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Abstract Background There is an emerging need to systematically investigate the causes for the increased cesarean section rates in Greece and undertake interventions so as to substantially reduce its rates. To this end, the ability of the participating Greek obstetricians to follow evidence-based guidelines and respond to other educational and behavioral interventions while managing labor will be explored, along with barriers and enablers. Herein discussed is the protocol of a stepped-wedge designed intervention trial in Greek maternity units with the aforementioned goals in mind, named ENGAGE (ENhancinG vAGinal dElivery in Greece). Methods Twenty-two selected maternity units in Greece will participate in a multicenter stepped-wedge randomized prospective trial involving 20,000 to 25,000 births, with two of them entering the intervention period of the study each month (stepped randomization). The maternity care units entering the study will apply the suggested interventions for a period of 8–18 months depending on the time they enter the intervention stage of the study. There will also be an initial phase of the study lasting from 8 to 18 months including observation and recording of the routine practice (cesarean section, vaginal birth, and maternal and perinatal morbidity and mortality) in the participating units. The second phase, the intervention period, will include such interventions as the application of the HSOG (the Hellenic Society of Obstetrics and Gynecology) Guidelines on labor management, training on the correct interpretation of cardiotocography, and dealing with emergencies in vaginal deliveries, while the steering committee members will be available to discuss and implement organizational and behavioral changes, answer questions, clarify relevant issues, and provide practical instructions to the participating healthcare professionals during regular visits or video conferences. Furthermore, during the study, the results will be available for the participating units in order for them to monitor their own performance while also receiving feedback regarding their rates. Τhe final 2-month phase of the study will be devoted to completing follow-up questionnaires with data concerning maternal and neonatal morbidities that occurred after the completion of the intervention period. The total duration of the study is estimated at 28 months. The primary outcome assessed will be the cesarean section rate change and the secondary outcomes will be maternal and neonatal morbidity and mortality. Discussion The study is expected to yield new information on the effects, advantages, possibilities, and challenges of consistent clinical engagement and implementation of behavioral, educational, and organizational interventions described in detail in the protocol on cesarean section practice in Greece. The results may lead to new insights into means of improving the quality of maternal and neonatal care, particularly since this represents a shared effort to reduce the high cesarean section rates in Greece and, moreover, points the way to their reduction in other countries. Trial registration NCT 04504500 (ClinicalTrials.gov). The trial was prospectively registered. Ethics Reference No: 320/23.6.2020, Bioethics and Conduct Committee, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

Key Clinical Message Caesarean scar pregnancy represents one of the rarest locations of ectopic pregnancies. It occurs when the blastocyst is implanted in a scar from a previous caesarean section. A dramatic increase of its prevalence has been observed for the last decades, reaching about 21% globally. Early diagnosis and treatment are crucial to avoid maternal morbidity and mortality. Our case presents the characteristic appearance of a caesarean scar pregnancy with full implantation of the gestational sac in the scar, which was managed successfully with laparotomy.

Placental insufficiency and gestational diabetes, which are both serious pregnancy complications, are linked to altered fetal growth, whether restricted or excessive, and result in metabolic dysfunction, hypoxic/oxidative injury, and adverse perinatal outcomes. Although much research has been carried out in this field, the underlying pathogenetic mechanisms have not as yet been fully elucidated. Particularly because of the role it plays in cardiovascular performance, glucose metabolism, inflammation, and oxidative stress, the adipokine apelin was recently shown to be a potential regulator of fetal growth and metabolic programming. This review investigated the numerous biological actions of apelin in utero and aimed to shed more light on its role in fetal growth and metabolic programming. The expression of the apelinergic system in a number of tissues indicates its involvement in many physiological mechanisms, including angiogenesis, cell proliferation, energy metabolism, inflammation, and oxidative stress. Moreover, it appears that apelin has a major function in disorders such as diabetes mellitus, fetal growth abnormalities, fetal hypoxia, and preeclampsia. We herein describe in detail the regulatory effects exerted by the adipokine apelin on fetal growth and metabolic programming while stressing the necessity for additional research into the therapeutic potential of apelin and its mechanisms of action in pregnancy-related disorders.

Introduction: Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides, for use in such products as plastics and cosmetics. This same compound, however, forms naturally in certain foods, both home-cooked and packaged, especially when prepared at high temperatures. We developed and validated a novel reliable technique for the determination of acrylamide in amniotic fluid. Multiple reaction monitoring (MRM) is a targeted mass spectrometry (MS) technique which enables the detection and quantification of particular molecules in a complex mixture. Thanks to its throughput, selectivity, and sensitivity, MRM-MS has been identified as offering an alternative to antibody-based studies for the purpose of biomarker verification. Our aim was to investigate the presence of acrylamide in amniotic fluid and, via the MRM-MS technique, to determine whether there is any correlation between maternal exposure to acrylamide, through a woman’s diet, and fetal growth. Methods: Our amniotic fluid bank included 40 samples from various fetal growth rates, as objectively denoted by the neonatal weight centile at delivery, while our analytical detection method was based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acrylamide was determined with reversed phase chromatography and monitoring of two multiple reaction monitoring (MRM) transitions. Quantification was performed using the matrix-matched calibration curve. Results: Acrylamide was detected at concentrations between 7.1 and 1468 ng/mL in six out of the total of 40 amniotic fluid samples that were used. Our method limit of detection and quantification was 1.4 ng/mL and 4.6 ng/mL, respectively. The repeatability of our method ranged between 11 and 14%, expressed as relative standard deviation levels between 5 and 100 ng/mL. Conclusions: Detection of acrylamide in early second trimester amniotic fluid, for the first time in the literature to our knowledge, raises concerns about fetal health, given that published data on animal studies have attributed a number of birth defects to acrylamide. Our novel LC-MS/MS method for the determination of acrylamide in amniotic fluid proved to be effective and its performance in practice was very accurate, simple, and fast. Validation of the method revealed that the use of a matrix-matched curve is necessary for the quantification.

Abstract Background The interstitial 6p22.3 deletions concern rare chromosomal events affecting numerous aspects of both physical and mental development. The syndrome is characterized by partial deletion of chromosome 6, which may arise in a number of ways. Case presentation We report a 2.8-year old boy presenting with developmental delay and mild dysmorphisms. High-resolution oligonucleotide microarray analysis revealed with high precision a 2.5 Mb interstitial 6p deletion in the 6p22.3 region which encompasses 13 genes. Conclusions Identification and in-depth analysis of cases presenting with mild features of the syndrome will sharpen our understanding of the genetic spectrum of the 6p22.3 deletion.

Background and Objectives: Fetal growth abnormalities increase the risk of negative perinatal and long-term outcomes. Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical to which humans may be exposed in a number of ways, such as from the environment, via various consumer products, and through the individual’s diet. Since the compound possesses estrogen-mimicking properties and exerts epigenetic and genotoxic effects, it has been associated with harmful effects impacting the entire spectrum of human life, including, vitally, the intrauterine period. We investigated the role of maternal exposure to BPA in abnormal fetal growth velocity, both impaired and excessive. Materials and Methods: Amniotic fluid samples were collected from 35 women who underwent amniocentesis early in the second trimester due to medical reasons. Pregnancies were followed until delivery, and birth weights were recorded. The amniotic fluid samples were subsequently divided into three groups based on fetal birth weight, as follows: AGA (appropriate for gestational age), SGA (small for gestational age), and LGA (large for gestational age). Amniotic fluid BPA levels were determined by gas chromatography coupled with mass spectrometry. Results: BPA was detected in 80% (28/35) of our amniotic fluid samples. Median concentration was 281.495 pg/mL and ranged from 108.82 pg/mL to 1605.36 pg/mL. No significant association was observed between the study groups regarding BPA concentration. A significant positive correlation between amniotic fluid BPA concentration and birth weight centile (r = 0.351, p-value = 0.039) was identified. BPA levels were also inversely associated with gestational age in pregnancies at term (between 37 and 41 weeks) (r = −0.365, p-value = 0.031). Conclusions: Our findings suggest that maternal exposure to BPA during the early second trimester of pregnancy can potentially contribute to increased birthweight percentiles and to decreased gestational age in pregnancies at term.

In spite of the great advances made in recent years in prenatal and perinatal medicine, inflammation can still frequently result in injury to vital organs and often constitutes a major cause of morbidity. It is today well established that in neonates—though vulnerability to infection among neonates is triggered by functional impairments in leukocyte adhesion—the decreased expression of cell adhesion molecules also decreases the inflammatory response. It is also clear that the cell adhesion molecules, namely, the integrins, selectins, and the immunoglobulin (Ig) gene super family, all play a crucial role in the inflammatory cascade. Thus, by consolidating our knowledge concerning the actions of these vital cell adhesion molecules during the prenatal period as well as regarding the genetic deficiencies of these molecules, notably leukocyte adhesion deficiency (LAD) I, II, and III, which can provoke severe clinical symptoms throughout the first year of life, it is anticipated that intervention involving blocking the function of cell adhesion molecules in neonatal leukocytes has the potential to constitute an effective therapeutic approach for inflammation. A promising perspective is the potential use of antibody therapy in preterm and term infants with perinatal inflammation and infection focusing on cases in which LAD is involved, while a further important scientific advance related to this issue could be the combination of small peptides aimed at the inhibition of cellular adhesion.