Anti-infectious and anti-inflammatory effect of amniopatch in the treatment of spontaneous previable rupture of membranes.

Spontaneous previable rupture of membranes complicates approximately 0.4-0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure-volume ratios. The supposed basis of this physical-mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical-academic and publishing outputs of the authors based on their many years' experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008-2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research-academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.

Analysis of factors influencing ultrasound-based fetal weight estimation.

OBJECTIVES: Determining the mean deviation between estimated fetal weight (EFW) measured by ultrasound biometry and the real final birth weight and defining the factors influencing the accuracy of weight estimation. BACKGROUND: Estimated weight of the fetus before birth is valuable information for obstetricians particularlyin choosing the method, management, and timing of delivery. METHODS: The retrospective study analyzed 331 medical records of induced labor between January and June 2021. Fetal weight estimation was calculated using Hadlock formulas. The anamnestic data were obtained from medical records, namely: maternal age, maternal BMI, parity, date of the last ultrasonography (USG) before delivery, fetal presentation, placental location, EFW (including the physician's name performing the measurement, and time of the measurement), gestational age of the fetus, date of birth, fetal gender, neonatal weight and length. The correlations between the weight deviation and other factors were expressed using the Pearson and Phik (Φk) correlation coefficients. The Bland Altman method was used to visualize the correspondence between the two variables. The hypotheses were based on the acquired knowledge and then tested by Mann-Whitney U, Kruskal-Wallis, and ANOVA statistical tests, as required by the hypotheses and input data. RESULTS: The mean EFW in the studied group was 3,459 ± 435 g, and the mean actual birth weight was 3,508 ± 508 g. The mean absolute deviation between monitored weight parameters was 260.27 g. The mean real birth weight was higher compared to EFW by 4.873 g. A significant effect on EFW was observed for the following factors: time interval between sonographic weight estimation and delivery (less than 7 days), high maternal BMI (> 30 kg/m2), maternal age, and neonatal weight and length. The factors of fetal presentation, placental location, amniotic fluid volume, fetal gender, gestational age, parity, or those of examiner did not seem to impact EFW accuracy in our study. CONCLUSION: The time interval between sonographic weight estimation and delivery (shorter than 7 days), maternal BMI over 30 kg/m2, maternal age, neonatal weight and length are all factors significantly associated with the accuracy of ultrasound-based fetal weight estimation (Tab. 2, Ref. 13). Text in PDF www.elis.sk Keywords: ultrasound, biometry, fetal weight estimation.

Amniopatch as an active treatment of spontaneous previable rupture of membranes.

OBJECTIVE: To assess the use of amniopatch - intraamniotic application of maternal platelets and cryoprecipitate, in patients after spontaneous previable rupture of membranes (sPPPROM) in terms of its effect on the course and outcome of pregnancy in the largest cohort so far. Since the amniopatch is currently used only to treat patients with iatrogenic preterm rupture of membranes, aim of this study was to find out, if amniopatch could be also used in case of sPPPROM as a safe alternative to currently used expectant management and to compare the results with published data on expectant management. METHODS: The study included 53 patients with single-fetal pregnancy after sPPPROM who underwent amniopatch as an experimental method in the years 2008-2019. Authors evaluated individual characteristics for the whole group as well as a subgroup of live-born neonates who survived to discharge and abortions/live-born infants who did not survive to discharge. RESULTS: The mean time of sPPPROM was 19 + 3 gestational week (gw) and of amniopatch performance 22 + 0 gw. Across the group, the miscarriage rate was 33.96%, survival rate 66.03%, mortality rate after delivery 8.57%, survival rate to discharge 60.37%. The mean time of latency period was 5 + 3 gw in the total group, 7 + 1 gw in the group of live births who survived to discharge. We did not find any maternal/fetal complications related directly to amniopatch procedure. CONCLUSION: Amniopatch is a safe treatment alternative in patients with sPPPROM who require an active approach. It is associated with high percentage of a success rate in terms of duration of pregnancy and neonatal survival. In order to elucidate the possible mechanism of amniopatch effect in sPPPROM despite failure of complete sealing of membrane defect, authors give novel hypothesis of antimicrobial effect of amniopatch based on literature data.

Is amniopatch an effective treatment for spontaneous previable premature rupture of membranes? Analysis of perinatal outcome.

OBJECTIVES: To characterize the perinatal outcomes of pregnancies complicated by spontaneous previable premature rupture of membranes with a therapeutic intervention in the form of amniopatch (AP) at the 2nd Department of Obstetrics and Gynecology (2008‒2019). MATERIALS AND METHODS: The retrospective analysis of perinatal markers and early neonatal morbidity of pregnancies treated with amniopatch. Discussion comparison with the published papers of cases of spontaneous previable rupture of membranes managed expectantly. RESULTS: Out of the total number of pregnancies, 53 met the exclusion criteria, of which 35 were terminated by delivering a live newborn, 3 newborns died during the hospitalization. The following incidence of early complications has been reported in live births: 1) Bronchopulmonary dysplasia (10/35-28.57 %), 2) Newborn respiratory distress syndrome (25/35-71.42 %), 3) Neonatal sepsis (15/35-42.85 %), 4) Intraventricular hemorrhage (14/35-40 %), 5) Periventricular leukomalacia (3/35-8.57 %), 6). Necrotizing enterocolitis (2/35-5.71 %), 7) Retinopathy of prematurity (7/35-20 %) and 8) Foetal compression syndrome (16/35-45.71 %). In a discussion comparison with available publications of expectantly managed pregnancies, we observed a statistically significantly lower incidence of respiratory distress syndrome, retinopathy, and chorioamnionitis in our cohort along with a higher incidence of foetal compression defects. CONCLUSION: Amniopatch can be a therapeutic method for reducing the neonatal mortality associated with RDS, maternal infectious morbidity, and an alternative in patients, who require an active approach to such a compromised pregnancy (Tab. 12, Fig. 1, Ref. 50).

Twin anaemia polycythaemia sequence: a complicated target for prenatal diagnosis, a current state of knowledge.

OBJECTIVES: Processing of available information on TAPS with a focus on the evaluation of the most sensitive and most specific prenatal diagnostic test. MATERIAL AND METHODS: Retrospective analysis of available publications on TAPS with their meta-analytical processing through available electronic medical databases. Evaluation of the most sensitive and specific prenatal diagnostic test with graphical processing of sensitivity and specificity values ​​depending on the TAPS diagnostic criteria used. RESULTS: In total, we found 165 available articles, the oldest from 2007 and the most recent from 2020. Based on the available articles, we evaluated the determination of MCA-PSV with a sensitivity of 83% and a specificity of up to 100% for the currently generally accepted diagnostic criterion TAPS - Delta MCA-PSV > 0.5MoM as the most sensitive and specific method of prenatal diagnosis. CONCLUSIONS: The serial determination of MCA-PSV represents the most sensitive and specific prenatal diagnostic test to date (2020) based on available knowledge. Serial measurement of the MCA-PSV since gestational week 20 every two weeks until delivery represents a potential TAPS screening test for all monochorionic pregnancies. The late, or postnatal diagnosis of TAPS can have serious consequences in the form of intrauterine death of the foetus(es) and increased perinatal mortality and morbidity.

Ultrasound guided vacuum aspiration treatment of caesarean scar ectopic pregnancy

OBJECTIVE: To describe the case of ectopic pregnancy in the scar after caesarean section and its successful treatment using the technique of sonographically controlled vacuum aspiration. CASE REPORT: The case of a 35-year-old patient with a history of two caesarean sections referred by a district gynecologist in the 6th week of pregnancy with suspected pathological localization of pregnancy in a scar after a previous caesarean section. The procedure for the diagnosis and treatment of ectopic pregnancy in the scar after previous caesarean sections has been successfully resolved using sonographically controlled vaginal vacuum aspiration. CONCLUSION: Caesarean scar pregnancy occurs as a complication of previous caesarean section or other uterine instrumental performances. The use of the sonographically controlled vacuum aspiration technique appears to be a successful method of treating pregnancy in a scar after a caesarean section.

Fetal lower urinary tract obstruction: a current overview of intrauterine diagnosis and treatment.

OBJECTIVE: The aim of this review article is to provide a practical and concise overview of diagnosis and management of pregnancy with fetal lower urinary tract obstruction. METHODS: Review of literature and current studies. CONCLUSION: Proper diagnosis and management of isolated fetal lower urinary tract obstruction with oligohydramnios allows appropriate implementation of intrauterine treatment in indicated cases. The treatment is a prevention of pulmonary hypoplasia and also improves renal function; this  finally contributes to the improvement of overall perinatal morbidity and mortality.

Impact of implementing a multifaceted intervention to reduce rates of cesarean section: A quality-improvement study.

OBJECTIVE: To assess the impact of a multifaceted intervention on reducing the rate of cesarean section (CS) without negatively affecting the rate of perinatal mortality. METHODS: A retrospective analysis of CS was performed before and after the implementation of a quality-improvement (QI) intervention in a university-affiliated teaching hospital in the Slovak Republic. All women who gave birth in 2015 (pre-intervention) and 2018 (post-intervention) were included. The different components of the intervention were introduced from September 2016. The main outcome was the overall rate of CS. A subanalysis by Robson groups was undertaken. RESULTS: After the implementation of the QI intervention, there was a 33.5% reduction in the rate of CS compared to the pre-intervention period where the rate reduced from 33.7% to 22.4% (P<0.001; relative risk 0.66, 95% confidence interval [CI] 0.61-0.72; Number Needed to Treat (NNT) 8.8, 95% CI 7.3-11.2). The main contributors were the reduction in elective CS for non-obstetric reasons, a reduction in intrapartum CS for failure to progress, and an increase in the number of vaginal births after CS in the post-intervention period. CONCLUSION: The implementation of the composite QI intervention led to a significant reduction in the rate of CS without affecting the rate of perinatal mortality.

The Oak-wood Extract Robuvit® Improves Recovery and Oxidative Stress after Hysterectomy: A Randomized, Double-blind, Placebo-controlled Pilot Study.

Hysterectomy has a variety of medical indications and improves pre-operative symptoms but might compromise the quality of life during recovery due to symptoms such as fatigue, headache, nausea, depression, or pain. The aim of the present study was to determine the effect of a standardized extract from French oak wood (Quercus robur) containing at least 40% polyphenols of the ellagitannins class, Robuvit®, on convalescence and oxidative stress of women after hysterectomy. Recovery status was monitored with the SF-36 questionnaire. The supplementation with Robuvit® (300 mg/day) during 4 weeks significantly improved general and mental health, while under placebo some items significantly deteriorated. Oxidative stress and enhancement of MMP-9 activity was significantly reduced by Robuvit® versus placebo. After 8 weeks of intervention, the patients' condition improved independently of the intervention. Our results suggest that the use of Robuvit® as a natural supplement relieves post-operative symptoms of patients after hysterectomy and reduces oxidative stress. The study was registered with ID ISRCTN 11457040 (13/09/2019).

Constituents and Metabolites of a French Oak Wood Extract (Robuvit®) in Serum and Blood Cell Samples of Women Undergoing Hysterectomy.

Ellagitannins are signature constituents of oak wood and their consumption has been associated with various health benefits. In vivo, they undergo metabolic degradation including gut microbial metabolism yielding urolithins. Only limited data is available about compounds being present in blood after intake of an extract from French oak wood, Robuvit®. In the course of a randomized, double-blind, controlled clinical investigation, 66 patients undergoing hysterectomy received placebo or 300 mg Robuvit® per day before and over 8 weeks after surgery. Serum and blood cell samples were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). The number of urolithin producers and the urolithin levels increased after intake of Robuvit®. In serum samples, the median concentration of urolithin A was 14.0 ng/ml [interquartile range (IQR) 57.4] after 8 weeks. Urolithin B was determined at 22.3 ng/ml (IQR 12.6), urolithin C at 2.66 ng/ml (IQR 2.08). In blood cells, lower concentrations and only urolithins A and B were detected. A statistically significant association of lower post-surgical pain scores with metabotype A was detected (p < 0.05). To conclude, supplementation with French oak wood extract raised urolithin generation in patients and suggested health advantages for urolithin-producers.

The First Reported Case of Meckel-Gruber Syndrome Associated With Abnormal Karyotype Mosaic Trisomy 17.

Meckel-Gruber syndrome (MKS) is a rare lethal autosomal recessive disorder with typical anomalies including encephalocele, multicystic renal dysplasia, congenital liver fibrosis, and polydactyly. MKS is caused by mutations of genes localized on different chromosomes. Karyotypes of published Meckel-Gruber syndrome cases are without any aberrations. We present a male fetus with meningoencephalocele, multicystic renal dysplasia, congenital liver fibrosis, and other anomalies. Standard cytogenetic examination of cultured fetal skin and muscle fibroblasts showed mosaic trisomy 17. Homozygous deletion in CC2D2A gene was found by Sanger sequencing. This is to our knowledge the first case of genetically confirmed Meckel-Gruber syndrome with incidental cofinding of mosaic trisomy 17. Abnormal karyotype does not exclude diagnosis of MKS with risk of recurrence 25% in next pregnancy. In the case of anomalies typical for Meckel-Gruber syndrome, genetic analysis is indicated.

Prenatal diagnosis and successful intrauterine treatment of severe congenital hypothyroidism associated with fetal goiter.

Congenital hypothyroidism with fetal goiter is a rare condition associated with severe, but possibly preventable, intrauterine and postnatal complications. Ultrasound examination after 20 weeks of pregnancy enables prenatal diagnosis and early treatment. Due to limited transplacental transport of thyroid hormones, direct intrauterine treatment is needed. So far, only a few reports of fetal goitrous hypothyroidism have been published and no consensus on adequate management exists. We present a case of severe fetal goitrous hypothyroidism diagnosed at 23 gestational weeks treated by sequential intra-amniotic administration of L-thyroxin. Treatment resulted in significant goiter reduction and normalization of amniotic hormone levels, and enabled uncomplicated vaginal delivery at term. Current knowledge regarding prenatal diagnosis and intrauterine treatment were unified and applied within this case and a recommendation for clinical practice is provided in this report.

Successful ablation of acardiac twin with Histoacryl.

OBJECTIVE: Acardiac twin occurs in 1:35,000 pregnancies. Several techniques have been described to treat this condition. Some techniques have been suggested as golden standard; however, new are still being tried. CASE REPORT: This is a case of a 32-year-old patient who had successful ablation of the acardiac twin with Histoacryl. The diagnosis of the acardiac twin was made in the 11 weeks + 3 weeks of pregnancy. Due to the development of myocardial hypertrophy and pericardial transudate of the pumping fetus, we had performed ablation of the acardiac twin with Histoacryl in the 21 weeks' +5 weeks' gestation. The procedure was uneventful, and the healthy fetus had no signs of distress. In the 33 weeks' +5 weeks' gestation, she had Cesarean section due to distress of the healthy fetus. The female baby was healthy, weighing 2380 g, Apgar score 9/10. The mummified mass of acardiac fetus weighted 300 g. Nine months later, the child is doing well. CONCLUSION: Histoacryl is suitable for the ablation of an acardiac twin. Further studies are needed to prove the efficacy of this technique.

Prenatal three-dimensional sonographic findings associated with fetal defecation. Case Report.

Routine ultrasonography examination may miss fetal defecation and if seen it can be a source of misinterpretation which can lead to a wrong diagnose and management of pregnancy. We report two rare cases of fetal defecation in the second trimester and we describe 3D sonographic findings associated with this condition.

Beckwith-Wiedemann syndrome with overlapping Perlman syndrome manifestation.

Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome known as exomphalos-macroglossia - gigantism syndrome. Prognosis is good, prenatal diagnosis is important for pregnancy management but might be difficult due to clinical overlap with other syndromes. Perlman syndrome is an overgrowth syndrome with high perinatal mortality, most frequent antenatal findings include polyhydramnios, macrosomia, visceromegaly, nephromegaly and foetal ascites. Authors present a case of prenatally diagnosed BWS with severe ascites as first antenatal finding and lethal course, signs more typical of Perlman syndrome. This combination of clinical signs has not been published yet and may contribute to specification of possible prenatal manifestation of BWS.

Encephalocystocele - uncommon diagnosis in prenatal medicine.

Encephalocystocele is a developmental malformation characterized by brain herniation accompanied with extracranial cystic protrusion of the ventricular system. This nosological unit is often overlooked and insufficiently classified merely as encephalocele. Herein, two exceptionally clear cases of the parieto-occipital cranioschisis with encephalocystocele and congenital hydrocephalus of the lateral ventricles are documented with 2-dimensional/3-dimensional sonographic images and the corresponding MRI findings. In both cases, prenatal diagnosis was confirmed by autopsy.

Amniopatch - possibility of successful treatment of spontaneous previable rupture of membranes in the second trimester of pregnancy by transabdominal intraamiotic application of platelets and cryoprecipitate.

OBJECTIVE: To outline possibility of successful treatment of spontaneous previable rupture of membranes in the second trimester of pregnancy. INTRODUCTION: Spontaneous previable rupture of membranes (SPROM) in the second trimester of pregnancy is one of the most alarming problems in current obstetrics. Perinatal mortality is about 60 %, one third of which represents intrauterine fetal demise. Surviving neonates suffer from various complications. There are different clinical approaches regarding treatment of SPROM. MATERIAL AND METHODS: We present a case of a 30 year old secundigravida with a history of SPROM at 19+1 weeks gestation. Ultrasonographic examination revealed anhydramnios. Genital cultures and laboratory studies ruled out infectious etiology of SPROM. Due to expected poor neonatal outcome, decision to attempt amniopatch as an experimental therapeutic alternative was made at 21+1 weeks gestation (two weeks after SPROM had occurred). Autologous concentrated platelets followed by autologous cryoprecipitate were administered into the amniotic cavity transabdominally under ultrasound guidance. After 3 days sonographic examination showed normal volume of amniotic fluid. On 22 postoperative day, patient notice some leaking of fluid vaginally. Fetal growth was appropriate, amniotic fluid volume was decreased, however, oligohydramnios never progressed to anhydramnios. Pregnancy ended with primary cesarean delivery at 33+1 weeks gestation. Live born male infant with 1750 g birth weight was delivered. Postnatal development was within normal limits. CONCLUSION: Intraamniotic application of "amniopatch" may represent a possibly successful treatment of spontaneous previable rupture of membranes. This case reports the longest stop of the leaking of amniotic fluid and total prolongation of pregnancy with favorable perinatal outcome after "amniopatch" treatment of spontaneous previable rupture of membranes in the second trimester so far published in available literature.

Extreme elevation of placental alkaline phosphatase as a marker of preterm delivery, placental insufficiency and low birth weight.

OBJECTIVE: Clinical case of extremely elevated levels of alkaline phosphatase (ALP) enzyme detected in the 3rd trimester of gestation, the diagnostic and therapeutic procedures, delivery and puerperium are presented. The paper also offers a review of the currently available bibliographical data of the issue. METHODS AND RESULTS: The case presents a 23-year-old secundipara with clinical problems in her 3rd trimester, namely a generalized pruritus. The gestation had signs of asymmetrical fetal hypotrophy induced by placental insufficiency. Laboratory tests showed elevated (as much as a 10.5-fold increase) values of alkaline phosphatase enzyme, 94.05% of which was placental isoenzyme. The patient also had clinical symptoms of a preterm delivery. The spontaneous delivery occurred in 36 week of gestation. The postpuerperium values of alkaline phosphatase returned to normal. CONCLUSION: The authors point out the potential relationship between elevated placental isoenzyme of alkaline phosphatase levels and placental insufficiency and the onset of a preterm delivery.

Reversible asphyxial status in a newborn due to neonatal form of carnitine palmitoyltransferase II deficiency.

OBJECTIVES: To present a term newborn with severe asphyxial status due to dysrrhythmia induced by the neonatal form of carnitine palmitoyltransferase II deficiency (CPT II). RESULTS: Term newborn delivered spontaneously (birth weight 3450 grams, birth length 52 cm, values of Apgar score 10/10) with good direct adaptation, on second day of life he manifested severe asphyxial status followed by cardiorespiratory insufficiency with circulatory failure. After prolonged resuscitation of 3 hours, the child was admitted to our neonatological department. Diagnosis of CPT II was confirmed (free carnitine level in blood 12.2 micromol/l; ratio (C16+C18):1/C2 was 0.760 by tandem mass spectrometry; activity of CPT II in leukocytes was 0.082 micromol/min x gram protein). After appropriate treatment the patient survived the critical period. CONCLUSIONS: Neonatal form of CPT II deficiency is the most severe form and is considered to be invariably fatal. This kind of metabolic disease is congenital, but cardiac problems are not detectable during the prenatal period. Fasting in the early newborn period is a main trigger of CPT II deficiency signs. The authors emphasise the relevance of investigating acylcarnitine profiles and carnitine in serum in all cases of severe postnatal asphyxia and in cases of unusual newborn arrhythmias since some forms of disturbances in beta oxidation of fatty acids are partially treatable.

An alternative management for growth retarded fetus with absent end-diastolic velocity in umbilical artery and normal cardiotocography.

OBJECTIVES: Intrauterine growth retardation (IUGR) is associated with fetal adverse conditions. The most important cause of growth restriction and poor perinatal outcome is chronic fetal hypoxemia (CFH). Adaptation to CFH can be studied by Doppler velocity waveform on umbilical and fetal arteries and cardiotocography (CTG). METHODS: Preterm delivery, as an elimination of CFH, has to be confronted with the risks of prematurity. A special situation may occur when CTG is normal at the absence of end-diastolic velocity (AEDV). AEDV in the umbilical artery precedes the onset of abnormal CTG, whose duration differs considerably among the fetuses. The time after the onset of AEDV in pregnancy may be utilized for performing exact diagnosis by fetal blood analysis. CASE: Primigravida at 30 gestational weeks was referred because of IUGR. IUGR, AEDV, oligohydramnion, and normal fetal anatomy were revealed. CTG was normal. Indication for cordocentesis was to perform cord blood gases analysis and to obtain fetal caryotype. Cordocentesis revealed normal caryotype, values of pH, and fetal blood gases were considered satisfactory. Continuation of pregnancy was decided in spite of persistent AEDV. At 33 gestational weeks pathological CTG was an indication for induction of labor. Labor, delivery, umbilical blood gases, postpartal and neonatal outcome were normal. CONCLUSION: In the case of fetal monitoring controversy assessment of umbilical blood analysis may be crucial. This examination is significant and independent of the interval between cordocentesis and the onset of CTG pathology. This interval may be utilized for intrauterine treatment and for optimizing obstetric management.