Semi-quantitative metalloproteinase-8 rapid test for the prediction of adverse pregnancy outcomes in patients with preterm premature rupture of membranes.

OBJECTIVE: We aimed to determine whether the semi-quantitative metalloproteinase-8 (MMP-8) bedside test is a worthwhile indicator in reflecting the severity of of intra-amniotic inflammation (IAI) and in predicting adverse pregnancy outcomes. STUDY DESIGN: This retrospective cohort study comprised 76 singleton-pregnant women admitted to the Seoul National University Bundang Hospital with a diagnosis of preterm premature rupture of membranes (preterm PROM) between 20 weeks 0 days and 33 weeks 6 days of gestation who underwent trans-abdominal amniocentesis to confirm intra-amniotic infection by positive results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma and evaluate lung maturity. The semi-quantitative MMP-8 rapid test kit employs a colourimetric assay to quantify MMP-8 levels in amniotic fluid (AF), expressing results from 0 to 100 percent. Participants were divided into three groups: group 1, including negative MMP-8 test with colour scale of 0 % (negative, n = 17); group 2, including positive MMP-8 test with colour scale < 51 % (weak positive, n = 21); and group 3, including positive MMP-8 test with colour scale of 51 %-100 % (strong positive, n = 38). RESULTS: Approximately 78 % (59/76) of the participants showed a positive MMP-8 test result; all culture-proven AF samples (33.3 % [25/75]) yielded positive MMP-8 test, categorizing these patients into either group 2 or group 3. A significant trend was observed where the rate of positive culture-proven samples increased with the progression from group 1 (negative) to group 3 (strong positive). Both white blood cell counts in AF and maternal serum C-reactive protein levels were found to escalate with the progression of test results from negative to strong positive. This progression was associated with an increased risk of spontaneous preterm birth within 48 h, 7 days, and 14 days from amniocentesis and within 34 weeks of gestation. CONCLUSION: The more the test results progress from negative to strong positive, the shorter the interval from amniocentesis to delivery becomes, and the higher the risk of intra-amniotic infection, spontaneous preterm delivery, and other perinatal complications. This relationship highlights the critical value of the semi-quantitative MMP-8 rapid test in predicting adverse pregnancy outcomes in patients with preterm PROM.

Immersive virtual reality simulation training for cesarean section: a randomized controlled trial.

BACKGROUND: Caesarean section (CS) is a complex surgical procedure that involves many steps and requires careful precision. Virtual reality (VR) simulation has emerged as a promising tool for medical education and training, providing a realistic and immersive environment for learners to practice clinical skills and decision-making. This study aimed to evaluate the educational effectiveness of a VR simulation program in training the management of patients with premature rupture of membranes (PROM) and CS. MATERIALS AND METHODS: A two-arm parallel randomized controlled trial was conducted with 105 eligible participants randomly assigned to the VR group ( n =53) or the control group ( n =52) in a 1:1 ratio. The VR group received VR simulation training focused on PROM management and CS practice, while the control group watched a video presentation with narrative of clinical scenario and recording of CS. Both groups completed questionnaires assessing their prior experiences with VR, experience in managing patients with PROM and performing CS, as well as their confidence levels. These questionnaires were administered before and after the intervention, along with a mini-test quiz. RESULTS: Baseline characteristics and previous experiences were comparable between the two groups. After the intervention, the VR group had higher confidence scores in all four aspects, including managing patients with PROM, performing CS as an operator, and understanding the indications and complications of CS, compared to the control group. The VR group also achieved significantly higher scores on the mini-test quiz [median (interquartile range), 42 (37-48) in the VR group; 36 (32-40) in the control group, P <0.001]. CONCLUSION: VR simulation program can be an effective educational tool for improving participants' knowledge and confidence in managing patients with PROM and performing CS.

Effect of pelvic artery embolization for postpartum hemorrhage on subsequent pregnancies: a single-center retrospective cohort study.

OBJECTIVE: Pelvic artery embolization (PAE) is a uterus-saving treatment for postpartum hemorrhage (PPH); however, subfertility or abnormal placentation for subsequent pregnancy has been a concern in several previous reports. This study aimed to investigate the impact of PAE on subsequent pregnancies in women with a history of PPH. METHODS: A retrospective cohort study was conducted on women transferred to the tertiary center for PPH and delivered for the next pregnancy at the same center later. The study group was divided into two groups based on PAE application to treat previous PPH. RESULTS: Of the 62 women included, 66% (41/62) had received PAE for the previous PPH, while 21 had not. Pregnancy outcomes for subsequent pregnancies were compared between the PAE and non-PAE groups. The PAE group had a higher estimated blood loss volume for the present delivery than the non-PAE group (600 vs. 300 mL, p = 0.008). The PAE group also demonstrated a higher incidence of placenta previa (4.8% vs. 24.4%, p = 0.080) and placenta accreta (0% vs. 14.6%, p = 0.082) than the non-PAE group, although the difference was not statistically significant. CONCLUSION: These findings suggest that the use of PAE to treat PPH may increase the risk of bleeding, placenta previa, and placenta accreta spectrum in subsequent pregnancies.

Analysis of gastric fluid in preterm newborns supports the view that the amniotic cavity is sterile before the onset of parturition: a retrospective cohort study.

OBJECTIVES: To compare the frequency of Ureaplasma-positive gastric fluid (GF) cultures based on the cause and mode of delivery in preterm newborns. METHODS: This retrospective cohort study included women with a singleton pregnancy who delivered prematurely (between 23+0 and 32+0 weeks of gestation, n=464) at a single university hospital in South Korea. The newborns' GF was obtained on the day of birth via nasogastric intubation. The frequency of Ureaplasma spp. in GF cultures was measured and compared according to the cause and mode of delivery. RESULTS: Ureaplasma spp. was detected in 20.3 % of the GF samples. The presence of Ureaplasma spp. was significantly higher in the spontaneous preterm birth group than in the indicated preterm birth group (30.2 vs. 3.0 %; p<0.001). Additionally, Ureaplasma spp. was more frequently found in the vaginal delivery group than in the cesarean delivery group, irrespective of the cause of preterm delivery [indicated preterm birth group (22.2 vs. 1.9 %, p=0.023); spontaneous preterm birth group (37.7 vs. 24.2 %, p=0.015)]. CONCLUSIONS: Ureaplasma spp. were found in 20.3 % of the GFs. However, only 1.9 % of newborns in the indicated preterm birth group with cesarean delivery had a Ureaplasma-positive GF culture.

Factors Associated with Spontaneous Preterm Birth after Ultrasound-Indicated Cerclage.

Ultrasound-indicated cerclage (UIC) is recommended to prevent spontaneous preterm birth (sPTB) in women with a short cervix at mid-trimester and a history of PTB. We assessed the factors related to sPTB after UIC and determined the corresponding risks. This retrospective cohort study was conducted at a university hospital. UIC was performed between 15 and 26 weeks of gestation in women with a cervical length of <2.5 cm. Univariate and multivariate analyses were used to examine factors associated with sPTB after UIC. An earlier gestational age and shorter cervical length at UIC were associated with sPTB after UIC. While PTB history was not associated with an increased risk of sPTB, it did increase the risk of repeat cerclage after UIC. Higher levels of preoperative serum inflammatory markers and obesity significantly increased the risk of sPTB after UIC. These findings provide helpful guidance for patient counseling and management in predicting the delivery timing after UIC in women with a short cervix in the mid-trimester.

Neonatal outcomes of early preterm births according to the delivery indications.

OBJECTIVE: To compare the neonatal outcomes of early preterm births according to delivery indications and determine the obstetric risk factors associated with adverse outcomes. METHODS: We retrospectively studied pregnancies delivered between 22 + 0 and 26 + 6 weeks at the tertiary center between April 2013 and April 2022. Stillbirths, elective termination of pregnancy, and multifetal pregnancies were excluded. Patients were classified into two groups according to delivery indications: spontaneous preterm birth (sPTB) due to premature rupture of membranes (PROM), preterm labor, or acute cervical insufficiency; and indicated preterm birth (iPTB). Obstetric and neonatal outcomes were compared between the groups. RESULTS: Of the 121 neonates, 73 % (88/121) underwent sPTB. The overall survival rates were 73 % and 49 % in the sPTB and iPTB groups, respectively (p = 0.017). Multivariate logistic regression analysis was performed with adjustment for gestational age at delivery, fetal growth restriction, cesarean section, histological chorioamnionitis, and funisitis. Moreover, in the 1-year follow-up, the proportion of body mass below the third percentile was significantly higher in the iPTB-group than in the sPTB-group (53 % vs. 20 %, p = 0.019). Furthermore, diagnoses of developmental delay and cerebral palsy were slightly higher in the iPTB-group (33 % and 20 %, respectively) than in the sPTB-group (27 % and 9 %, respectively); however, this difference was not statistically significant. CONCLUSIONS: In early preterm births, iPTB was associated with a higher neonatal mortality than sPTB.

Danazol as a Treatment for Uterine Arteriovenous Malformation: A Case Report.

Uterine arteriovenous malformation (AVM) is associated with a risk of massive uterine bleeding. Although uterine artery embolization remains the first-line treatment for AVM, there has been a recent exploration of pharmacological options. Danazol is known to reduce blood flow to the uterus; however, our understanding of its therapeutic efficacy for AVM remains limited. Herein, we present the results of danazol use in patients with uterine AVM. We retrospectively reviewed the medical records of patients who received danazol for the treatment of AVM between January 2013 and November 2022. The cohort comprised 10 patients who developed AVM after dilatation and curettage (D&C), abortion, or cesarean section. Danazol was administered twice daily at a total dose of 400 mg/day, and was employed for AVM treatment in hemodynamically stable patients who provided consent and were devoid of massive bleeding. Outpatient follow-ups (ultrasound measurements of AVM size and symptom assessment) were performed every 2 weeks. AVM was successfully treated with danazol in most patients with no adverse event. Eight postabortal patients had complete resolution of AVM after an average of 45 days (range 14-70 days). Of two patients who developed AVM after a cesarean section, one experienced AVM reduction, and the other developed massive bleeding, requiring emergency uterine artery embolization. In light of these outcomes, danazol can be potentially prioritized over uterine artery embolization in the treatment of AVM after abortion in hemodynamically stable patients.

Cytomegalovirus infection during pregnancy.

Cytomegalovirus (CMV) infection during pregnancy is a global silent problem. Additionally, it is the leading cause of congenital infections, non-genetic sensorineural hearing loss, and neurodevelopmental delays in infants. However, this has barely been recognized globally. This condition lacks adequate attention, which is further emphasized by the lack of awareness among healthcare workers and the general population. The impact of CMV infection is often overlooked because of the asymptomatic nature of its presentation in infected pregnant women and newborns, difficulty in diagnosis, and the perception that infants born to women with pre-existing antibodies against CMV have normal neonatal outcomes. This article highlights the latest information on the epidemiology, transmission, clinical manifestations, and development of CMV infection and its management. We reviewed the pathophysiology and clinical manifestations of CMV infection in pregnant women, diagnostic methods, including screening and prognostic markers, and updates in treatment modalities. Current advancements in research on vaccination and hyperimmunoglobulins with worldwide treatment protocols are highlighted.

Inflammatory biomarkers in the cervicovaginal fluid to identify histologic chorioamnionitis and funisitis in women with preterm labor.

OBJECTIVE: We investigated the association between altered levels of inflammatory proteins in the cervicovaginal fluid (CVF) and acute histologic chorioamnionitis (HCA) and funisitis in women with preterm labor (PTL). METHODS: In this study, a total of 134 consecutive singleton pregnant women with PTL (at 23+0-34+0 weeks) who delivered preterm (at  < 37 weeks) and from whom CVF samples were collected at admission were retrospectively enrolled. The CVF levels of haptoglobin, interleukin-6/8, kallistatin, lipocalin-2, matrix metalloproteinase (MMP)-8, resistin, S100 calcium-binding protein A8, and serpin A1 were determined using enzyme-linked immunosorbent assay. The placentas were histologically analyzed after delivery. RESULTS: Multiple logistic regression analyses showed significant associations between elevated CVF interleukin-8 and resistin levels and acute HCA after adjusting for baseline covariates (e.g., gestational age at sampling). CVF haptoglobin, interleukin-6/8, kallistatin, MMP-8, and resistin levels were significantly higher in women with funisitis than in those without, whereas the baseline covariates were similar between the two groups (P > 0.1). The area under the receiver operating characteristic curves of the aforementioned biomarkers ranged from 0.61 to 0.77 regarding each outcome. Notably, HCA risk significantly increased with increasing CVF levels of interleukin-8 and resistin (P for trend  < 0.05). CONCLUSIONS: Haptoglobin, interleukin-6/8, kallistatin, MMP-8, and resistin were identified as potential inflammatory CVF biomarkers predictive of acute HCA and funisitis in women with PTL. Moreover, the risk severity of acute HCA may be associated with the degree of the inflammatory response in the CVF (particularly based on interleukin-8 levels).

Degree of expression of inflammatory proteins in the amniotic cavity, but not prior obstetric history, is associated with the risk severity for spontaneous preterm birth after rescue cerclage for cervical insufficiency.

PROBLEM: To examine whether the severity of spontaneous preterm birth (SPTB) risk after rescue cerclage for acute cervical insufficiency (CI) is linked to the degree of inflammatory response in the amniotic fluid (AF) based on the concentrations of various inflammatory proteins and prior obstetric history. METHOD OF STUDY: We conducted a retrospective cohort study of 65 singleton pregnant women (17-25 weeks) who underwent rescue cerclage following the diagnosis of acute CI and were subjected to amniocentesis. EN-RAGE, IL-6, IL-8, and IP-10 as inflammatory mediators and kallistatin, MMP-2/8, and uPA as extracellular matrix remodeling-related molecules were assayed in the AF using ELISA. The level of each inflammatory mediator was divided into quartiles. RESULTS: Intra-amniotic inflammation (IAI; AF IL-6 level ≥2.6 ng/mL) was independently associated with SPTB after cerclage placement. The odds of SPTB at < 32 weeks, even after adjusting for confounders, increased significantly with each increasing quartile of baseline AF levels for each inflammatory mediator (p for trend < .05). Kaplan-Meier survival curves showed that the cerclage-to-delivery intervals were significantly shorter as the quartiles of AF EN-RAGE and MMP-8 increased (log-rank test, p < .01 each). Neither previous term birth nor prior PTB was associated with SPTB risk or cerclage-to-delivery interval after rescue cerclage. Multiparous women who experience CI after term birth showed significantly elevated levels of MMP-8 and reduced kallistatin levels in the AF. CONCLUSION: In patients with CI, SPTB risk (especially risk severity) after rescue cerclage is associated with the degree of the inflammatory response in AF as well as the presence of IAI but not with prior obstetric history.

Extracellular matrix-related and serine protease proteins in the amniotic fluid of women with early preterm labor: Association with spontaneous preterm birth, intra-amniotic inflammation, and microbial invasion of the amniotic cavity.

PROBLEM: We aimed to determine whether altered levels of various extracellular matrix (ECM)-related and serine protease proteins in the amniotic fluid (AF) are associated with imminent spontaneous preterm birth (SPTB; ≤7 days) and intra-amniotic inflammation and/or microbial invasion of the amniotic cavity (IAI/MIAC) in women with early preterm labor (PTL). METHOD OF STUDY: This retrospective cohort study included 252 women with singleton pregnancies undergoing transabdominal amniocentesis who demonstrated PTL (24-31 weeks). The AF was cultured for microorganism detection to characterize MIAC. IL-6 concentrations were determined in the AF samples to identify IAI (≥2.6 ng/mL). The following mediators were measured in the AF samples using ELISA: kallistatin, lumican, MMP-2, SPARC, TGFBI, and uPA. RESULTS: Kallistatin, MMP-2, TGFBI, and uPA levels were significantly higher and SPARC and lumican levels were significantly lower in the AF of women who spontaneously delivered within 7 days than in the AF of those who delivered after 7 days; the levels of the first five mediators were independent of baseline clinical variables. In the multivariate analysis, elevated levels of kallistatin, MMP-2, TGFBI, and uPA and low levels of lumican and SPARC in the AF were significantly associated with IAI/MIAC and MIAC, even after adjusting for the gestational age at sampling. The areas under the curves of the aforementioned biomarkers ranged from 0.58 to 0.87 for the diagnoses of each of the corresponding endpoints. CONCLUSION: ECM-related (SPARC, TGFBI, lumican, and MMP-2) and serine protease (kallistatin and uPA) proteins in the AF are involved in preterm parturition and regulation of intra-amniotic inflammatory/infectious responses in PTL.

Proteomic analysis of plasma to identify novel biomarkers for intra-amniotic infection and/or inflammation in preterm premature rupture of membranes.

To identify potential plasma biomarkers associated with microbial invasion of the amniotic cavity (MIAC) and/or intraamniotic inflammation (IAI) in women with preterm premature rupture of membranes (PPROM). This retrospective cohort study included 182 singleton pregnant women with PPROM (23-33 weeks) who underwent amniocentesis. Plasma samples; all subjects were chosen from these participants and were analyzed using label-free liquid chromatography-tandem mass spectrometry for proteome profiling using a nested case-control study design (cases with MIAC/IAI vs. non-MIAC/IAI controls [n = 9 each]). Three identified target molecules for MIAC/IAI were further verified by ELISA in the study cohort (n = 182). Shotgun proteomic analysis revealed 17 differentially expressed proteins (P < 0.05) in the plasma of MIAC/IAI cases. In particular, the levels of FCGR3A and haptoglobin, but not LRP1, were found to be increased in the plasma of patients with MIAC, IAI, and both MIAC/IAI compared with those without these conditions. Moreover, these differences remained significant after adjusting for gestational age at sampling. The area under the curves of plasma FCGR3A and haptoglobin ranged within 0.59-0.65 with respect to each of the three outcome measures. Plasma FCGR3A and haptoglobin were identified as potential independent biomarkers for less-invasively detecting MIAC/IAI in women with PPROM.

Cord blood transforming growth factor-ß-induced as predictive biomarker of retinopathy of prematurity in preterm infants.

PURPOSE: To determine whether 14 inflammation-, angiogenesis-, and adhesion-related proteins in cord blood (CB), alone or in combination with conventional perinatal factors, could predict retinopathy of prematurity (ROP) in preterm infants. METHODS: Data from 111 preterm infants (born at ≤ 32.0 weeks) were retrospectively reviewed. The levels of endoglin, E-selectin, HSP70, IGFBP-3/4, LBP, lipocaline-2, M-CSFR, MIP-1α, pentraxin 3, P-selectin, TGFBI, TGF-ß1, and TNFR2 were assessed in stored CB samples collected at birth using ELISA kits. The primary endpoints included severe ROP (≥ stage 3) and type 1 ROP requiring treatment. RESULTS: ROP was diagnosed in 29 infants (26.1%), among whom 14 (12.6%) had severe ROP and seven (6.3%) had type 1 ROP. Multivariate logistic regression showed that decreased CB TGFBI levels were significantly associated with severe ROP and type 1 ROP after adjusting for gestational age at birth. Stepwise regression analysis allowed to design prediction models with good accuracy, which comprised low CB TGFBI levels and low birth weight (BW) as predictors for severe ROP (area under the curve [AUC] = 0.888), and low CB endoglin levels and low BW as predictors for type 1 ROP (AUC = 0.950). None of the other CB proteins evaluated were found to be associated with severe ROP or type 1 ROP. CONCLUSIONS: Low CB TGFBI levels are associated with severe ROP and type 1 ROP, independently of gestational age. Moreover, combined predictive models based on CB TGFBI and endoglin levels, along with BW data, may act as good indicators at birth for the neonatal risk of ROP progression.

Expression of inflammatory, angiogenic, and extracellular matrix-related mediators in the cervicovaginal fluid of women with preterm premature rupture of membranes: Relationship with acute histological chorioamnionitis.

PROBLEM: To investigate whether altered expression of various inflammation-, angiogenesis-, and extracellular matrix-related mediators in cervicovaginal fluid (CVF) could be independently associated with acute histological chorioamnionitis (HCA), microbial-associated HCA, and funisitis in women with preterm premature rupture of membranes (PPROM). METHOD OF STUDY: Clinical data of 102 consecutive singleton pregnant women with PPROM at 23+0 to 34+0 weeks were retrospectively analyzed. CVF samples were collected upon admission. Levels of APRIL, DKK-3, IGFBP-1/2, IL-6/8, lipocalin-2, M-CSF, MIP-1α, MMP-8/9, S100A8A9, TGFBI, TIMP-1, TNFR2, uPA, and VDBP were determined by ELISA. Placentas were histologically examined after birth. RESULTS: Multivariate logistic regression analyses showed that: (1) elevated CVF levels of IL-8 and TNFR2 were independently associated with acute HCA; (2) elevated CVF levels of IL-6, IL-8, M-CSF, MMP-8, and TNFR2 were independently associated with microbial-associated HCA; and (3) elevated CVF IL-8 and MMP-8 levels were independently associated with funisitis when adjusted for gestational age. Areas under the curves of the aforementioned CVF biomarkers ranged within 0.61-0.77, thereby demonstrating poor to fair diagnostic capacity for these clinical endpoints. HCA risk significantly increased as the CVF levels of each inflammatory mediator increased (P for trend < 0.05). CONCLUSIONS: Herein, we identified several inflammatory biomarkers (IL-6/8, M-CSF, MMP-8, and TNFR2) in the CVF that are independently associated with acute HCA, microbial-associated HCA, and funisitis in women with PPROM. Furthermore, the degree of inflammatory response in the CVF, based on the levels of these proteins, demonstrated a direct relationship with HCA risk (especially risk severity).

Effects of Fetal Images Produced in Virtual Reality on Maternal-Fetal Attachment: Randomized Controlled Trial.

BACKGROUND: Maternal-fetal attachment (MFA) has been reported to be associated with the postpartum mother-infant relationship. Seeing the fetus through ultrasound might influence MFA, and the effect could be increased by more realistic images, such as those generated in virtual reality (VR). OBJECTIVE: The aim was to determine the effect of fetal images generated in VR on MFA and depressive symptoms through a prenatal-coaching mobile app. METHODS: This 2-arm parallel randomized controlled trial involved a total of 80 pregnant women. Eligible women were randomly assigned to either a mobile app-only group (n=40) or an app plus VR group (n=40). The VR group experienced their own baby's images generated in VR based on images obtained from fetal ultrasonography. The prenatal-coaching mobile app recommended health behavior for the pregnant women according to gestational age, provided feedback on entered data for maternal weight, blood pressure, and glucose levels, and included a private diary service for fetal ultrasound images. Both groups received the same app, but the VR group also viewed fetal images produced in VR; these images were stored in the app. All participants filled out questionnaires to assess MFA, depressive symptoms, and other basic medical information. The questionnaires were filled out again after the interventions. RESULTS: Basic demographic data were comparable between the 2 groups. Most of the assessments showed comparable results for the 2 groups, but the mean score to assess interaction with the fetus was significantly higher for the VR group than the control group (0.4 vs 0.1, P=.004). The proportion of participants with an increased score for this category after the intervention was significantly higher in the VR group than the control group (43% vs 13%, P=.005). The feedback questionnaire revealed that scores for the degree of perception of fetal appearance all increased after the intervention in the VR group. CONCLUSIONS: The use of a mobile app with fetal images in VR significantly increased maternal interaction with the fetus. TRIAL REGISTRATION: ClinicalTrials.gov NCT04942197; https://clinicaltrials.gov/ct2/show/NCT04942197.

The Point-Of-Care Test to Detect Nephrin from Urine in Preeclampsia.

BACKGROUND: Nephrin is a protein in the glomerular podocyte slit diaphragm; therefore, its presence in urine implies damage to podocytes. This study aimed to determine the usefulness of nephrin as a biomarker in maternal urine to predict preeclampsia (PE). METHODS: This prospective study included pregnant women admitted for delivery at Seoul National University Bundang Hospital from March 2019 to May 2020. Patients who had been diagnosed with PE were included, and patients without a history of underlying diseases were recruited for the control group. Pertinent clinical data were collected. Urine samples were obtained, and nephrin signaling was detected through test strips using a lateral flow assay. The point-of-care test results were compared between patients with PE and without (control group), using the exact concentration of nephrin by enzyme-linked immunosorbent assay. RESULTS: Clinical characteristics - maternal age, parity, proportion of twin pregnancies, height, weight, and cesarean delivery rate - were comparable between the PE and control groups. Nephrin signals were classified into four groups. In the PE group, signals 0, 1, 2, and 3 were found in 18.4% (9/49), 44.9% (22/49), 24.5% (12/49), and 12.2% (6/49) of participants, respectively. Results were significantly different in the control group, in which 84.3% (43/51) were found to have signal 0 (p < 0.001). CONCLUSIONS: Nephrin signaling in maternal urine could be a noninvasive and useful test for early detection of severity of PE.

Plasma IGFBP-1, Fas, kallistatin, and P-selectin as predictive biomarkers of histologic chorioamnionitis and associated intra-amniotic infection in women with preterm labor.

PROBLEM: To determine whether altered levels of 13 plasma biomarkers, alone or in combination, could be independently associated with histologic chorioamnionitis (HCA) and microbial-associated HCA (defined as the presence of HCA along with microbial invasion) in women with preterm labor (PTL). METHODS OF STUDY: This was a retrospective cohort study involving 77 singleton pregnant women with PTL (23-34 gestational weeks) who delivered within 96 h of plasma and amniotic fluid (AF) sampling. DKK-3, E-selectin, Fas, haptoglobin, IGFBP-1, kallistatin, MMP-2, MMP-8, pentraxin 3, progranulin, P-selectin, SAA4, and TGFBI levels were assayed in plasma samples by ELISA. AF obtained via amniocentesis was used for microorganism identification. RESULTS: Multiple logistic regression analyses revealed significant associations between low plasma IGFBP-1 levels and acute HCA, and between low plasma Fas and kallistatin levels, and elevated plasma P-selectin levels and microbial-associated HCA (all p < .05), after adjusting for gestational age. Using a stepwise regression procedure, a multi-biomarker panel for microbial-associated HCA was developed, which included plasma MMP-2, kallistatin, and P-selectin levels (area under the curve [AUC], .867). The AUC for this three-marker panel was significantly or borderline significantly greater than that of any single variable included in the panel. However, a predictive model for acute HCA could not be developed because only one variable (MMP-2) was selected. CONCLUSIONS: These findings demonstrate that IGFBP-1, Fas, kallistatin, and P-selectin are associated with acute HCA and microbial-associated HCA in women with PTL. Their combined use can significantly improve the diagnostic ability for the detection of microbial-associated HCA.

A Comparison of Ultrasound Imaging Texture Analyses During the Early Postpartum With the Mode of Delivery.

BACKGROUND: Breastfeeding is beneficial to infants. However, cesarean section is reported to be a risk factor for unsuccessful breastfeeding. RESEARCH AIMS: (1) To extract discriminating data from texture analysis of breast ultrasound images in the immediate postpartum period; and (2) to compare the analysis results according to delivery mode. METHODS: A cross-sectional, prospective non-experimental design with a questionnaire and observational components was used. Participants (N = 30) were women who delivered neonates at a center from September 2020 to December 2020. The participants underwent ultrasound examination of bilateral breasts 7-14 days after delivery. Ultrasound images were collected for texture analysis. A questionnaire about breastfeeding patterns was given to the participants on the day of the ultrasound examination. RESULTS: No significant differences were found in texture analysis between the breasts of participants who had undergone Cesarean section and vaginal deliveries. The mean volume of total human milk produced in 1 day was significantly greater in the vaginal delivery group than in the cesarean section group (M = 350.87 ml, SD = 183.83 vs. M = 186.20 ml, SD = 184.02; p = .017). The pain score due to breast engorgement measured subjectively by participants was significantly lower in the vaginal delivery group than in the cesarean section group (M = 2.8, SD = 0.86 vs. M = 3.4, SD = 0.63; p = .047). CONCLUSION: Texture analysis of breast ultrasound images did not demonstrate difference between the cesarean section and vaginal delivery groups in the immediate postpartum period; nevertheless, cesarean section was independently associated with less successful breastfeeding.

Association of inflammatory and angiogenic biomarkers in maternal plasma with retinopathy of prematurity in preterm infants.

OBJECTIVE: To investigate whether various novel inflammatory and angiogenic biomarkers in maternal plasma, alone or in combination with baseline antenatal factors, could predict retinopathy of prematurity (ROP) in preterm infants. METHODS: A retrospective cohort study was conducted on 140 premature singleton neonates born to women with preterm birth (≤32 weeks) and screened for ROP. Maternal blood obtained at the time of admission was assayed for CRP, endoglin, endostatin, IGFBP-2, IGFBP-3, IL-6, LBP, MMP-8, PlGF, S100A8/A9, TGFBI, and VEGFR-1. The primary outcome measures included severe ROP (stage 3 or higher) and type 1 ROP requiring treatment. RESULTS: ROP was present in 25.7% (36/140) of the study population, including 20 (14.3%) cases of severe ROP and 14 (10%) with type 1 ROP. Multiple logistic regression analyses revealed significant associations between high concentrations of maternal plasma LBP and severe ROP, and between elevated plasma IL-6 and LBP levels and type 1 ROP (all P < 0.05), while adjusting for confounders (i.e., gestational age [GA] at sampling). Prenatal prediction models for severe ROP and type 1 ROP were developed by combining plasma IL-6 or LBP levels with GA at sampling, which showed good discriminatory power (area under the curve = 0.747 and 0.854, respectively). CONCLUSIONS: IL-6 and LBP in maternal plasma were found to be independently associated with severe ROP and type 1 ROP. Prediction models based on these biomarkers along with GA at sampling may serve as good prenatal indicators for the neonatal risk of ROP progression in women at risk of preterm birth.

Association between in vitro fertilisation embryo transfer and placental pathology in women with preterm birth: a retrospective cohort study.

CONTEXT: The number of women who achieve pregnancy through assisted reproductive technology (ART), including in vitro fertilisation and embryo transfer (IVF-ET), is increasing worldwide. Placenta-mediated diseases associated with ART, such as gestational hypertension, preeclampsia, disorders of placental implantation, and placental abruption, are also increasing. AIMS: To determine the association between placental pathologies and IVF-ET in women with preterm births. METHODS: This retrospective cohort study examined archived placenta specimens of women who achieved pregnancy through either spontaneous conception or IVF-ET. In total, 1677 women with singleton pregnancies who gave birth consecutively between 20 and 37weeks of gestation at Seoul National University Bundang Hospital and underwent placental pathologic evaluation between April 2013 and October 2018 were included. Data from all pathologic reports were reviewed. KEY RESULTS: The IVF-ETgroup had a higher median maternal age and rate of nulliparity than the natural conception group. The incidence rate of obstetric complications, except preterm premature rupture of membranes and placenta previa, was similar in both groups. The IVF-ET group had a higher incidence rate of placental infarction than the natural conception group (26.4% vs 16.4%, P =0.012). Multivariate logistic regression analysis indicated that IVF, hypertensive disorders, and fetal growth restriction were significantly associated with placental infarction. CONCLUSIONS: IVF-ET was independently associated with the risk of placental infarction in women with preterm births. IMPLICATIONS: The use of IVF-ET may cause abnormal placental formation with an increased risk of anatomical and vascular pathology, which are observed in preterm deliveries and may contribute to pregnancy complications.