Variation in delivery room management of preterm infants across Europe: a survey of the Union of European Neonatal and Perinatal Societies.

The aim of the present study, endorsed by the Union of European Neonatal and Perinatal Societies (UENPS) and the Italian Society of Neonatology (SIN), was to analyze the current delivery room (DR) stabilization practices in a large sample of European birth centers that care for preterm infants with gestational age (GA) < 33 weeks. Cross-sectional electronic survey was used in this study. A questionnaire focusing on the current DR practices for infants < 33 weeks' GA, divided in 6 neonatal resuscitation domains, was individually sent to the directors of European neonatal facilities, made available as a web-based link. A comparison was made between hospitals grouped into 5 geographical areas (Eastern Europe (EE), Italy (ITA), Mediterranean countries (MC), Turkey (TUR), and Western Europe (WE)) and between high- and low-volume units across Europe. Two hundred and sixty-two centers from 33 European countries responded to the survey. At the time of the survey, approximately 20,000 very low birth weight (VLBW, < 1500 g) infants were admitted to the participating hospitals, with a median (IQR) of 48 (27-89) infants per center per year. Significant differences between the 5 geographical areas concerned: the volume of neonatal care, ranging from 86 (53-206) admitted VLBW infants per center per year in TUR to 35 (IQR 25-53) in MC; the umbilical cord (UC) management, being the delayed cord clamping performed in < 50% of centers in EE, ITA, and MC, and the cord milking the preferred strategy in TUR; the spotty use of some body temperature control strategies, including thermal mattress mainly employed in WE, and heated humidified gases for ventilation seldom available in MC; and some of the ventilation practices, mainly in regard to the initial FiO2 for < 28 weeks' GA infants, pressures selected for ventilation, and the preferred interface to start ventilation. Specifically, 62.5% of TUR centers indicated the short binasal prongs as the preferred interface, as opposed to the face mask which is widely adopted as first choice in > 80% of the rest of the responding units; the DR surfactant administration, which ranges from 44.4% of the birth centers in MC to 87.5% in WE; and, finally, the ethical issues around the minimal GA limit to provide full resuscitation, ranging from 22 to 25 weeks across Europe. A comparison between high- and low-volume units showed significant differences in the domains of UC management and ventilation practices.    Conclusion: Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs. What is Known: • Delivery room (DR) support of preterm infants has a direct influence on both immediate survival and long-term morbidity. • Resuscitation practices for preterm infants often deviate from the internationally defined algorithms. What is New: • Current DR practice and ethical choices show similarities and divergences across Europe. Some areas of assistance, like UC management and DR ventilation strategies, would benefit of standardization. • Clinicians and stakeholders should consider this information when allocating resources and planning European perinatal programs.

Trends in the prenatal diagnosis of trisomy 21 show younger maternal age and shift in the distribution of congenital heart disease over a 20-year period.

Prenatal testing has changed greatly over the past two decades, which may affect the diagnosis of congenital heart disease (CHD) in Down syndrome. The present study aimed to analyze changes in the prevalence and distribution of CHD diagnosed via ultrasonography and fetopathology in 462 fetuses with trisomy 21 between two consecutive 10-year periods (1999-2018), as well as the associations between CHDs, ultrasound markers, and extracardiac malformations. Overall, the frequency of cardiovascular malformations in trisomy 21 was 27.7 and 26.5%, and ultrasound identified 70 and 62% of CHDs during these periods. A profound increase in first-trimester ultrasound findings and associated anomalies with CHDs (ventricular septal defect, Tetralogy of Fallot) since 2009 were observed. Second-trimester nonstructural heart abnormalities were associated with ultrasound anomalies (74%) and major extracardiac malformations (42.9%). During both study periods, mothers carrying fetuses with CHD were significantly younger than those without CHD (p = 0.038, p = 0.009, respectively). Comparing the two 10-year periods, there were no changes in the prevalence and detection of CHDs. Trend analysis revealed that, although the frequency of CHD remained stable, the diagnostic spectrum had shifted between the study periods. Detection of nonstructural heart abnormalities necessitates detailed follow-up for cardiac/extracardiac malformations and chromosomal disorders.

Prenatal Diagnosis of 4q Terminal Deletion and Review of the Literature.

Terminal deletion of chromosome 4 (4q deletion syndrome) is a rare genetic condition that is characterized by a broad clinical spectrum and phenotypic variability. Diagnosis of the distinct condition can be identified by conventional chromosome analysis and small deletions by novel molecular cytogenetic methods such as microarray comparative genome hybridization (aCGH). Prenatal diagnosis is challenging; to date 10 cases have been described. We report a prenatally diagnosed case of de novo 4q deletion syndrome confirmed by conventional karyotyping and FISH due to an elevated combined risk for Down syndrome and prenatal ultrasound findings. aCGH validated the diagnosis and offered exact characterization of the disorder. Cytogenetic and microarray results described a 4q32.1qter terminal deletion of the fetus. Prenatal ultrasound detected multiple nonstructural findings (micrognathia, choroid plexus cysts, echogenic fetal bowel, short femur, and cardiac axis deviation). Pregnancy was terminated at 20 weeks. In addition to the index patient, we reviewed the 10 prenatally published cases of 4q deletion syndrome in the literature and compared these with our results. We summarize the patients' characteristics and prenatal clinical findings. Alterations of maternal serum biochemical factors, an elevated combined risk for trisomies, and distinct ultrasonographic findings can often be observed in cases of prenatal 4q deletion syndrome and may facilitate the otherwise difficult prenatal diagnosis.

Study of patterns of inheritance of premature ovarian failure syndrome carrying maternal and paternal premutations.

BACKGROUND: Premature ovarian failure / primary ovarian insufficiency (POF/POI) associated with the mutations of the FMR1 (Fragile-X Mental Retardation 1) gene belongs to the group of the so-called trinucleotide expansion diseases. Our aim was to analyse the relationship between the paternally inherited premutation (PIP) and the maternally inherited premutation (MIP) by the examination of the family members of women with POF, carrying the premutation allele confirmed by molecular genetic testing. METHODS: Molecular genetic testing was performed in the patients of the 1st Department of Obstetrics and Gynecology with suspected premature ovarian failure. First we performed the southern blot analyses and for the certified premutation cases we used the Repeat Primed PCR. RESULTS: Due to POF/POI, a total of 125 patients underwent genetic testing. The FMR1 gene trinucleotide repeat number was examined in the DNA samples of the patients, and in 15 cases (12%) deviations (CGG repeat number corresponding to premutation or gray zone) were detected. In 6 cases out of the 15 cases the CGG repeat number fell within the range of the so-called gray zone (41-54 CGG repeat) (4.8%, 6/125), and the FMR1 premutation (55-200 CGG repeat) ratio was 7.2% (9/125). In 4 out of the 15 cases we found differences in both alleles, one was a premutation allele, and the other allele showed a repeat number belonging to the gray zone. Out of 15 cases, only maternal inheritance (MIP) was detected in 2 cases, in one case the premutation allele (91 CGG repeat number), while in the other case an allele belonging to the gray zone (41 CGG repeat number) were inherited from their mothers. In 10 out of 15 cases, the patient inherited the premutation allele only from the father (PIP). In 5 out of the 10 cases (50%) the premutation allele was inherited from the father, and the repeat number ranged from 55 to 133. Out of 125 cases, 9 patients had detectable cytogenetic abnormalities (7.2%). CONCLUSIONS: The RP-PCR method can be used to define the smaller premutations and the exact CGG number. Due to the quantitative nature of the RP-PCR, it is possible to detect the mosaicism as well.

Efficacy of Prenatal Ultrasound in Craniospinal Malformations According to Fetopathological and Postnatal Neonatological, Pathological Results.

OBJECTIVE: Our objective is to examine the effectiveness of prenatal ultrasound diagnosis of craniospinal malformations compared to postnatal neonatological and pathological findings. METHODS: Over a 7-year period, we preformed approximately 82.500 prenatal ultrasounds of 26.827 pregnancies. We detected 290 fetuses with 351 craniospinal malformations. RESULTS: Craniospinal abnormalities were found as a part of multiplex malformations in 84/290 cases: in 47/84 cases (55.95%) there was complete concurrence between prenatal and postnatal results. In 15/290 fetuses the craniospinal malformation was associated with chromosomal abnormalities. In 9/15 (60%) of these fetuses, malformations were fully diagnosed with ultrasound. Isolated craniospinal malformations occurred in 191/290 cases, in 162/191 (84.82%) the results of prenatal ultrasonography and postnatal or post abortion examinations showed complete concurrence. In addition to the 290 fetuses with craniospinal malformations, there were an additional 17 who were thought by ultrasound to have a craniospinal malformation, which could not be documented after birth (false positives). CONCLUSIONS: Prenatal ultrasound accurately diagnosed 218/290 (75,17%) craniospinal abnormalities, and partially defined the abnormalities in 9.66%, failed to detect abnormalities in 15.17%, with an approximate 0.06% false detection rate.

[Prenatally diagnosed case of Pallister‒Killian syndrome]. / Praenatalisan diagnosztizált Pallister­Killian-szindróma esete.

Pallister-Killian syndrome (PKS) is a rare, sporadic genetic disorder that is caused by the mosaic presence of a supernumerary marker chromosome, isochromosome 12p. The syndrome is a polydysmorphic condition characterized by mental retardation, craniofacial dysmorphism, hypotonia, seizures, epilepsy and certain organic malformations (diaphragmatic hernia, congenital heart disease). Prenatal diagnosis is challenging due to the mosaic tissue-specific distribution of the chromosomal disorder and highly variable phenotype. Prenatal diagnosis is often accidental, however, appropriate laboratory techniques based on the second trimester ultrasound anomalies provide accurate prenatal diagnosis. We report a case of a 36-year-old primipara with second trimester ultrasound markers (polyhydramnion, ventriculomegaly, rhizomelic micromelia, abnormal facial profile). The patient underwent amniocentesis, the conventional karyotyping revealed a supernumerary chromosome in nearly 50 percent of amniocytes. FISH and targeted multicolour FISH probes verified mosaic tetrasomy of the short arm of chromosome 12 of the fetus. Fetopathological examinations and analysis of fetal tissues and blood confirmed the prenatal diagnosis. To our knowledge, this is the first reported case of prenatally diagnosed Pallister-Killian syndrome in Hungary. Orv Hetil. 2018; 159(21): 847-852.

[Effectiveness of prenatal ultrasound in fetal and neonatal malformations and examination of difficulty and uncertainty factors]. / Magzati-újszülöttkori fejlodési rendellenességek praenatalis ultrahangvizsgálatának eredményessége, a nehézségi és a bizonytalansági faktorok vizsgálata.

INTRODUCTION AND AIM: The birth prevalence of congenital malformations is around 2-3%. The aim of this study was to examine the efficacy of ultrasound diagnostics in detecting congenital malformations. METHOD: We have processed the prenatal sonographic and postnatal clinical details of 1867 inborn abnormalities in 1200 fetuses over a 7-year period. RESULTS: The mean maternal age upon delivery/abortion was 29.96 ± 5.88 years. In 671 cases, the pregnancy concluded in delivery with a mean gestational age of 35.26 ± 4.2 weeks and mean weight of 2408.67 ± 944.41g. In case of the 529 abortions the mean gestational age was 19.88 ± 2.53 weeks. Seventy-three fetuses were chromosomally abnormal, while 211 had multiple malformations. Prenatal ultrasound was highly sensitive in the detection of central nervous system and thoracic anomalies in utero (72.65% vs. 67.7% sensitivity). The detection rate was high in case of abdominal (59.58%), urogenital (54.55%), and limb/skeletal (50%) malformations as well. However, the diagnosis of face/neck anomalies was somewhat less efficient (31.85%). CONCLUSIONS: In approximately half of the cases, postnatally diagnosed abnormalities coincided with the prenatally discovered congenital malformations. The results have confirmed that ultrasonography plays an important role in diagnosing malformations prenatally but it fails to detect all of the developmental abnormalities. Orv Hetil. 2017; 158(45): 1794-1801.

Expression of VEGF in neonatal urinary obstruction: does expression of VEGF predict hydronephrosis?

BACKGROUND: In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. MATERIAL/METHODS: Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1±4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (±2.2SD). Expression of VEGF was detected with immunohistochemistry method. RESULTS: Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. CONCLUSIONS: The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance.

Efficacy of prenatal ultrasonography in diagnosing urogenital developmental anomalies in newborns.

BACKGROUND: Showing a prevalence rate of 0.5-0.8%, urogenital malformations discovered in newborns is regarded relatively common. The aim of this study is to examine the efficacy of ultrasound diagnostics in detecting developmental disorders in the urogenital system. METHODS: We have processed the prenatal sonographic and postnatal clinical details of 175 urogenital abnormalities in 140 newborns delivered with urogenital malformation according to EUROCAT recommendations over a 5-year period between 2006 and 2010. The patients were divided into three groups; Group 1: prenatal sonography and postnatal examinations yielded fully identical results. Group 2: postnatally detected urogenital changes were partially discovered in prenatal investigations. Group 3: prenatal sonography failed to detect the urogenital malformation identified in postnatal examinations. Urogenital changes representing part of certain multiple disorders associated with chromosomal aberration were investigated separately. RESULTS: Prenatal sonographic diagnosis and postnatal results completely coincided in 45%, i.e. 63/140 of cases in newborns delivered with urogenital developmental disorders. In 34/140 cases (24%), discovery was partial, while in 43/140 patients (31%), no urogenital malformation was detected prenatally. No associated malformations were observed in 108 cases, in 57 of which (53%), the results of prenatal ultrasonography and postnatal examinations showed complete coincidence. Prenatally, urogenital changes were found in 11 patients (10%), whereas no urogenital disorders were diagnosed in 40 cases (37%) by investigations prior to birth. Urogenital disorders were found to represent part of multiple malformations in a total of 28 cases as follows: prenatal diagnosis of urogenital malformation and the findings of postnatal examinations completely coincided in three patients (11%), partial coincidence was found in 22 newborns (79%) and in another three patients (11%), the disorder was not detected prenatally. In four newborns, chromosomal aberration was associated with the urogenital disorder; 45,X karyotype was detected in two patients, trisomy 9 and trisomy 18 were found in one case each. CONCLUSION: In approximately half of the cases, postnatally diagnosed abnormalities coincided with the prenatally discovered fetal urogenital developmental disorders. The results have confirmed that ultrasonography plays an important role in diagnosing urogenital malformations but it fails to detect all of the urogenital developmental abnormalities.

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

INTRODUCTION: The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. METHODS: In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. RESULTS: The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3-21.1 microdeletion). In one case, postnatally, the test found Wiedemann-Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. CONCLUSIONS: We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital.

Associations between Fetal Symptoms during Pregnancy and Neonatal Clinical Complications with Toxoplasmosis.

INTRODUCTION: Toxoplasmosis is a parasitism transmitted by Toxoplasma gondii, part of the TORCH complex, the most prevalent parasitism worldwide. It is asymptomatic in immunocompetent individuals but causes severe infections and developmental abnormalities in pregnant women, mainly affecting the central nervous system and the gastrointestinal system. METHODS: In our prospective study, we analyzed cases of recent maternal Toxoplasma infections confirmed by serological testing between 1996 and 2020 at the Department of Obstetrics and Gynecology, Semmelweis University. Amniocentesis, followed by PCR, was performed in cases of recent infection confirmed by serological testing during pregnancy. After birth, a neonatological, microbiological, pediatric neurological and ophthalmological examination and a follow-up was carried out. RESULTS: During the study period, a total of 238 cases of amniotic fluid Toxoplasma PCR testing due to Toxoplasma recent infection were performed. In terms of pregnancies, there were 219 deliveries and seven abortions. Twelve cases had no data available on the outcome of the pregnancy. In total, 133 cases of ultrasound abnormalities were detected during pregnancy, while in 105 cases, no abnormalities were detected on ultrasound examination. During amniocentesis, eight cases of Toxoplasma infection were revealed in amniotic fluid samples by PCR, and in 230 cases, the result was negative. Neonatal follow-up was performed in 139 cases, with no abnormalities during follow-up in 117 cases, and in 22 cases, there was a detectable complication that was likely to be related to Toxoplasma infection. In all 22 cases, amniotic fluid PCR Toxoplasma testing was negative. CONCLUSIONS: The most common ultrasound abnormalities involve the nervous system and the gastrointestinal system. In cases of suspicion, it is recommended to perform amniocentesis Toxoplasma PCR testing besides the indirect methods to help the pregnant woman decide whether to carry the pregnancy to term. During follow-up, a multidisciplinary team experienced in pregnancies complicated by toxoplasmosis must carry out the follow-up, care and subsequent development.

Screening of premature ovarian insufficiency associated genes in Hungarian patients with next generation sequencing.

BACKGROUND: Premature ovarian insuffiency (POI) is one of the main cause behind infertility. The genetic analysis of POI should be part of the clinical diagnostics, as several genes have been implicated in the genetic background of it. The aim of our study was to analyse the genetic background of POI in a Hungarian cohort. METHODS: The age of onset was between 15 and 39 years. All patients had the 46,XX karyotype and they were prescreened for the most frequent POI associated FMR1 premutation. To identify genetic alterations next-generation sequencing (NGS) of 31 genes which were previously associated to POI were carried out in 48 unrelated patients from Hungary. RESULTS: Monogenic defect was identified in 16.7% (8 of 48) and a potential genetic risk factor was found in 29.2% (14 of 48) and susceptible oligogenic effect was described in 12.5% (6 of 48) of women with POI using the customized targeted panel sequencing. The genetic analysis identified 8 heterozygous damaging and 4 potentially damaging variants in POI-associated genes. Further 10 potential genetic risk factors were detected in seven genes, from which EIF2B and GALT were the most frequent. These variants were related to 15 genes: AIRE, ATM, DACH2, DAZL, EIF2B2, EIF2B4, FMR1, GALT, GDF9, HS6ST2, LHCGR, NOBOX, POLG, USP9X and XPNPEP2. In six cases, two or three coexisting damaging mutations and risk variants were identified. CONCLUSIONS: POI is characterized by heterogenous phenotypic features with complex genetic background that contains increasing number of genes. Deleterious variants, which were detected in our cohort, related to gonadal development (oogenesis and folliculogenesis), meiosis and DNA repair, hormonal signaling, immune function, and metabolism which were previously associated with the POI phenotype. This is the first genetic epidemiology study targeting POI associated genes in Hungary. The frequency of variants in different POI associated genes were similar to the literature, except EIF2B and GALT. Both of these genes potential risk factor were detected which could influence the phenotype, although it is unlikely that they can be responsible for the development of the disease by themselves. Advances of sequencing technologies make it possible to aid diagnostics of POI Since individual patients show high phenotypic variance because of the complex network controlling human folliculogenesis. Comprehensive NGS screening by widening the scope to genes which were previously linked to infertility may facilitate more accurate, quicker and cheaper genetic diagnoses for POI. The investigation of patient's genotype could support clinical decision-making process and pave the way for future clinical trials and therapies.

Heterogenic Genetic Background of Distal Arthrogryposis-Review of the Literature and Case Report.

Distal arthrogryposis (DA) is a skeletal muscle disorder that is characterized by the presence of joint contractures in various parts of the body, particularly in the distal extremities. In this study, after a systematic review of the literature, we present a case report of a non-consanguineous family. In our case, the first-trimester ultrasound was negative, and the presence of the affected mother was not enough for the parents to consent to us performing invasive amniotic fluid sampling. The second-trimester ultrasound showed clear abnormalities suggestive of arthrogryposis. Whole-exome sequencing was performed and an autosomal dominantly inherited disease-associated gene was identified. In our case, a pathogenic variant in the TNNT3 gene c.188G>A, p.Arg63His variant was identified. The mother, who had bilateral clubfoot and hand involvement in childhood, carried the same variant. The TNNT3 gene is associated with distal arthrogryposis type 2B2, which is characterized by congenital contractures of the distal limb joints and facial dysmorphism. In the ultrasound, prominent clubfoot was identified, and the mother, who also carried the same mutation, had undergone surgeries to correct the clubfoot, but facial dysmorphism was not detected. Our study highlights the importance of proper genetic counseling, especially in an affected parent(s), and close follow-up during pregnancy.

Laryngeal Mask Airway in Neonatal Resuscitation: A Survey of the Union of European Neonatal and Perinatal Societies.

INTRODUCTION: Laryngeal mask airway (LMA) use in neonatal resuscitation is limited despite existing evidence and recommendations. This survey investigated the knowledge and experience of healthcare providers on the use of the LMA and explored barriers and solutions for implementation. METHODS: This online, cross-sectional survey on LMA in neonatal resuscitation involved healthcare professionals of the Union of European Neonatal and Perinatal Societies (UENPS). RESULTS: A total of 858 healthcare professionals from 42 countries participated in the survey. Only 6% took part in an LMA-specific course. Some delivery rooms were not equipped with LMA (26.1%). LMA was mainly considered after the failure of a face mask (FM) or endotracheal tube (ET), while the first choice was limited to neonates with upper airway malformations. LMA and FM were considered easier to position but less effective than ET, while LMA was considered less invasive than ET but more invasive than FM. Participants felt less competent and experienced with LMA than FM and ET. The lack of confidence in LMA was perceived as the main barrier to its implementation in neonatal resuscitation. More training, supervision, and device availability in delivery wards were suggested as possible actions to overcome those barriers. CONCLUSION: Our survey confirms previous findings on limited knowledge, experience, and confidence with LMA, which is usually considered an option after the failure of FM/ET. Our findings highlight the need for increasing the availability of LMA in delivery wards. Moreover, increasing LMA training and having an LMA expert supervisor during clinical practice may improve the implementation of LMA use in neonatal clinical practice.

A Survey of the Union of European Neonatal and Perinatal Societies on Neonatal Respiratory Care in Neonatal Intensive Care Units.

(1) Background: Our survey aimed to gather information on respiratory care in Neonatal Intensive Care Units (NICUs) in the European and Mediterranean region. (2) Methods: Cross-sectional electronic survey. An 89-item questionnaire focusing on the current modes, devices, and strategies employed in neonatal units in the domain of respiratory care was sent to directors/heads of 528 NICUs. The adherence to the "European consensus guidelines on the management of respiratory distress syndrome" was assessed for comparison. (3) Results: The response rate was 75% (397/528 units). In most Delivery Rooms (DRs), full resuscitation is given from 22 to 23 weeks gestational age. A T-piece device with facial masks or short binasal prongs are commonly used for respiratory stabilization. Initial FiO2 is set as per guidelines. Most units use heated humidified gases to prevent heat loss. SpO2 and ECG monitoring are largely performed. Surfactant in the DR is preferentially given through Intubation-Surfactant-Extubation (INSURE) or Less-Invasive-Surfactant-Administration (LISA) techniques. DR caffeine is widespread. In the NICUs, most of the non-invasive modes used are nasal CPAP and nasal intermittent positive-pressure ventilation. Volume-targeted, synchronized intermittent positive-pressure ventilation is the preferred invasive mode to treat acute respiratory distress. Pulmonary recruitment maneuvers are common approaches. During NICU stay, surfactant administration is primarily guided by FiO2 and SpO2/FiO2 ratio, and it is mostly performed through LISA or INSURE. Steroids are used to facilitate extubation and prevent bronchopulmonary dysplasia. (4) Conclusions: Overall, clinical practices are in line with the 2022 European Guidelines, but there are some divergences. These data will allow stakeholders to make comparisons and to identify opportunities for improvement.

Biostatistical evaluation of the effectiveness of fetal ultrasound diagnostics with application of new uncertainty factor and difficulty factor in cases of craniofacial malformations-gray zone in biostatistics for imaging procedures.

Background: The craniofacial malformations occur less frequently, with a prevalence rate of approximately 0.1%. Our aim is to investigate the effectiveness of prenatal ultrasound in the detection of the craniofacial abnormalities. Methods: In our study, we have processed the prenatal sonographic and postnatal clinical and fetopathological data of 242 anatomical deviations of 218 fetuses with craniofacial malformations over a 12-year period. The patients were divided into three groups: Group I, Totally Recognized; Group II, Partially Recognized; Group III, Not Recognized. To characterize the diagnostics of disorders we developed the Uncertainty Factor F (U) = P (Partially Recognized)/[P (Partially Recognized) + T (Totally Recognized)] and Difficulty factor F (D) = N (Not Recognized)/[P (Partially Recognized) + T (Totally Recognized)]. Results: Prenatal ultrasound diagnosis of fetuses with facial and neck malformations completely coincided in 71/218 cases (32.6%) with postnatal/fetopathological findings. In 31/218 cases (14.2%) the detection was only partial, while in 116/218 cases no craniofacial malformations were diagnosed prenatally (53.2%). The Difficulty Factor was high or very high in almost each disorder group, with a cumulative score of 1.28. The Uncertainty Factor cumulative score was 0.32. Conclusions: The effectiveness of the detection of the facial and neck malformations was low (29.75%). The Uncertainty Factor F (U) and Difficulty Factor F (D) parameters, which characterized the difficulties of the prenatal ultrasound examination well.

European guidelines on perinatal care: corticosteroids for women at risk of preterm birth.

of recommendationsCorticosteroids should be administered to women at a gestational age between 24+0 and 33+6 weeks, when preterm birth is anticipated in the next seven days, as these have been consistently shown to reduce neonatal mortality and morbidity. (Strong-quality evidence; strong recommendation). In selected cases, extension of this period up to 34+6 weeks may be considered (Expert opinion). Optimal benefits are found in infants delivered within 7 days of corticosteroid administration. Even a single-dose administration should be given to women with imminent preterm birth, as this is likely to improve neurodevelopmental outcome (Moderate-quality evidence; conditional recommendation).Either betamethasone (12 mg administered intramuscularly twice, 24-hours apart) or dexamethasone (6 mg administered intramuscularly in four doses, 12-hours apart, or 12 mg administered intramuscularly twice, 24-hours apart), may be used (Moderate-quality evidence; Strong recommendation). Administration of two "all" doses is named a "course of corticosteroids".Administration between 22+0 and 23+6 weeks should be considered when preterm birth is anticipated in the next seven days and active newborn life-support is indicated, taking into account parental wishes. Clear survival benefit has been observed in these cases, but the impact on short-term neurological and respiratory function, as well as long-term neurodevelopmental outcome is still unclear (Low/moderate-quality evidence; Weak recommendation).Administration between 34 + 0 and 34 + 6 weeks should only be offered to a few selected cases (Expert opinion). Administration between 35+0 and 36+6 weeks should be restricted to prospective randomized trials. Current evidence suggests that although corticosteroids reduce the incidence of transient tachypnea of the newborn, they do not affect the incidence of respiratory distress syndrome, and they increase neonatal hypoglycemia. Long-term safety data are lacking (Moderate quality evidence; Conditional recommendation).Administration in pregnancies beyond 37+0 weeks is not indicated, even for scheduled cesarean delivery, as current evidence does not suggest benefit and the long-term effects remain unknown (Low-quality evidence; Conditional recommendation).Administration should be given in twin pregnancies, with the same indication and doses as for singletons. However, existing evidence suggests that it should be reserved for pregnancies at high-risk of delivering within a 7-day interval (Low-quality evidence; Conditional recommendation). Maternal diabetes mellitus is not a contraindication to the use of antenatal corticosteroids (Moderate quality evidence; Strong recommendation).A single repeat course of corticosteroids can be considered in pregnancies at less than 34+0 weeks gestation, if the previous course was completed more than seven days earlier, and there is a renewed risk of imminent delivery (Low-quality evidence; Conditional recommendation).

Effect of New Peripudendal Block (PPB) in the Second Stage of Labour on Perineal Relaxation and on the Reduction of Episiotomy Rate: A Randomized Control Trial.

Methods: In a prospective randomized study, we examined the extent to which the PPB we developed changed the rate of episiotomies, injury rates. Results: A total of 333 primiparas and 324 multiparas were included in the study. In the case of primiparas, we used the PPD procedure in 133 cases, while in the case of multiparas, we used it in 103 cases. The rate of episiotomy in primiparas was 89/133 (66.9%) with PPD and 181/200 (90.5%) without PPD (p < 0.02). In multiparas, the episiotomy rate was 30/103 (29.1%) with PPD and 140/221 (63.3%) without PPD (p < 0.02). In the case of primiparas, the rate of perineal injury and lesion was 33/133 (24.8%) with PPD, while without PPD it was 12/200 (6.0%). Examining the need for all surgical care (due to episiotomy and/or injury), a total of 103/133 cases of operative surgery were required with PPD (77/4%) while 183/200 cases were required without PPD (91.5%)(p < 0.02). In the case of multiparas, the rate of perineal injury and lesion was 11/103 (10.7%) with PPD, while without PPD it was 9/221 (4.1%). In the case of multiparas, a total of 41/103 cases required surgical care with PPD (39.8%), while without PPD, 147/221 cases required surgical care (66.5%)(p < 0.02). Conclusion: The PPB is simpler, requires less medication, can be easily mastered, and perineal relaxation can also be observed, reducing the need for an episiotomy.

Case report: A particularly rare case of endogenous hyperinsulinemic hypoglycemia complicated with pregnancy treated with short-acting somatostatin analog injections.

Hyperinsulinemic hypoglycemia is a rare disease, and only two cases complicated with pregnancy were published previously when our patient became pregnant. We introduce a successful management of a pregnancy in a patient with endogenous hyperinsulinemic hypoglycemia, a condition also known as non-insulinoma pancreatogenous hypoglycemia syndrome or formerly as nesidioblastosis. A 29-year-old female patient was treated with endogenous hyperinsulinemic hypoglycemia since the age of 4 months, taking daily 3 × 75 mg diazoxide, which adds up to 225 mg per day. Adequate glycemic control could be achieved with this therapy. Genetic testing and various imaging examinations were carried out earlier to specify the disease and to exclude focal forms. The patient came to the clinic with a positive pregnancy test and consequential hypoglycemic episodes. Hospital admission was needed to correct the metabolic condition. Although the patient was informed about the potential risks, she decided to carry out the pregnancy. According to the quite limited literature, somatostatin analogs are the only therapy used previously during pregnancy in hyperinsulinemic hypoglycemic patients. One publication reported normal pregnancy outcomes, but in another case, restricted fetal growth was observed. In our case, we stopped diazoxide and parallelly introduced short-acting somatostatin analog octreotide in the therapy, and further dietetic changes were proposed. In addition to daily regular self-blood glucose monitoring, regular gynecological controls were carried out monthly, and healthy fetal development was confirmed. The patient gave birth to her first child, a well-developed female neonate, in the 38th week, by a cesarean section.

European guidelines on perinatal care- Peripartum care Episiotomy.

OF RECOMMENDATIONS1. Episiotomy should be performed by indication only, and not routinely (Moderate quality evidence +++-; Strong recommendation). Accepted indications for episiotomy are to shorten the second stage of labor when there is suspected fetal hypoxia (Low quality evidence ++-; Weak recommendation); to prevent obstetric anal sphincter injury in vaginal operative deliveries, or when obstetric sphincter injury occurred in previous deliveries (Moderate quality evidence +++-; Strong recommendation)2. Mediolateral or lateral episiotomy technique should be used (Moderate quality evidence +++-; Strong recommendation). Labor ward staff should be offered regular training in correct episiotomy techniques (Moderate quality evidence +++-; Strong recommendation).3. Pain relief needs to be considered before episiotomy is performed, and epidural analgesia may be insufficient. The perineal skin needs to be tested for pain before an episiotomy is performed, even when an epidural is in place. Local anesthetics or pudendal block need to be considered as isolated or additional pain relief methods (Low quality evidence ++-; Strong recommendation).4. After childbirth the perineum should be carefully inspected, and the anal sphincter palpated to identify possible injury (Moderate quality evidence +++-; Strong recommendation). Primary suturing immediately after childbirth should be offered and a continuous suturing technique should be used when repairing an uncomplicated episiotomy (High quality evidence ++++; Strong recommendation).