Parental Psychological Distress of Missed Diagnosis of Down Syndrome at Antenatal Screening: A Rare, but Still Real Occurrence - A Case Report and Review of Literature.

INTRODUCTION: Prenatal screening programs are important components for pregnant women care and are often linked with grief and shock based on gestational age or the diagnosis. Lower/no sensitivity is also associated with these screening programs leading to providing false-negative outputs. CASE PRESENTATION: Present work shows a case of missed antenatal diagnosis of Down syndrome and its persistant medical and psychological impact on the family members. We have also discussed the relevant economic and medical-legal issues related to the context and aimed to maintain an adequate awareness among healthcare to discuss properly these investigations (difference between screening and diagnostic testing), their possible outcome (chances of false results) and enabled the pregnant women/couple to take informed decision on early pregnancy. CONCLUSION: These programs are considered as routine clinical practice in many countries from last few years and are necessary to assess the pros and cons of these programs. One of the prime cons involves the likeliness of obtaining a false-negative result due to lack of 100% sensitivity and specificity.

Training in Diagnostic Hysteroscopy: The "Arbor Vitae" Method.

Background and Objectives: Diagnostic hysteroscopy is the gold standard in the diagnosis of intrauterine pathology and is becoming an essential tool in the daily practice of gynecology. Training programs for physicians are necessary to ensure adequate preparation and learning curve before approaching patients. The aim of this study was to describe the "Arbor Vitae" method for training in diagnostic hysteroscopy and to test its impact on the knowledge and skills of trainees using a customized questionnaire. Materials and Methods: A three-day hysteroscopy workshop combining theory and practical "hands on "sessions with dry and wet labs has been described. The aim of the course is to teach indications, instruments, the basic principles of the technique by which the procedure should be performed, and how to recognize and manage the pathologies that can be identified by diagnostic hysteroscopy. To test this training method and its impact on the knowledge and skills of the trainees, a customized 10-question questionnaire was administered before and after the course. Results: The questionnaire was administered to 34 participants. All trainees completed the questionnaire, and no missing responses were recorded. Regarding the characteristics of the participants, 76.5% had less than 1 year of experience in performing diagnostic hysteroscopy and 55.9% reported performing fewer than 15 procedures in their career. For 9 of the 10 questions embedded in the questionnaire, there was a significant improvement in the scores between pre- and post-course, demonstrating a perceived significant improvement in theoretical/practical skills by the trainees. Conclusions: The Arbor Vitae training model is a realistic and effective way to improve the theoretical and practical skills required to perform correct diagnostic hysteroscopy. This training model has great potential for novice practitioners to achieve an adequate level of proficiency before performing diagnostic hysteroscopy on live patients.

Risk factors for non-adherent retained placenta after vaginal delivery: a systematic review.

BACKGROUND: Retained placenta represents a cause of maternal morbidity and mortality affecting 0.5-3% of all vaginal deliveries. The unpredictability of this condition makes difficult to develop predictive and preventive strategies to apply in clinical practice. This analysis collected and analyzed all known risk factors related to this obstetric complication. METHODS: A systematic literature review for all original research articles published between 1990 and 2020 was performed. Observational studies about retained placenta risk factors published in English language were considered eligible. Conference abstracts, untraceable articles and studies focused on morbidly adherent placenta were excluded. The included articles were screened to identify study design, number of enrolled patients and retained placenta risk factors investigated. All stages of the revision followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. RESULTS: Thirty-five studies met the inclusion criteria. The reported retained placenta prevalence ranged from 0.5 to 4.8%. Maternal age, previous cesarean sections, previous dilation and curettage, previous retained placenta, labor induction, resulted as the most recurrent, independent risk factors for retained placenta. Previous estro-progestins therapy, morphological placental features (weight, shape, insertion of umbilical cord, implantation site), endometriosis, Assisted Reproductive Technologies, Apgar score are fascinating new proposal risk factors. CONCLUSIONS: Old and new data are not enough robust to draw firm conclusions. Prospective and well-designed studies, based on a well agreed internationally retained placenta definition, are needed in order to clarify this potential dramatic and life-threatening condition.

Interventions to increase uptake of influenza vaccination in pregnancy: A systematic review and meta-analysis.

BACKGROUND: Maternal influenza vaccination has been introduced in several countries to prevent influenza-related morbidity and mortality in pregnant women, fetuses, and infants too young to be vaccinated. OBJECTIVES: To analyze the available randomized controlled trials (RCTs) on the effectiveness of pregnant women-focused interventions to increase influenza vaccination uptake during pregnancy. SEARCH STRATEGY: Medline, CINAHL, Scopus, Web of Science, and Cochrane Trial were searched on August 25, 2021. SELECTION CRITERIA: RCTs assessing the effectiveness of pregnant women-focused interventions in increasing influenza vaccination among pregnant women were included. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data. A random-effects meta-analysis was conducted to estimate pooled odds ratios (ORs). MAIN RESULTS: Seven RCTs were selected. Overall, the interventions had a significant effect in increasing influenza vaccination during pregnancy compared with standard care (OR 1.78, 95% confidence interval [CI] 1.25-2.54; P = 0.001; I2  = 67%). However, subgroup analysis suggested that influenza vaccination uptake only was associated with educational interventions (OR 2.71, 95% CI 1.93-3.81; P < 0.001; I2  = 0%). CONCLUSIONS: We found that several educational interventions for pregnant women can effectively increase influenza vaccination uptake in this population. Specifically, pamphlets, websites, and brief one-to-one education can be effective tools. REGISTRATION: CRD42021269478.

SARS-CoV-2 Footprints in the Placenta: What We Know after Three Years of the Pandemic.

As the COVID-19 pandemic continues into its third year, there is accumulating evidence on the consequences of maternal infection. Emerging data indicate increased obstetrics risks, including maternal complications, preterm births, impaired intrauterine fetal growth, hypertensive disorders, stillbirth, gestational diabetes, and a risk of developmental defects in neonates. Overall, controversial concerns still exist regarding the potential for vertical transmission. Histopathological examination of the placenta can represent a useful instrument for investigation and can contribute significant information regarding the possible immunohistopathological mechanisms involved in developing unfavorable perinatal outcomes. Based on current evidence, SARS-CoV-2 infection can affect placental tissue by inducing several specific changes. The level of placental involvement is considered one of the determining factors for unfavorable outcomes during pregnancy due to inflammation and vascular injuries contributing to complex cascade immunological and biological events; however, available evidence does not indicate a strong and absolute correlation between maternal infection, placental lesions, and obstetric outcomes. As existing studies are still limited, we further explore the placenta at three different levels, using histology, immunohistochemistry, and molecular genetics to understand the epidemiological and virological changes observed in the ongoing pandemic.

Maternity Blues: A Narrative Review.

Puerperium is a period of great vulnerability for the woman, associated with intense physical and emotional changes. Maternity blues (MB), also known as baby blues, postnatal blues, or post-partum blues, include low mood and mild, transient, self-limited depressive symptoms, which can be developed in the first days after delivery. However, the correct identification of this condition is difficult because a shared definition and well-established diagnostic tools are not still available. A great heterogenicity has been reported worldwide regarding MB prevalence. Studies described an overall prevalence of 39%, ranging from 13.7% to 76%, according to the cultural and geographical contexts. MB is a well-established risk factor for shifting to more severe post-partum mood disorders, such as post-partum depression and postpartum psychosis. Several risk factors and pathophysiological mechanisms which could provide the foundation of MB have been the object of investigations, but only poor evidence and speculations are available until now. Taking into account its non-negligible prevalence after childbirth, making an early diagnosis of MB is important to provide adequate and prompt support to the mother, which may contribute to avoiding evolutions toward more serious post-partum disorders. In this paper, we aimed to offer an overview of the knowledge available of MB in terms of definitions, diagnosis tools, pathophysiological mechanisms, and all major clinical aspects. Clinicians should know MB and be aware of its potential evolutions in order to offer the most timely and effective evidence-based care.

Antenatal Diagnosis and Management of Fetal Intestinal Volvulus: Case Series and Literature Review.

Fetal intestinal volvulus is a rare condition that can lead to hemorrhage, bowel necrosis, and urgent surgical treatment after birth. Thus, prompt diagnosis and treatment are essential to avoiding fetal or neonatal demise. Prenatal ultrasound is a keystone tool in the diagnostic course. However, sonographic findings tend to be non-specific, with limited understanding of the pathophysiology behind their atypical presentation. With a literature review and a case series, we aim to optimize the antenatal diagnosis and management of this rare but life-threatening condition. Six cases from our institution were retrospectively analyzed over 12 years. A literature review was conducted until December 2022. A total of 300 articles matched the keyword "Fetal volvulus", and 52 studies were eligible for the review. Our 6 cases are added to the 107 cases reported in the literature of fetal intestinal volvulus with antenatal ultrasound assessment and without associated gastroschisis or omphalocele. Several prenatal symptoms and ultrasound markers, even if not specific, were more frequently reported. Different experiences of management were described regarding follow-up, the timing of delivery, the mode of delivery, and surgery outcomes. This paper highlights the importance of suspecting and assessing fetal volvulus at routine ultrasound scans, describing the most frequent antenatal presentations and management in order to improve fetal and neonatal outcomes.

(New) antenatal ultrasound signs of fetal junctional epidermolysis bullosa: A case report and systematic review of literature.

Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible.

Precocious Puberty Diagnoses Spike, COVID-19 Pandemic, and Body Mass Index: Findings From a 4-year Study.

Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased. Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years. Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP). Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence (P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values ​​in group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81 hours per day using electronic devices; 88.5% of this group stopped any physical activity. Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors.

COVID-19 vaccination in pregnancy and postpartum.

AIM: To identify whether COVID-19 vaccines should be administered in pregnant and breastfeeding women by reviewing the guidance and other evidence. METHODS: We reviewed the COVID-19 vaccination guidance for pregnant and breastfeeding women published to date and evidence from preclinical experimental and observational clinical studies, and discuss their implications. RESULTS: Pregnant women were excluded from the initial phase 3 clinical trials of COVID-19 vaccines resulting in limited data on their efficacy and safety during pregnancy and postpartum. As a result, since December 2020, there has been conflicting advice from public health, governmental, and professional authorities on this matter. From the end of 2020 up to now, some consensus guidance has been published with a prevalent precautionary approach on the administration of vaccines in pregnant women, in breastfeeding ones, or for those who are planning a pregnancy (either spontaneously or with assisted technologies). After the first few months of vaccine administration in some countries, more permissiveness seems to prevail, although with inconsistencies. At the moment, the results obtained by preclinical experimental and observational clinical studies suggest that the risks of the maternal COVID-19 outweigh the undocumented and hypothetical risks of the COVID-19 vaccines in pregnancy. Also, until two viral vector COVID-19 vaccines were associated with very rare thromboembolic events, all guidance had agreed that all approved COVID-19 vaccines could be administered in pregnancy. Actually, some concern has been expressed. CONCLUSION: COVID-19 vaccines administered in pregnancy can reduce the risk of severe COVID-19 and their serious consequences for mothers and their offspring. However, many aspects remain to be clarified.

COVID-19 vaccination in pregnancy and postpartum.

Pregnant women were excluded from the initial phase 3 clinical trials of COVID-19 vaccines resulting in limited data on their efficacy and safety during pregnancy and postpartum. As a result, since December 2020, there has been conflicting advice from public health, governmental, and professional authorities on this matter. From the end of 2020 up to now, some consensus guidance has been published with a prevalent precautionary approach on the administration of vaccines in pregnant women, in breastfeeding ones, or for those who are planning a pregnancy (either spontaneously or with assisted technologies). After the first few months of vaccine administration in some countries, more permissiveness seems to prevail, although with inconsistencies. Some little indicative advice, their inconsistency around the world and their changes in a short time have probably disoriented both women and their health care providers and placed the burden of decision making upon women and their health care providers without information to assist in making an informed choice. We reviewed the COVID-19 vaccination guidance for pregnant and breastfeeding women published to date and evidence from cases of unplanned pregnancy during the course of vaccine trials, preclinical experimental and observational clinical studies, and discuss their implications. In this way, we have tried to identify the safety of COVID-19 vaccines for pregnant or breastfeeding women, and their offspring.

Food insecurity, food deserts, reproduction and pregnancy: we should alert from now.

Food insecurity and food deserts are prominent global health problems, now exacerbated by current COVID-19 pandemic. Some evidence points to the importance of food security, particularly for women in their reproductive age. Women's health and their nutrition status, across the continuum of preconception to pregnancy and postpartum are critical aspects for ensuring positive gestation course and short-/long-term outcomes by affecting essential developmental pathways. Several adverse outcomes (both maternal and neonatal) were reported in scientific literature. Screening programs, new economic policies, implementation of assistance since preconception could be a good strategy to mitigate the negative consequences of food insecurity. Potential strategies could include addressing misconceptions about healthy maternal diet and breast milk adequacy, stress management, promote social support networks, and connecting to supplemental nutrition assistance programs.KEY POINTSFood insecurity (limited food access owing to cost) and desert foods (living in areas with low physical/personal access to nutritious food) are major public health concerns.Large geographical and within-country disparities, multiple socio-economic determinants.Childbearing age and pregnancy are groups at higher vulnerability to develop complications.Food insecurity negatively affects offspring health and development.Peri-conceptional window: an early clinical opportunity to screen and to apply preventive strategies.Help vulnerable groups to have access to more affordable nutritious food, educate and change unhealthy behaviors, adequate stress management, social support networks.

Endometrial receptivity and pregnancy outcome.

Human implantation is a highly complex and multifactorial process. Successful implantation requires the presence of a healthy embryo, a receptive endometrium, and a synchronized molecular dialogue between the two, as well as immune tolerance/protection from the host. The endometrial receptivity refers to a hormonally limited period in which the endometrial tissue acquires a transient functional status allowing blastocyst implantation and pregnancy initiation. Global knowledge of endometrial receptivity grew up in recent years. Improvements in genetics, new biomarkers, noninvasive methods, new advanced techniques (Endometrial receptivity assay - the ERA system, proteomic analysis) offer the possibility to evaluate the endometrial status and to manage patients with infertility problems, especially women undergoing assisted reproductive treatment. This overview reports the most relevant knowledge and recent advances in the study of implantation processes from the perspective of the endometrium, often considered as being the main barrier for a successful pregnancy initiation. Endometrial receptivity is a topic of great interest and further studies are needed for the early identification of endometrial abnormalities and the discovery of new strategies for increasing the chance for the establishment of pregnancy.

Obstetrical complications and outcome in patients with endometriosis.

Endometriosis is a disease that has a profound impact on the quality of life of women, due to the associated chronic pelvic pain, dysmenorrhea, dyspareunia and infertility. However, even getting long-awaited pregnancy (often after assisted reproductive technologies), patients with endometriosis have a high risk of obstetric complications, such as miscarriage, preterm birth, preeclampsia, placental abnormalities, hemorrhage in labor, birth of small for gestational age infants, stillbirth and higher cesarean section rate. In addition, during pregnancy acute complications of endometriosis may occur, such as spontaneous hemoperitoneum, which is rare but life-threatening conditions that in most cases require surgical intervention. The mechanisms of the observed complications in pregnant women with endometriosis are not fully understood. This review presents literature data and personal considerations on the effect of endometriosis on pregnancy outcome and the occurrence of complications, as well as their possible underlined mechanisms. Based on this, we proposed ways to reduce the risk of obstetric complications in pregnant women with a history of endometriosis.

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) and influenza immunization: an overview.

BACKGROUND: Maternal tetanus, diphtheria, and acellular pertussis (Tdap) and influenza immunization for women during pregnancy (the so-called "maternal immunization") has been introduced in several countries, and recently also in Italy, to protect mother and fetus during pregnancy, infant in his first months of life and mother during postpartum period. However, very low vaccination coverage rates have been reached due to several variables. METHODS: A literature search was conducted on PubMed and Embase, including any experimental or observational studies, to assesses existing evidence on the effectiveness, efficacy, safety and optimal timing of administration of Tdap and influenza immunization in pregnancy for mothers and their infants. The search was finalized in August 2019. RESULTS: Reviewing the literature, we identified only a few studies that, among several maternal and infant outcomes, found sporadic significant associations with maternal influenza immunization and even less with Tdap immunization. Moreover, most of the authors of these studies explained these findings as a result of residual confounding effect. The effectiveness of maternal influenza immunization is more complicated to prove than the effectiveness of Tdap immunization because of several reasons. Not all nations recommend and offer vaccines in the same weeks of pregnancy and this one manifests the complexity in defining the best timing for Tdap or influenza immunization. CONCLUSIONS: The safety of maternal Tdap or influenza immunization is supported by the evidence so far, however, regular surveillance should be maintained, especially with regard to the influenza vaccine that changes in formulation each year. There is a need to optimize the timing of vaccination in pregnancy and to have a national system of detection of maternal immunization in each country.

Prevention of Preterm Birth with Progesterone.

Gestational age at birth is a critical factor for perinatal and adulthood outcomes, and even for transgenerational conditions' effects. Preterm birth (PTB) (prematurity) is still the main determinant for infant mortality and morbidity leading cause of infant morbidity and mortality. Unfortunately, preterm birth (PTB) is a relevant public health issue worldwide and the global PTB rate is around 11%. The premature activation of labor is underlined by complex mechanisms, with a multifactorial origin influenced by numerous known and probably unknown triggers. The possible mechanisms involved in a too early labor activation have been partially explained, and involve chemokines, receptors, and imbalanced inflammatory paths. Strategies for the early detection and prevention of this obstetric condition were proposed in clinical settings with interesting results. Progesterone has been demonstrated to have a key role in PTB prevention, showing several positive effects, such as lower prostaglandin synthesis, the inhibition of cervical stromal degradation, modulating the inflammatory response, reducing gap junction formation, and decreasing myometrial activation. The available scientific knowledge, data and recommendations address multiple current areas of debate regarding the use of progesterone in multifetal gestation, including different formulations, doses and routes of administration and its safety profile in pregnancy.

Fetal transient tricuspid valve regurgitation: sonographic features and clinical evolution.

PURPOSE: To analyze the prevalence, the sonographic features, the clinical evolution and significance of fetal tricuspid valve regurgitation (TR). STUDY DESIGN: This is a prospective study. Serial ultrasound examinations were performed at 20-23, at 26-29 and at 30-34 gestational weeks in 675 consecutive singleton pregnancies with fetal normal growth and normal cardiac anatomy. The fetal tricuspid valve regurgitation was classified according to its duration, to the peak of jet maximum velocity and to its maximum spatial extension. A clinical examination and echocardiography were performed in neonates after birth. RESULTS: During the first examination (20-23 weeks), 32 cases of tricuspid valve regurgitation were identified. The prevalence of tricuspid regurgitation was 4.74%. The large majority of TR cases were not-holosystolic (87.5%), with a maximum velocity below 2 m/sec (80-130 cm/sec in 84% cases and 180-200 cm/sec in 16% cases) and with a little spatial extension (type I or II in 87.5% cases). Following this hemodynamic phenomenon during the following weeks, we found that it disappeared around 29 weeks in all cases. CONCLUSIONS: Tricuspid regurgitation observed during the second trimester can be considered a transient and functional hemodynamic phenomenon, without apparent pathological significance.

The effect of prenatal exposure to music on fetal movements and fetal heart rate: a pilot study.

OBJECTIVE: To assess and compare fetal cardiac parameters of fetuses listening to music before and during nonstress test, only during the test or never. STUDY DESIGN: Thirty healthy mother-fetus dyads were randomized in a 1:1:1 ratio to one of three groups: group A in which fetuses were submitted to prelistening phase (33rd + 0 to 36th + 3 week) and listening sessions during 4 nonstress tests, group B in which fetuses were submitted to listening sessions during 4 nonstress tests, and group C receiving 4 nonstress tests without any listening. We assessed mean fetal heart rate, fetal heart rate accelerations, fetal heart rate decelerations, fetal movements and uterine contractility. RESULTS: Fetuses of the group A, who had already listened to a particular piece of music during previous sessions, had significantly increased their heart rate accelerations and movements during the music listening session of the last nonstress test. No significant changes were observed in the number of uterine contractions. CONCLUSIONS: Our findings show that fetuses slightly respond to that music they know, but they do not significantly respond to unknown music.

Progesterone: History, facts, and artifacts.

Progesterone and its related molecules are a crucial tool in modern clinical practice, particularly in the fields of reproductive medicine. Its history is old, but still under development. Presently, the pharmacokinetic and pharmacodynamic profiles of progesterone is well-known and knowledge on natural progesterone (P4) and other molecules with progestational activity, namely progestogens or gestagens, are improved and their interest is still alive. Topics of great and current interest are progesterone and its role in assisted reproductive protocols, threatened and recurrent pregnancy loss, threatened preterm birth with favorable results on pregnancy, and perinatal outcomes. Moreover, progesterone provides several other positive effects on women's health. This paper describes the main chronological steps that characterized the history of progesterone, where scientific research and clinical practice are arrived and WHICH are the future perspectives on this hormone with a "never-ending history."

The biological basis and prevention of preterm birth.

The time of birth is a critical determinant of perinatal and long-term outcomes. Preterm birth is still the first cause of infant mortality and morbidity; unfortunately, rates of preterm birth remain high in both high- and low-resource countries, ranging from 5% to 18%. Preterm parturition is a syndrome, which can be induced by various factors such as infection, cervical pathology, uterine overdistension, progesterone deficiency, vascular alterations (utero-placental ischemia, decidual hemorrhage), maternal and fetal stress, allograft reaction, allergic phenomena, and probably other several unknown factors. These various etiologies can lead to the pathological activation of a common pathway of decidua/fetal membranes, which causes uterine contractility, cervical ripening, and rupture of membranes. Moreover, the mechanisms responsible for these processes have been identified, which involve receptors, chemokines, and inflammatory cytokines. It is very important to understand the cellular and biochemical pathways responsible for preterm labor to identify, treat, and prevent negative outcome in a timely manner. Clinicians and researchers play a key role in improving biochemical knowledge on preterm delivery, identifying risk factors, and shaping interventions that can address this complex syndrome.