Fetal inflammatory response at the fetomaternal interface: A requirement for labor at term and preterm.

Human parturition at term and preterm is an inflammatory process synchronously executed by both fetomaternal tissues to transition them from a quiescent state t an active state of labor to ensure delivery. The initiators of the inflammatory signaling mechanism can be both maternal and fetal. The placental (fetal)-maternal immune and endocrine mediated homeostatic imbalances and inflammation are well reported. However, the fetal inflammatory response (FIR) theories initiated by the fetal membranes (amniochorion) at the choriodecidual interface are not well established. Although immune cell migration, activation, and production of proparturition cytokines to the fetal membranes are reported, cellular level events that can generate a unique set of inflammation are not well discussed. This review discusses derangements to fetal membrane cells (physiologically and pathologically at term and preterm, respectively) in response to both endogenous and exogenous factors to generate inflammatory signals. In addition, the mechanisms of inflammatory signal propagation (fetal signaling of parturition) and how these signals cause immune imbalances at the choriodecidual interface are discussed. In addition to maternal inflammation, this review projects FIR as an additional mediator of inflammatory overload required to promote parturition.

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.

Adverse live-born pregnancy outcomes among pregnant people with anorexia nervosa.

BACKGROUND: Previous findings related to the association of adverse pregnancy outcomes with anorexia nervosa are mixed. OBJECTIVE: This study aimed to investigate the association of adverse live-born pregnancy outcomes with anorexia nervosa using adjustment modeling accounting for confounding factors, and a mediation analysis addressing the contribution of underweight prepregnancy body mass index and gestational weight gain to those outcomes. STUDY DESIGN: The sample included California live-born singletons with births between 2007 and 2021. The administrative data set contained birth certificates linked to hospital discharge records. Anorexia nervosa diagnosis during pregnancy was obtained from International Classification of Diseases codes on hospital discharge records. Adverse pregnancy outcomes examined included gestational diabetes, gestational hypertension, preeclampsia, anemia, antepartum hemorrhage, premature rupture of membranes, premature labor, cesarean delivery, oligohydramnios, placenta previa, chorioamnionitis, placental abruption, severe maternal morbidity, small for gestational age, large for gestational age, low birthweight, and preterm birth (by timing and indication). Risk of each adverse outcome was calculated using Poisson regression models. Unadjusted risk of each adverse outcome was calculated, and then the risks were adjusted for demographic factors. The final adjusted model included demographic factors, anxiety, depression, substance use, and smoking. A mediation analysis was performed to estimate the excess risk of adverse outcomes mediated by underweight prepregnancy body mass index and gestational weight gain below the American College of Obstetricians and Gynecologists recommendation. RESULTS: The sample included 241 pregnant people with a diagnosis of anorexia nervosa and 6,418,236 pregnant people without an eating disorder diagnosis. An anorexia nervosa diagnosis during pregnancy was associated with many adverse pregnancy outcomes in unadjusted models (relative risks ranged from 1.65 [preeclampsia] to 3.56 [antepartum hemorrhage]) in comparison with people without an eating disorder diagnosis. In the final adjusted models, birthing people with an anorexia nervosa diagnosis were more likely to have anemia, preterm labor, oligohydramnios, severe maternal morbidity, a small for gestational age or low-birthweight infant, and preterm birth between 32 and 36 weeks with spontaneous preterm labor (adjusted relative risks ranged from 1.43 to 2.55). Underweight prepregnancy body mass index mediated 7.78% of the excess in preterm births and 18.00% of the excess in small for gestational age infants. Gestational weight gain below the recommendation mediated 38.89% of the excess in preterm births and 40.44% of the excess in low-birthweight infants. CONCLUSION: Anorexia nervosa diagnosis during pregnancy was associated with a number of clinically important adverse pregnancy outcomes in comparison with people without an eating disorder diagnosis. Adjusting for anxiety, depression, substance use, and smoking during pregnancy decreased this risk. A substantial percentage of the excess risk of adverse outcomes was mediated by an underweight prepregnancy body mass index, and an even larger proportion of excess risk was mediated by gestational weight gain below the recommendation. This information is important for clinicians to consider when caring for patients with anorexia nervosa. Considering and treating anorexia nervosa and comorbid conditions and counseling patients about mediating factors such as preconception weight and gestational weight gain may improve live-born pregnancy outcomes among people with anorexia nervosa.

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.

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.

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.

Endometriosis and preterm birth: A Danish cohort study.

INTRODUCTION: Emerging evidence shows that women with endometriosis face a higher risk of preterm birth. However, the pathways are unclear. The objective of this study is to further investigate at different gestational ages the association between endometriosis and different pathways of preterm birth including, medically indicated preterm birth, premature pre-labor rupture of membranes (PPROM), and spontaneous labor contractions. MATERIAL AND METHODS: In this population-based cohort study we linked singleton pregnancies from the Aarhus Birth Cohort to the Danish National Patient Registry, the Danish Medical Birth Registry, the Danish National Pathology Registry and Data Bank, and the Danish in vitro fertilization registry to gather information on endometriosis status, outcomes and maternal characteristics. We investigated preterm birth before 37 completed weeks of gestation and very preterm birth before 32 completed weeks of gestation. We explored different pathways including medically indicated preterm birth defined as induction of labor with intact membranes and no prior labor contractions, PPROM defined as rupture of membranes, and spontaneous labor contractions defined as contractions with intact membranes resulting in labor. RESULTS: We found that women with endometriosis had an increased risk of preterm birth before 37 gestational weeks overall (adjusted hazard rate [aHR] 1.6, 95% confidence interval [CI] 1.3-1.9) and very preterm birth before 32 gestational weeks (aHR 1.8, 95% CI 1.1-2.9) compared with women without endometriosis. Medically indicated preterm birth was more prominent in women with endometriosis in deliveries before 37 gestational weeks (aHR 2.4, 95% CI 1.8-3.2) whereas spontaneous labor contractions were more common before 32 gestational weeks (aHR 2.2, 95% CI 1.1-4.5) in women with endometriosis compared with women without endometriosis. Further, in the analyses restricted to women with a histologically verified diagnosis of endometriosis, the results were strengthened overall and showed that women with endometriosis had an increased risk of PPROM before 32 gestational weeks (aHR 3.49, 95% CI1.36-8.98). CONCLUSIONS: Endometriosis was associated with both preterm and very preterm birth; however, apparently through different pathways. Women with endometriosis were more prone to have medically indicated preterm births before 37 gestational weeks and spontaneous preterm births before 32 gestational weeks compared with women without endometriosis.

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.

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.

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 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.

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.

Spontaneous hypocarbia without mechanical ventilation in preterm infants with cystic periventricular leukomalacia.

AIM: Hypocarbia induced by mechanical ventilation has been considered a main cause of cystic periventricular leukomalacia (cPVL). However, hypocarbia may occur spontaneously in response to intracellular metabolic acidosis. We aimed to assess whether hypocarbia is more common during mechanical respiratory support than during spontaneous ventilation in infants with cPVL. METHOD: In this single-centre, retrospective chart analysis, we compared partial pressure of carbon dioxide (pCO2 ) during the first 96 hours of life in infants with cPVL during endotracheal mechanical ventilation, non-invasive respiratory support, or without respiratory support. RESULTS: Cystic periventricular leukomalacia was diagnosed in 23 infants born between 2006 and 2017. Gestational age was 24 weeks in two infants and ranged between 28 and 32 weeks in 21 infants. In these 21 infants, pCO2 less than 35 mm Hg during the first 96 ours of life accounted for 9/60 (15%) measurements during endotracheal mechanical ventilation, 16/116 (14%) during non-invasive respiratory support and 14/42 (33%) in infants without respiratory support (P = .014). CONCLUSION: In our series of infants with cPVL, hypocarbia was more common without respiratory support than during endotracheal mechanical ventilation and non-invasive respiratory support. This would suggest that hypocarbia is a symptom rather than a cause of cPVL in these infants.

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 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.

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.

Maternal HBsAg carriers and adverse pregnancy outcomes: A hospital-based prospective cohort analysis.

It is not clear whether chronic hepatitis B virus (HBV) infection during pregnancy can increase the risk of adverse pregnancy outcomes for both mothers and neonates. We conducted a hospital-based prospective cohort study on pregnant women (PW) and used an analysis strategy that was guided by directed acyclic graphs (DAGs). Maternal characteristics and major adverse pregnancy outcomes were collected both from questionnaires and hospital-based electronic medical records. Serum hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) status were determined. In total, 3329 of the 3416 pregnant women who received routine antenatal care in a hospital setting at baseline, including 346 HBsAg carriers, were available for analysis. Maternal HBsAg carrier status was associated with an increased risk of intrahepatic cholestasis pregnancy [aOR (adjusting odds ratio) = 1.70; 95% CI (confidence interval) = 1.16-2.49], premature rupture of the membranes (aOR = 1.38; 95% CI = 1.00-1.89) and large for gestational age birth aOR = 1.67; 95% CI = 1.17-2.39). The risk of intrahepatic cholestasis remained in pregnant women with either HBeAg-positive (aOR = 2.96; 95% CI = 1.33-6.62) or HBeAg-negative (aOR = 1.52; 95% CI =1.00-2.32)] status; notably, only maternal HBeAg-negative status was associated with a higher risk of large for gestational age birth (aOR = 1.91; 95% CI = 1.33-2.76). Our results implied that chronic HBV infection during pregnancy may increase the risk of intrahepatic cholestasis of pregnancy, premature rupture of membranes and large for gestational age pregnancies.

Vaginal Ureaplasma species increase chorioamnionitis in very preterm infants with preterm premature rupture of the membranes at < 28 weeks of gestation.

Our aim was to investigate the association between vaginal Ureaplasma species (spp.) and the subsequent occurrence of chorioamnionitis (CAM), perinatal death, neonatal morbidity, and long-term neurodevelopmental impairments (NDIs) at 3 years of age. We analyzed 55 pregnant women with singleton pregnancy who had preterm premature rupture of the membranes (pPROM) at < 28+0 weeks of gestation, and delivered between 22+0 and 31+6 weeks at our tertiary hospital in 2007-2016. NDIs were defined as either cerebral palsy or developmental delay evaluated at 1.5 and/or 3 years old. The presence of Ureaplasma spp. and Mycoplasma hominis were evaluated using urea-arginine broth and Mycoplasma PPLO Agar. The presence of Ureaplasma spp. in the vagina was positive in 41%. Vaginal Ureaplasma spp. was a significant risk factor for CAM; however, it was not significantly associated with the occurrence of perinatal death, pulmonary hypoplasia, respiratory distress syndrome, transient tachypnea of the newborn, intraventricular hemorrhage, periventricular leukomalacia, bronchopulmonary dysplasia defined as oxygen required and occasional ventilatory assistance required at week 36 as modified (BPD36), or NDIs. The crude odds ratio (95% confidence interval) of Ureaplasma spp. for the occurrence of CAM was 9.5 (1.10-82) (p = 0.041). In very preterm birth infants with pPROM, CAM, BPD36, and NDIs occurred in 78, 60, and 36%, respectively. Vaginal Ureaplasma spp. was a significant risk factor for CAM in very preterm birth infants with pPROM. The incidences of BPD36 and NDIs in such infants were very high, nearing 3/5 and 1/3, respectively.

Management of Group B Streptococcus-Positive Women With Preterm Premature Rupture of the Membranes: Still a Therapeutic Dilemma.

We discuss the management of GBS positive women with PPROM, an aspect of obstetrical management that remains controversial despite the publication of new randomized control trials in recent years. Clinical practice guidelines from several countries' national organizations are compared and contrasted, and areas of uncertainty are identified.

Association of histological chorioamnionitis and magnesium sulfate treatment in singleton and dichorionic twin pregnancies with preterm premature rupture of membranes: preliminary observations.

Objective To evaluate the possible association between antenatal magnesium sulfate treatment with histological chorioamnionitis in patients with singleton or dichorionic twins that had preterm premature rupture of the membranes. Methods This was an observational study performed in patients admitted to the hospital with rupture of membranes before 34 weeks' gestation. The primary outcome was histological chorioamnionitis and the primary predictor was antenatal magnesium sulfate treatment. A logistic regression model was used without consideration of other antenatal medical treatments. Results Among 107 patients with preterm deliveries, 57 were admitted to the hospital before 34 weeks' gestation with preterm premature rupture of membranes. Fifty-cases were excluded from the analysis because they were admitted after 34 weeks' gestation, delivered before 24 weeks' gestation or had intrauterine fetal demise or monochorionic twins. The logistic regression analysis adjusting for maternal age, gravidity, parity, multiple gestation, gestational age at delivery, and birthweight, indicated that patients with singleton pregnancies and histological chorioamnionitis had received magnesium sulfate antenatally more frequently (χ2=6.46; P=0.01). The association between histological chorioamnionitis and magnesium sulfate treatment was not found among patients with dichorionic twin pregnancies with one intact gestational sac. Conclusions In this cohort of patients with preterm premature rupture of membranes admitted to the hospital before 34 week's gestation, those with singleton pregnancies treated antenatally with magnesium sulfate for neonatal neuroprotection had a greater rate of histological chorioamnionitis.