Infant, Neonatal, and Post-neonatal Mortality in Greece: A Nationwide Time-Trend Analysis.

INTRODUCTION: Infant mortality is a crucial perinatal measure and is also regarded as an important public health indicator. This study aimed to comprehensively present time trends in infant, neonatal, and post-neonatal mortality in Greece. METHODS: The annual infant mortality rate (IMR), the neonatal mortality rate (NMR), and the post-neonatal mortality rate (PNMR) were calculated based on official national data obtained from the Hellenic Statistical Authority, spanning 67 years from 1956 to 2022. The time trends of the mortality rates were evaluated using joinpoint regression analysis, and the annual percent changes (APC) and the overall average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI). RESULTS: The IMR exhibited accelerating declines over more than 50 years, with an APC of -1.9 (-2.8 to -1.0) from 1956 to 1968, -5.4 (-5.6 to -5.2) from 1968 to 1999, and -7.3 (-8.9 to -5.7) between 1999 and 2008. In 2008, IMR reached its all-time low of 2.7 per 1,000 live births, down 16.6-fold from its peak at 44.1 per 1,000 live births in 1957. This improving trend was reversed following the onset of the economic crisis in the country, leading to a 57% increase in IMR from 2008 to 2016, with an upward trend APC of 3.4 (1.2 to 5.5). In the recent period 2016-2022, there was an improvement with an APC of -3.7 (-6.2 to -1.1), resulting in an IMR of 3.1 per 1,000 live births in 2022. The decrease in IMR was estimated to have prevented 209,109 infant deaths in the country from 1958 to 2022. From 1956 to 2022, the IMR decreased with an AAPC of -3.9 (-4.3 to -3.4), while the PNMR saw a decline with an AAPC of -4.5 (-5.1 to -3.9) and the NMR with an AAPC of -3.2 (-3.7 to -2.6). CONCLUSION: Greece achieved an impressive decrease in infant mortality rates, but this progress was halted and completely reversed during the economic crisis. Although there have been some recent improvements after the country's economic recovery, the rates have yet to reach pre-crisis levels.

Ectopic pregnancy with full implantation of the gestational sac in the caesarean section scar managed successfully with laparotomy.

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.

Association between cytokine polymorphisms and recurrent pregnancy loss: A review of current evidence.

Cytokines are a type of protein that play an important role in the immune response and can also affect many physiological processes in the body. Cytokine polymorphisms refer to genetic variations or mutations that occur within the genes that code for cytokines, which may affect the level of cytokine production and function. Some cytokine polymorphisms have been associated with an increased risk of developing certain diseases, while others may be protective or have no significant effect on health. In recent years, the role of cytokine polymorphisms in the development of recurrent pregnancy loss (RPL) has been studied. RPL or miscarriage is defined as the occurrence of two or more consecutive pregnancy losses before the 20th week of gestation. There are diverse causes leading to RPL, including genetic, anatomical, hormonal, and immunological factors. With regard to cytokine polymorphisms, a few of them have been found to be associated with an increased risk of RPL, for instance, variations in the genes that code for interleukin-6, tumor necrosis factor-alpha, and interleukin-10. The exact mechanisms by which cytokine polymorphisms affect the risk of recurrent miscarriage are still being studied, and further research is essential to fully understand this complex condition. This brief review aims to summarize the recent literature on the association between cytokine polymorphisms and RPL.

Factors Influencing the Decision-Making Process for Undergoing Invasive Prenatal Testing.

Invasive prenatal testing, amniocentesis, and chorionic villus sampling offer insights into fetal genetic integrity and health, but carry inevitable minor risks of miscarriage and infection, thus complicating the decision-making process for parents. Previous research has revealed several factors that influence the decision to undergo invasive prenatal testing, including demographic, clinical, and psychological aspects, and attitudes towards testing. Informed choice, involving understanding options and aligning them with personal values, is crucial, with healthcare providers playing a key role in offering unbiased information. This systematic review aims to gather and synthesize literature data on the above factors to draw conclusions to aid antenatal care providers in supporting couples to make more informed decisions about their prenatal care. A systematic search was performed in PubMed and PsycInfo databases using the appropriate keywords and an in-depth evaluation of the studies retrieved followed. Finally, 17 articles were eligible for our review investigating the decision-making process of invasive prenatal testing. Factors like maternal age, education, and ethnicity are pivotal during the decision-making process. Clinical characteristics also influence decisions and women with pregnancies categorized as high-risk or those who have undergone fertility treatment display a preference for invasive testing. There seems to be a direct correlation between a woman's willingness to consider pregnancy termination, deeply rooted in psychological and moral stances, and the inclination to undergo invasive testing. In the patient decision-making process, the provision and depth of knowledge are of paramount importance. A comprehensive understanding facilitates more informed decisions. Finally, attitudes towards termination of pregnancy, as another factor influencing the decision-making process, reveal a nuanced landscape where personal beliefs, religious considerations, legal restrictions, and perspectives on disability converge. Within this complex context, religion emerges as an important determinant, shaping individuals' views on the morality of abortion. This review sheds light on the most important factors influencing the couples' consent for invasive prenatal testing. Healthcare professionals must identify which factors are critical in every specific case among several sociodemographic, clinical, emotional, and religious factors. Thus, they will be able to provide balanced and comprehensive information to help couples under this stressful procedure. We advocate for a patient-centered multidisciplinary approach while navigating couples through the intricate landscape of decision-making concerning invasive prenatal testing.

The Contribution of Multiple Pregnancies in Stillbirths in Greece: A Time-Trend Analysis.

Introduction Multiple pregnancy is an established risk factor for fetal death. This study aimed to examine the impact of multifetal pregnancies on stillbirth rates (SBRs) in the Greek population. Methods Data on live births and stillbirths by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. The SBR for multiple and single gestations, and the population attributable risk (%) (PAR (%)) stillbirth attributable to multifetal gestations were calculated, and temporal trends were assessed using joinpoint regression analysis, with annual percentage changes (APC) and 95% confidence interval (95% CI). Results In the period 1957-2021, multiple pregnancies accounted for 9.4% of total stillbirths in Greece and the overall relative risk of fetal death among multifetal gestations was 3.34, in comparison with singletons. The SBR in multiple births remained unchanged from 1957 to 1976 and showed downward trends from 1976 to 2021 (APC = -3.0, 95% CI: -3.4 to -2.7, p < 0.001). PAR (%), after two decades of stability, showed an increasing trend over the period 1975-2011 (APC = 3.4, 95% CI: 2.8 to 4.0, p < 0.001), which was reversed in the more recent decade 2011-2021 (APC = -6.1, 95% CI: -9.6 to -2.5, p = 0.001), with PAR (%) decreasing from a historical high of 19.3% in 2012 to 8.6% in 2021. Conclusion The high incidence of multiple births has a considerable impact on stillbirth rates in the Greek population. The recent downward trends of SBR and PAR (%) of multiple gestations are encouraging, however more measures and targeted interventions are needed to improve perinatal outcomes in multifetal gestation.

Second Trimester Amniotic Fluid Angiotensinogen Levels Linked to Increased Fetal Birth Weight and Shorter Gestational Age in Term Pregnancies.

BACKGROUND: Despite the considerable progress made in recent years in fetal assessment, the etiology of fetal growth disturbances is not as yet well understood. In an effort to enhance our knowledge in this area, we investigated the associations of the amniotic fluid angiotensinogen of the renin-angiotensin system with fetal growth abnormalities. METHODS: We collected amniotic fluid samples from 70 pregnant women who underwent amniocentesis during their early second trimester. Birth weight was documented upon delivery, after which the embryos corresponding to the respective amniotic fluid samples were categorized into three groups as follows: small for gestational age (SGA), appropriate for gestational age (AGA), and large for gestational age (LGA). Amniotic fluid angiotensinogen levels were determined by using ELISA kits. RESULTS: Mean angiotensinogen values were 3885 ng/mL (range: 1625-5375 ng/mL), 4885 ng/mL (range: 1580-8460 ng/mL), and 4670 ng/mL (range: 1995-7250 ng/mL) in the SGA, LGA, and AGA fetuses, respectively. The concentrations in the three groups were not statistically significantly different. Although there were wide discrepancies between the mean values of the subgroups, the large confidence intervals in the three groups negatively affected the statistical analysis. However, multiple regression analysis revealed a statistically significant negative correlation between the angiotensinogen levels and gestational age and a statistically significant positive correlation between the birth weight and angiotensinogen levels. DISCUSSION: Our findings suggest that fetal growth abnormalities did not correlate with differences in the amniotic fluid levels of angiotensinogen in early second trimester pregnancies. However, increased angiotensinogen levels were found to be consistent with a smaller gestational age at birth and increased BMI of neonates.

Investigating the Association of Assisted Reproduction Techniques and Adverse Perinatal Outcomes.

BACKGROUND: Infertility affects about 80 million individuals worldwide and 10-15% of couples at reproductive age will seek medical assistance. There is increasing evidence that pregnancies after Assisted Reproduction Techniques (ART) are associated with pre-term birth, low birthweight, congenital defects, and increased mortality rates. The aim of this review is to assess all the published literature and provide an updated review on the effect of assisted conception and perinatal and neonatal outcomes. METHODS: Comprehensive research on Pubmed/Medline, Scopus, and Google scholar electronic databases was conducted from July 2023 up to September 2023, using the terms assisted reproductive techniques, ART, in vitro fertilization, IVF, intracytoplasmic sperm injection, ICSI, preterm birth, PTB, low birth weight, LBW, chromosomal defects, congenital defects, and hypospadias. In total, 87 full text articles were retrieved and after a careful evaluation, 31 studies were selected for data extraction. RESULTS: Our review demonstrated a higher risk of congenital and chromosomal defects, and a higher incidence of male genital tract defects and heart defects in ART pregnancies. Regarding pre-term birth, our results were contradictory. CONCLUSIONS: Although assisted reproduction techniques are associated with increased risks, they are safe regarding perinatal outcomes and couples should not be discouraged from utilizing them. Our results aim to alert clinicians to these specific outcomes and offer more personalized care and counseling to infertile couples and their children.

Detection and Quantification of Acrylamide in Second Trimester Amniotic Fluid Using a Novel LC-MS/MS Technique to Determine Whether High Acrylamide Content during Pregnancy Is Associated with Fetal Growth.

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.

Detection and Quantification of Neurotrophin-3 (NT-3) and Nerve Growth Factor (NGF) Levels in Early Second Trimester Amniotic Fluid: Investigation into a Possible Correlation with Abnormal Fetal Growth Velocity Patterns.

BACKGROUND: Abnormal fetal growth is associated with adverse perinatal and long-term outcomes. The pathophysiological mechanisms underlying these conditions are still to be clarified. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are two neurotrophins that are mainly involved in the neuroprotection process, namely promotion of growth and differentiation, maintenance, and survival of neurons. During pregnancy, they have been correlated with placental development and fetal growth. In this study, we aimed to determine the early 2nd trimester amniotic fluid levels of NGF and NT-3 and to investigate their association with fetal growth. METHODS: This is a prospective observational study. A total of 51 amniotic fluid samples were collected from women undergoing amniocentesis early in the second trimester and were stored at -80 °C. Pregnancies were followed up until delivery and birth weight was recorded. Based on birth weight, the amniotic fluid samples were divided into three groups: appropriate for gestational age (AGA), small for gestational age (SGA), and large for gestational age (LGA). NGF and NT-3 levels were determined by using Elisa kits. RESULTS: NGF concentrations were similar between the studied groups; median values were 10.15 pg/mL, 10.15 pg/mL, and 9.14 pg/mL in SGA, LGA, and AGA fetuses, respectively. Regarding NT-3, a trend was observed towards increased NT-3 levels as fetal growth velocity decreased; median concentrations were 11.87 pg/mL, 15.9 pg/mL, and 23.5 pg/mL in SGA, AGA, and LGA fetuses, respectively, although the differences among the three groups were not statistically significant. CONCLUSIONS: Our findings suggest that fetal growth disturbances do not induce increased or decreased production of NGF and NT-3 in early second trimester amniotic fluid. The trend observed towards increased NT-3 levels as fetal growth velocity decreased shows that there may be a compensatory mechanism in place that operates in conjunction with the brain-sparing effect. Further associations between these two neurotrophins and fetal growth disturbances are discussed.

Prenatal Exposure to Bisphenol A: Is There an Association between Bisphenol A in Second Trimester Amniotic Fluid and Fetal Growth?

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.

Is There a Correlation between Apelin and Insulin Concentrations in Early Second Trimester Amniotic Fluid with Fetal Growth Disorders?

INTRODUCTION: Fetal growth disturbances place fetuses at increased risk for perinatal morbidity and mortality. As yet, little is known about the basic pathogenetic mechanisms underlying deranged fetal growth. Apelin is an adipokine with several biological activities. Over the past decade, it has been investigated for its possible role in fetal growth restriction. Most studies have examined apelin concentrations in maternal serum and amniotic fluid in the third trimester or during neonatal life. In this study, apelin concentrations were examined for the first time in early second-trimester fetuses. Another major regulator of tissue growth and metabolism is insulin. MATERIALS AND METHODS: This was a prospective observational cohort study. We measured apelin and insulin concentrations in the amniotic fluid of 80 pregnant women who underwent amniocentesis in the early second trimester. Amniotic fluid samples were stored in appropriate conditions until delivery. The study groups were then defined, i.e., gestations with different fetal growth patterns (SGA, AGA, and LGA). Measurements were made using ELISA kits. RESULTS: Apelin and insulin levels were measured in all 80 samples. The analysis revealed statistically significant differences in apelin concentrations among groups (p = 0.007). Apelin concentrations in large for gestational age (LGA) fetuses were significantly lower compared to those in AGA and SGA fetuses. Insulin concentrations did not differ significantly among groups. CONCLUSIONS: A clear trend towards decreasing apelin concentrations as birthweight progressively increased was identified. Amniotic fluid apelin concentrations in the early second trimester may be useful as a predictive factor for determining the risk of a fetus being born LGA. Future studies are expected/needed to corroborate the present findings and should ideally focus on the potential interplay of apelin with other known intrauterine metabolic factors.

Temporal Trends in Stillbirth in Greece: A Longitudinal Population-Based Study.

INTRODUCTION: Stillbirths are a major public health issue and a key population health indicator. The aim of this study was to comprehensively investigate and present time trends in stillbirth in Greece. METHODS: Data on all live births and stillbirths were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021 and the annual stillbirth rate (SBR) was calculated, defined as the number of stillbirths per 1,000 live births and stillbirths (total births). Trends in the SBR were assessed using joinpoint regression analysis with calculation of the annual percent change (APC) with a 95% confidence interval (95% CI) and level of statistical significance p<0.05. RESULTS: The SBR in Greece, after an initial increasing trend (1957-1965: APC=2.6, 95% CI: 0.5 to 4.7, p=0.016), and an all-time high of 15.8 per 1,000 births in 1966, recorded a four decades period of continuous improvement (1965-2003: APC=3.0, 95% CI: -3.2 to -2.8, p<0.001) and reached a historic low in 2008 (3.3 per 1,000 births) (a decrease by 79%). However, the SBR stagnated at an elevated level during the decade 2006-2016 and showed a steeply upward trend during the most recent period 2016-2021 (APC=7.4, 95% CI: 3.0 to 12.1, p=0.001). In 2021, the SBR was 5.3 per 1,000 births, 60% up from 2008. It was estimated that the SBR improvement for the 1967-2021 period resulted in 50,914 stillbirths averted (7.9 per 1,000 births), but the recent increase in the SBR has led to 1,200 additional fetal deaths (1.0 per 1,000 births) during 2009-2021. CONCLUSION: After an impressive decline for almost four decades the SBR gradually deteriorated during the economic crisis and finally showed an alarming rising trend after 2015, resulting in an increasing burden of fetal deaths in Greece. Further public health interventions are needed to address preventable risk factors and ensure access to optimized antenatal monitoring.

Apremilast for biologic-naïve, peripheral psoriatic arthritis, including patients with early disease: results from the APROACH observational prospective study.

To evaluate the effect of the phosphodiesterase 4 inhibitor apremilast in biologic-naïve patients with early peripheral PsA in terms of disease activity, clinical manifestations, patient-perceived outcomes, as well as apremilast's safety profile in routine care settings of Greece. Non-interventional, multicenter, 52-week prospective cohort study, enrolling biologic-naïve patients with early active peripheral PsA who started apremilast after intolerance or inadequate response (within the first 12 months of treatment) to an initial conventional synthetic (cs)DMARD treatment. Non-responder imputation was applied for missing data.In total, 167 consecutive patients (mean age: 52.5 years; median PsA duration: 0.9 years) were analyzed. At baseline, the median (interquartile range) clinical Disease Activity in Psoriatic Arthritis (cDAPSA) score was 22.0 (16.0-29.0), with 86.8% of patients having at least moderate (29.3% high) disease activity; 87.4% had skin psoriasis, 37.7% nail psoriasis, 30.7% enthesitis, and 12.4% dactylitis. At 16, 24, and 52 weeks, 28.7, 42.5, and 48.5% of patients, achieved ≥ 50% improvement in their baseline cDAPSA score, respectively. At week 52, 55.6, 50, and 26.8% of evaluable patients achieved complete resolution of enthesitis, dactylitis and nail psoriasis, respectively. Improvements were also observed in patient's health state assessed by the Psoriatic Arthritis Impact of Disease 12-item questionnaire, and health-related quality of life. The 52-week drug survival rate was 75%, while 13.8% of patients experienced at least one adverse drug reaction.Biologic-naïve patients with early PsA, treated with apremilast experienced significant improvements in disease activity, extra-articular manifestations and patient-centered outcomes, accompanied by a favorable tolerability profile.

Temporal Trends in Multiple Births in Greece: The Evolution of an Epidemic.

Introduction Multiple births constitute the dominant adverse effect of fertility treatments and are associated with increased perinatal risks. The aim of this study was to comprehensively examine and present time trends in multiple births in Greece. Methods Data on live births by multiplicity were derived from the Hellenic Statistical Authority, covering a 65-year period from 1957 to 2021. Temporal trends in multiple birth rates (MBR), twin birth rates (TwBR), as well as in triplet and higher-order birth rates (Tr+BR) were assessed using joinpoint regression analysis, and the annual percentage changes (APC) were calculated with a 95% confidence interval (95% CI) and level of statistical significance (p < 0.05). Results The MBR in Greece showed a downward trend from 1957 to 1979 (APC = -1.7, 95% CI: -2.0 to -1.4, p < 0.001). However, the rate started to climb in the 1980s, accelerated during the 1990s, and continued to rise in the two most recent decades, reaching a historic high and a world record of 57.2 per 1,000 births in 2021, i.e., a 3.4-fold increase since 1985. The TwBR increased from an all-time low of 16.5 per 1,000 births in 1978 with APC = 1.4 (95% CI: 0.2 to 2.5, p = 0.021) during 1979-1989, APC = 6.3 (95% CI: 5.5 to 7.2, p < 0.001) during 1989-2001, and APC = 1.2 (95% CI: 0.8 to 1.5, p < 0.001) during the last two decades (2001-2021). The Tr+BR, after an all-time low of 17.5 per 100,000 births in 1966, increased dramatically from 1982 to 2000 (APC = 12.4, 95% CI: 9.6 to 15.2, p < 0.001), leveled off during 2000-2011, and after reaching a historic maximum of 351.1 per 100,000 births in 2010, there was a sharp decreasing trend during the last decade (2011-2021: APC = -12.1, 95% CI: -16.8 to -7.2, p < 0.001). Conclusion The dramatic increases in maternal age as well as in medically assisted conceptions have resulted in an epidemic increase in MBR in Greece reaching world record levels. During the last decade, there was an encouraging decline in the Tr+BR; however, the TwBR has continued to trend upwards.

Tracing Time Trends of Births in Greece.

Introduction The aim of this study was to comprehensively investigate and present time trends in births in Greece over the last seven decades. Methods Data on live births were derived from the Hellenic Statistical Authority, covering a 72-year period from 1950 to 2021. Trends in the number of births were assessed using joinpoint regression analysis. The annual percentage change (APC) and the average annual percent change (AAPC) were calculated with a 95% confidence interval (95% CI) and level of statistical significance p<0.05. Results The overall trend during 1950-2021 was clearly downward (AAPC = -0.9, 95% CI: -1.2 to -0.7). Over the first three decades, births fluctuated to a record high of 162,839 in 1967, with an overall slight downward trend (1950-1981: APC = -0.2, 95% CI: -0.4 to -0.1, p<0.001). During the 1980 decade, the trend was sharply downward (1981-1988: APC = -4.7, 95% CI: -6.2 to -3.2, p<0.001), followed by a stabilization in the 1990s (1988-2001: APC = -0.1, 95% CI: -0.7 to 0.4, p=0.586). The first decade of the 21st century was the only period during the last seven decades with an increasing trend in births in the Greek population (2001-2008: APC = 1.9, 95% CI: 0.3 to 3.5, p = 0.021), but it was followed by plummeting trends during the recent years (2008-2021: APC = -2.7, 95% CI: -3.2 to -2.3, p<0.001), leading to the historic low of 83,756 births in 2019. Conclusion The time trend analysis of births in Greece indicated a dramatic plummet in natality in Greece, predominantly attributed to the large decline in births in the 1980s, which could not be reversed in the 1990s and 2000s. The recent decrease in births was associated with the financial recession and has put the Greek population in a disastrous low-fertility spiral.

Improving tissue characterization, differentiation and diagnosis in gynecology with the narrow-band imaging technique: A systematic review.

Narrow-band imaging (NBI), an on-demand, real-time endoscopic imaging technique, was developed to enhance visualization of the mucosal vascular network and surface texture. The present article provides a systematic review of studies that assessed the use of NBI in gynecological endoscopy. The following electronic databases were searched: PubMed (1950-2020), Google Scholar (2004-2020) and Cochrane Library (2010-2020). In the initial search, 3,836 entries were identified, of which 31 were finally included in the systematic review. Of the selected studies, 10 (32%) were case reports, 19 (61.2%) were prospective studies and 2 (6.4%) were randomized controlled trials with control groups. The selected studies reported on the use of NBI in hysteroscopy, laparoscopy and colposcopy. It was revealed that NBI utilization in hysteroscopy increased the accuracy, sensitivity and specificity in detecting malignant and premalignant lesions. NBI improved the specificity and sensitivity in the detection of endometriotic lesions and cervical lesions. Conventional white light endoscopy in gynecology may be significantly improved by the use of NBI. Further studies with larger cohorts and improved design are required to achieve more reliable results. It is of special interest that utilization of this method requires apparatus which is expensive; concerns are the long training and experience of staff required and the long learning curve.

Phthalates and fetal growth velocity: tracking down the suspected links.

Fetuses that have not achieved their full growth potential are associated with adverse perinatal and long-term outcomes; thus, it is essential to identify environmental factors that can potentially impair normal intrauterine development. Endocrine disrupting compounds (EDCs), substances capable of altering the homeostasis of the endocrine system, are thought to play a role in restriction of growth velocity, with phthalates being among the most common EDCs to which pregnant women are exposed. Such exposure can potentially lead to changes to the epigenome, placental structure, and hormone function and trigger oxidative stress. Given that these pathways have been linked to fetal growth restriction, we reviewed the literature on the relationship between phthalates and fetal growth. The majority of the studies, which used birth weight as an indicator of intrauterine development, showed contradictory results, the main reason being the EDCs' rapid metabolism. However, we can draw more consistent conclusions when phthalates are quantified at more than one time point during pregnancy. In this narrative review, we present current data indicating the role of phthalates, and especially di-(2-ethylhexyl) phthalate (DEHP), in abnormal fetal growth velocity.

Increased Fibroblast Growth Factor 21 (FGF21) Concentration in Early Second Trimester Amniotic Fluid and Its Association with Fetal Growth.

Altered fetal growth, either reduced or exacerbated, is associated with adverse perinatal outcomes. The underlying pathogenetic mechanisms of altered growth remain unclear. Fibroblast growth factor 21 (FGF21) and insulin are both considered to be major regulators of tissue growth and metabolism. The aim of our study was to investigate the association of second trimester amniotic fluid FGF21 and insulin concentrations with fetal growth. The amniotic fluid concentrations of FGF21 and insulin were determined in 80 cases of different fetal growth patterns (SGA-small for gestational age, LGA-large for gestational age, and AGA-appropriate for gestational age fetuses). Both peptides were found to be increased in cases of abnormal fetal growth, reduced growth velocity (SGA), or macrosomia (LGA). Specifically, FGF21 was significantly increased, as higher FGF21 levels were observed in the amniotic fluid of SGA and LGA fetuses compared with AGA fetuses (p < 0.05). Furthermore, the more severe the fetal smallness, the higher the FGF21 levels (p < 0.05). Similarly, higher insulin levels were noted in the amniotic fluid of SGA and LGA fetuses compared with those in AGA fetuses, though this was not statistically significant (p > 0.05). Again, the more severe the reduced fetal growth, the higher the insulin levels.

Effects of Hormone Therapy and Flavonoids Capable on Reversal of Menopausal Immune Senescence.

Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1ß, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.

A Systematic Review of Bisphenol A from Dietary and Non-Dietary Sources during Pregnancy and Its Possible Connection with Fetal Growth Restriction: Investigating Its Potential Effects and the Window of Fetal Vulnerability.

Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical (EDC), is increasingly hypothesized to be a factor contributing to changes in fetal growth velocity. BPA exposure may be environmental, occupational, and/or dietary, with canned foods and plastic bottles contributing significantly. Our systematic review aims to evaluate the current literature and to investigate the role of BPA in abnormal fetal growth patterns. A search was conducted in the PubMed and Cochrane databases. A total of 25 articles met the eligibility criteria and were included in this systematic review. Eleven of them failed to show a clear relationship between BPA and abnormal fetal growth. The majority of the remaining studies (9/14) found an inverse association of BPA with indicators of fetal growth, whereas three studies suggested increased fetal growth, and two studies produced contradictory findings. Of note, both of the studies that collected a sample (amniotic fluid) directly reflecting BPA concentration in the fetus during the first half of pregnancy revealed an inverse association with birth weight. In conclusion, there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half.