rupture of the membranes (PPROM). METHODS: This retrospective cohort study was conducted among singleton pregnancies with PPROM. Cases were divided into two main groups: Group 1) PPROM diagnosed at 24th-28th weeks of gestation and Group 2) PPROM diagnosed at >28th-34th weeks of gestation. Thereafter, main study groups were divided into two subgroups: Subgroup A: pregnancies with favorable neonatal outcomes and Subgroup B: pregnancies with composite adverse neonatal outcomes. Subgroups were compared in terms of demographic features, clinical characteristics, laboratory test results and SII values. Furthermore, cut-off values of SII for the prediction of composite adverse neonatal outcomes were determined for two main groups. A Mann-Whitney U test was conducted to compare the median values and the chi-square test was used to compare categorical variables among the groups. Receiver operating characteristic (ROC) curves were used to assess the performance of SII value in predicting composite adverse neonatal outcomes. RESULTS: Significant differences were observed for median platelet and SII values between the subgroups (P < 0.001 for both in group 1 and P = 0.002 and P = 0.005, respectively, in group 2). Cut-off values of 1695.14 109 /L (83.3% sensitivity, 85.7% specificity) and 1430.90 × 109 /L (71.4% sensitivity, 75.7% specificity) for composite adverse neonatal outcomes were determined, respectively in group 1 and 2 according to the ROC curve analysis. CONCLUSION: SII may be used as an additional indicator for the prediction of adverse neonatal outcomes in PPROM.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth.

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB). METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy. RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633-5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915-405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy. CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

A pilot randomized controlled trial of complete bed rest versus activity restriction after preterm premature rupture of the membranes.

OBJECTIVE: To assess the impact of bed rest on maternal and neonatal outcomes in pregnancies complicated by preterm premature rupture of the membranes (PPROM), enabling proper sample size calculation for a powered randomized controlled trial (RCT). STUDY DESIGN: We conducted a pilot unblinded randomized controlled trial with a 1:1 allocation ratio (complete bed rest vs activity restriction groups) on singleton pregnancies complicated by PPROM at 24 + 0-33 + 6 weeks. Maternal and neonatal data were compared between groups with an intent-to-treat analysis. The primary outcomes were the latency time to delivery and the incidence of chorioamnionitis. The trial was conducted in a tertiary center of the Portuguese national healthcare system. Patients received standard antibiotic prophylaxis. Delivery was planned for the 34th week of gestation, except in cases of spontaneous labor or another complication. RESULTS: Thirty-two cases were randomized and analyzed, 14 in the complete bed rest group and 18 in the activity restriction group. The median gestational age at PPROM was 30 vs 29 weeks (p = 0.82). In the complete bed rest group, the incidence of chorioamnionitis was nonsignificantly lower (14% vs 28%, p = 0.43). Median latency time was 11.5 days (95% CI, 2-20) in the complete bed rest group and 7.5 days (95% CI, 3-11) in the activity restriction group, lacking statistical significance on univariate (p = 0.6) and survival analyses (log-rank test, p = 0.75). No difference was found between groups regarding indication or type of delivery and maternal or neonatal morbidity. The median gestational age at delivery was 32 weeks for both groups (p = 0.94). A sample size of 2052 participants was calculated for a powered RCT, considering latency as the primary outcome. CONCLUSION: In this pilot trial, bed rest did not increase latency to delivery and did not improve maternal or neonatal morbidity in the setting of PPROM at 24 + 0-33 + 6 weeks. A sample size calculation is now available for a powered RCT.

Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF).

In France, the frequency of premature rupture of the membranes (PROM) is 2%-3% before 37 weeks' gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing enterocolitis (LE2). The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1 are recommended in cases of uncertainty (professional consensus). Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1). Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days (Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is negative (professional consensus). The following are not recommended for antibiotic prophylaxis: amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-generation cephalosporins, clindamycin, or metronidazole (professional consensus). Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home (professional consensus). Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection (professional consensus). No guidelines can be issued about the frequency of this monitoring (professional consensus). Adequate evidence does not exist to support a recommendation for or against the routine initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional consensus). In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the standard obstetric indications (professional consensus). Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with PPROM (professional consensus).