MRI Assessed Placental Location as a Diagnostic Tool of Placental Invasiveness and Maternal Peripartum Morbidity.

Placenta accreta spectrum (PAS) disorder is one of the leading causes of peripartum maternal morbidity and mortality; its early identification during pregnancy is of utmost importance to ensure the optimal clinical outcome. The aim of the present study is to investigate the possible association of the presence and type/location of placenta previa on MRI with PAS and maternal peripartum outcome. One hundred eighty-nine pregnant women (mean age: 35 years; mean gestational age: 32 weeks) at high risk for PAS underwent a dedicated placental MRI. All women underwent a C-section within 6 weeks from the MRI. All MRIs were evaluated by two experienced genitourinary radiologists for presence, type (complete/partial vs. marginal/low lying), and location (anterior vs. anterior-posterior vs. posterior) of placenta previa. Statistical analysis was performed for possible association of type/location of previa with placental invasiveness and peripartum outcomes. Intraoperative information was used as a reference standard. Complete/partial previa was detected in 143/189 (75.6%) and marginal/low lying previa in 33/189 (17.5%) women; in 88/189 (46.6%) women, the placenta had anterior-posterior, in 54/189 (28.6%) anterior and in 41/189 (21.7%) posterior. Complete/partial previa had an at least 3-fold probability of invasiveness and was more frequently associated with unfavorable peripartum events, including massive intraoperative blood loss or hysterectomy, compared to low-lying/marginal placenta. Posterior placental location was significantly associated with lower rates of PAS and better clinical outcomes. In conclusion, the type and location of placenta previa shown with MRI seems to be associated with severity of complications during delivery and should be carefully studied.

Breaking Bad News During Prenatal Screening: The Role of Professional Obstetricians and Midwives in Greece.

INTRODUCTION: Breaking bad news is one of the most difficult responsibilities in medical practice. Although medical staff in clinical practice often encounter situations that necessitate the announcement of unpleasant news, there is a lack of training regarding their communication with patients and their families. Effective interaction between medical staff and pregnant women constitutes a crucial component of breaking down unpleasant news. This research aimed to investigate the knowledge and attitude of health professionals, particularly obstetricians, and midwives, regarding the announcement of bad news during prenatal screening. METHODS: The study was conducted between September 2017 and April 2018. One hundred professional obstetricians and midwives involved in fetal and prenatal medicine in Greece were part of the study. The study consisted of two parts: the first covered the emotional state of healthcare professionals during the announcement of unpleasant news, and the second covered the appropriate way to inform unpleasant results during prenatal testing. RESULTS: In this study, only 41% of the participants considered that they felt comfortable discussing issues related to the diagnosis of an unpleasant result during prenatal testing with the pregnant woman/patient, or her relatives, and 85% accepted that they had experienced feelings of sadness, anxiety, or guilt when announcing unpleasant results. Furthermore, 87% of the participants believed that the non-verbal communication component (eye contact, body language) plays an important role in breaking bad news. Finally, 65% considered that prolonged monitoring of the ultrasound screen during prenatal screening does not increase the anxiety of pregnant women when carried out for a better medical opinion. CONCLUSIONS: Delivering bad news during prenatal screening creates stress for the parents. As far as the ethical, cultural, psychological, and legal complicity of healthcare professionals is concerned, communicating unpleasant news has been a subject of discussion by many experts. It is important to understand the concerns of women regarding the risks of counseling.

Prenatal diagnosis of 18p deletion and 8p trisomy syndrome: literature review and report of a novel case.

18p deletion syndrome constitutes one of the most frequent autosomal terminal deletion syndromes, affecting one in 50,000 live births. The syndrome has un-specific clinical features which vary significantly between patients and may overlap with other genetic conditions. Its prenatal description is extremely rare as the fetal phenotype is often not present during pregnancy. Trisomy 8p Syndrome is characterized by heterogenous phenotype, with the most frequent components to be cardiac malformation, developmental and intellectual delay. Its prenatal diagnosis is very rare due to the unspecific sonographic features of the affected fetuses. We present a very rare case of a fetus with multiple anomalies diagnosed during the second trimester whose genomic analysis revealed a 18p Deletion and 8p trisomy Syndrome. This is the first case where this combination of DNA mutations has been described prenatally and the second case in general. The presentation of this case, as well as the detailed review of all described cases, aim to expand the existing knowledge regarding this rare condition facilitating its diagnosis in the future.

Visceral Leishmaniasis in a Twin Pregnancy: A Case Report and Review of the Literature.

Visceral leishmaniasis (VL), often referred to as kala-azar, is quite rare in developed countries during pregnancy. Only few studies have evaluated its impact on perinatal outcome. It is caused primarily by Leishmania donovani or Leishmania infantum and presents with a wide spectrum of clinical manifestations from cutaneous ulcers to multisystem disease. Differential diagnosis is challenging as symptoms and signs are insidious, mimicking other diseases. Misdiagnosis can result in severe adverse perinatal outcomes, even maternal/neonatal death. Early treatment with liposomal amphotericin-B (LAmB) is currently the first choice with adequate effectiveness. We report a rare case of VL in a twin pregnancy with onset at the second trimester, presenting with periodic fever with rigors, right flank pain, and gradual dysregulation of all three cell lines. The positive rK39 enzyme-linked immunosorbent assay test confirmed the diagnosis. Treatment with LAmB resulted in clinical improvement within 48 h and in the delivery of two late-preterm healthy neonates with no symptoms or signs of vertical transmission. The one-year follow-up, of the mother and the neonates, was negative for recurrence. To our knowledge, this is the first reported case of VL in a twin pregnancy, and consequently treatment and perinatal outcome are of great importance.

The Effect of Maternal Diet and Physical Activity on the Epigenome of the Offspring.

The aim of this review was to examine the current literature regarding the effect of maternal lifestyle interventions (i.e., diet and physical activity) on the epigenome of the offspring. PubMed, Scopus and Cochrane-CENTRAL were screened until 8 July 2023. Only randomized controlled trials (RCTs) where a lifestyle intervention was compared to no intervention (standard care) were included. Outcome variables included DNA methylation, miRNA expression, and histone modifications. A qualitative approach was used for the consideration of the studies' results. Seven studies and 1765 mother-child pairs were assessed. The most common types of intervention were dietary advice, physical activity, and following a specific diet (olive oil). The included studies correlated the lifestyle and physical activity intervention in pregnancy to genome-wide or gene-specific differential methylation and miRNA expression in the cord blood or the placenta. An intervention of diet and physical activity in pregnancy was found to be associated with slight changes in the epigenome (DNA methylation and miRNA expression) in fetal tissues. The regions involved were related to adiposity, metabolic processes, type 2 diabetes, birth weight, or growth. However, not all studies showed significant differences in DNA methylation. Further studies with similar parameters are needed to have robust and comparable results and determine the biological role of such modifications.

Screening for perinatal depression and stress: a prospective cohort study.

PURPOSE: There is currently a heightened need for perinatal medical services to timely recognize and accurately meet the psychological needs of pregnant women. Psychological disturbances a mother experiences during pregnancy, such as depression and anxiety, can be later associated with inadequate maternal capacity for antenatal care for herself and the baby, and may lead to subsequent mental health problems later in the mother's life. Routine prenatal assessment could significantly benefit from being proactively enriched with early prevention mental health screening tools to assess, appropriately manage vulnerable populations, and subsequently implement preventive actions. METHODS: 178 pregnant women, under routine prenatal medical assessment, were measured regarding depressive symptomatology and stress, through the use of two validated psychometric tools (the Edinburgh Postnatal Depression Scale (EPDS) and the Perceived Stress Scale (PSS-14)). RESULTS: Heightened perceived stress and depressive symptomatology levels were associated with younger maternal age, an obstetrical record of more than one births and a history of abortion. Results additionally showed a connection between the requirement for a psychiatric referral-based on the levels of symptomatology recorded through the psychometric assessment and a clinical interview-and currently running the earlier stages (weeks) of pregnancy. CONCLUSION: Our revised proposed prenatal screening protocol for depression and stress suggests an amplified follow-up assessment including all pregnant women scoring high in both depression and in perceived stress, regardless of previous history of prenatal depression or of suicidality, to detect earlier or less manifest expressions of distress during pregnancy, in vulnerable perinatal populations.

Uterine Arteries Resistance in Pregnant Women with Gestational Diabetes Mellitus, Diabetes Mellitus Type 1, Diabetes Mellitus Type 2, and Uncomplicated Pregnancies.

BACKGROUND: The examination of the uterine arteries using Doppler in the first trimester of pregnancy serves as a valuable tool for evaluating the uteroplacental circulation. Diabetes mellitus is associated with altered placental implantation and pregnancy-related pathologies, such as preeclampsia. The aim of this study was to compare the uterine arteries' pulsatility indices (UtA PI) in women with diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), gestational diabetes mellitus (GDM), and uncomplicated pregnancies. METHODS: This was a retrospective case-control trial including pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, presenting for first-trimester ultrasound screening in two tertiary university hospitals between 2013 and 2023. The first-trimester UtA pulsatility index (PI), expressed in multiples of medians (MoMs), was compared between the four groups. RESULTS: Out of 15,638 pregnant women, 58 women with DM1, 67 women with DM2, 65 women with GDM, and 65 women with uncomplicated pregnancies were included. The mean UtA PI were 1.00 ± 0.26 MoMs, 1.04 ± 0.32 MoMs, 1.02 ± 0.31 MoMs, and 1.08 ± 0.33 MoMs in pregnant women with DM1, DM2, GDM, and uncomplicated pregnancies, respectively (p > 0.05). CONCLUSIONS: Potential alterations in the implantation of the placenta in pregnant women with diabetes were not displayed in the first-trimester pulsatility indices of the uterine arteries, as there were no changes between the groups.

Pregnancy outcomes in the different phenotypes of gestational diabetes mellitus based on the oral glucose tolerance test. A systematic review and meta-analysis.

AIMS: To assess the prevalence variation in pregnancy outcomes of the different phenotypes of gestational diabetes mellitus (GDM). MATERIALS: Cohort, cross sectional and case control studies grouping together pregnant women with GDM, based on the results of oral glucose tolerance test(OGTT) and reporting pregnancy outcomes in each group, were included. The primary outcomes were (i)large for gestational age and ii)hypertensive disorders of pregnancy (HDP). The secondary outcomes included (i)insulin treatment, ii)admission to neonatal intensive care unit, iii)preterm birth, iv)small for gestational age and v)caesarean section. The pooled proportions of the outcomes of interest were calculated for each phenotype. RESULTS: 8 studies (n = 20.928 women with GDM) were included. The pooled prevalence of LGA, HDP and insulin treatment were 20 %, 8 % and 24 % respectively in women with abnormal fasting plasma glucose,10 %, 6 % and 9 % respectively in women with abnormal post-load plasma glucose and 14 %,14 % and 30 % in women with abnormal combined plasma glucose. CONCLUSIONS: Pregnant women with abnormal fasting plasma glucose, present with the highest prevalence of LGA, while those with abnormal combined plasma glucose, present with the highest prevalence of HDP. Pregnant women with abnormal post-load plasma glucose present with the lowest need for insulin treatment.

Tumor Markers and Their Diagnostic Significance in Ovarian Cancer.

Ovarian cancer (OC) is characterized by silent progression and late-stage diagnosis. It is critical to detect and accurately diagnose the disease early to improve survival rates. Tumor markers have emerged as valuable tools in the diagnosis and management of OC, offering non-invasive and cost-effective options for screening, monitoring, and prognosis. PURPOSE: This paper explores the diagnostic importance of various tumor markers including CA-125, CA15-3, CA 19-9, HE4,hCG, inhibin, AFP, and LDH, and their impact on disease monitoring and treatment response assessment. METHODS: Article searches were performed on PubMed, Scopus, and Google Scholar. Keywords used for the searching process were "Ovarian cancer", "Cancer biomarkers", "Early detection", "Cancer diagnosis", "CA-125","CA 15-3","CA 19-9", "HE4","hCG", "inhibin", "AFP", "LDH", and others. RESULTS: HE4, when combined with CA-125, shows improved sensitivity and specificity, particularly in early-stage detection. Additionally, hCG holds promise as a prognostic marker, aiding treatment response prediction and outcome assessment. Novel markers like microRNAs, DNA methylation patterns, and circulating tumor cells offer potential for enhanced diagnostic accuracy and personalized management. Integrating these markers into a comprehensive panel may improve sensitivity and specificity in ovarian cancer diagnosis. However, careful interpretation of tumor marker results is necessary, considering factors such as age, menopausal status, and comorbidities. Further research is needed to validate and refine diagnostic algorithms, optimizing the clinical significance of tumor markers in ovarian cancer management. In conclusion, tumor markers such as CA-125, CA15-3, CA 19-9, HE4, and hCG provide valuable insights into ovarian cancer diagnosis, monitoring, and prognosis, with the potential to enhance early detection.

Short- and Long-Term Outcomes of Preeclampsia in Offspring: Review of the Literature.

Preeclampsia is a multisystemic clinical syndrome characterized by the appearance of new-onset hypertension and proteinuria or hypertension and end organ dysfunction even without proteinuria after 20 weeks of pregnancy or postpartum. Residing at the severe end of the spectrum of the hypertensive disorders of pregnancy, preeclampsia occurs in 3 to 8% of pregnancies worldwide and is a major cause of maternal and perinatal morbidity and mortality, accounting for 8-10% of all preterm births. The mechanism whereby preeclampsia increases the risk of the neurodevelopmental, cardiovascular, and metabolic morbidity of the mother's offspring is not well known, but it is possible that the preeclamptic environment induces epigenetic changes that adversely affect developmental plasticity. These developmental changes are crucial for optimal fetal growth and survival but may lead to an increased risk of chronic morbidity in childhood and even later in life. The aim of this review is to summarize both the short- and long-term effects of preeclampsia on offspring based on the current literature.

Investigating the Link between Early Life and Breast Anomalies.

Several factors during childhood and adolescence are thought to be associated with the development of proliferative benign breast diseases and breast cancer in adulthood. In order to identify them, the authors conducted an extensive review of the literature up to October 2022, searching for clinical studies, reports, and guidelines in English. A thorough Medline/Pubmed and Google scholar database research was performed, investigating the link between diet, exercise, age of menarche, body mass index, ionizing radiation exposure during childhood and adolescence, and proliferative breast diseases and breast cancer in adulthood. A list of keywords, including breast disorders, adolescence, childhood, and breast cancer was included in our search algorithm. Numerous studies concede that the development of breast disease in adulthood is influenced by various risk factors, whose influence begins during early childhood and adolescence.

Prevalence of preeclampsia and uterine arteries resistance in the different phenotypes of gestational diabetes mellitus.

AIMS: This study aims to investigate the different phenotypes of Gestational Diabetes Mellitus (GDM), in correlation to preeclampsia and uterine arteries resistance. MATERIALS: This is a prospective cohort study including women with and without GDM per the IADPSG criteria. Three phenotypes of GDM emerged, women with only abnormal fasting (AF) glucose levels, women with only abnormal post-load (AP) glucose levels at 60' and/or 120' and women with abnormal combined (AC) fasting and post-load glucose values. All women underwent uterine arteries doppler examination in the three trimesters and assessed for preeclampsia development. Linear regression was used to express the trajectories of uterine arteries resistance throughout the pregnancy. RESULTS: 6928 pregnant women were included, 5274 without GDM and 1654 with GDM. 546, 781 and 327 of GDM pregnancies presented with AF, AP and AC phenotypes respectively. Prevalence of preeclampsia was 17.9%, 26.8% and 30% in the AF, AP and AC phenotypes respectively (p < 0.001). In women who developed preeclampsia, AC phenotype presented with statistically different trajectory of Uterine Arteries Pulsatility Index Percentiles b = 0.129 than women without GDM and women with AP GDM phenotype b = -0.015 and b = -0.016 respectively. CONCLUSIONS: The combined abnormal phenotype presents with the highest rate of preeclampsia and the most distinct pattern of uterine arteries resistance.

Prenatal Identification of a Novel Mutation in the MCPH1 Gene Associated with Autosomal Recessive Primary Microcephaly (MCPH) Using Next Generation Sequencing (NGS): A Case Report and Review of the Literature.

BACKGROUND: MCPH1 is known as the microcephalin gene (OMIM: *607117), of which the encoding protein is a basic regulator of chromosome condensation (BCRT-BRCA1 C-terminus). The microcephalin protein is made up of three BCRT domains and conserved tandem repeats of interacting phospho-peptides. There is a strong connection between mutations of the MCPH1 gene and reduced brain growth. Specifically, individuals with such mutations have underdeveloped brains, varying levels of mental retardation, delayed speech and poor language skills. METHODS: In this article, a family with two affected fetuses presenting a mutation of the MCPH1 gene is reported. During the first trimester ultrasound of the second pregnancy, the measure of nuchal translucency was increased (NT = 3.1 mm) and, therefore, the risk for chromosomal abnormalities was high. Chorionic villi sampling (CVS) was then performed. Afterwards, fetal karyotyping and Next Generation Sequencing were carried out. Afterwards, NGS was also performed in a preserved sample of the first fetus which was terminated due to microcephaly. RESULTS: In this case, the fetuses had a novel homozygous mutation of the MCPH1 gene (c.348del). Their parents were heterozygous for the mutation. The fetuses showed severe microcephaly. Because of the splice sites in introns, this mutation causes the forming of dysfunctional proteins which lack crucial domains of the C-terminus. CONCLUSION: Our findings portray an association between the new MCPH1 mutation (c.348del) and the clinical features of autosomal recessive primary microcephaly (MCPH), contributing to a broader spectrum related to these pathologies. To our knowledge, this is the first prenatal diagnosis of MCPH due to a novel MCPH1 mutation.

Screening vs. no screening for preterm delivery in low-risk singleton pregnancies: comparison by propensity score analysis.

PURPOSE: To compare the effect of a policy of screening for spontaneous preterm delivery (SPD) by transvaginal cervical length (CL) measurement versus a no screening policy in the prevention of severe prematurity. METHODS: Retrospective study on low-risk singleton pregnancies examined at 20-24 weeks. Two cohorts, one with SPD screening and the other without screening, were matched using propensity analysis to create the study groups. Women with short CL were treated with vaginal progesterone and/or cervical cerclage/pessary. The outcomes examined were SPD < 32 weeks (SPD 32) and SPD between 20 and 32 weeks (SPD 20-32). RESULTS: Screening for SPD was associated with a significant reduction in the rate of SPD at less than 32 weeks (0.3 vs. 0.8%, p = 0.001 in the screened and no screened pregnancies, respectively) and in the rate of SPD 20-32 (0.3 vs. 0.9%, p = 0.005 in the screened and no screened pregnancies, respectively). After adjusting for maternal age, parity, body mass index, smoking and mode of conception, the screening group had significantly lower hazard for SPD 20-32 (HR = 0.36, 95% CI: 0.18-0.75, p = 0.006) and SPD32 (HR = 0.39, 95% CI: 0.19-0.82, p = 0.013). CONCLUSION: Screening for SPD by transvaginal CL measurement in mid-pregnancy may reduce the incidence of severe prematurity in low-risk singleton pregnancies.

Conjoined Twins Complicating a Dichorionic Triplet Pregnancy after Intracytoplasmic Sperm Injection: A Case Report and Review of the Literature.

Conjoined twins represent a rare type of monoamniotic twins. Ultrasound assessment during the first trimester can facilitate the diagnosis, however further assessment by colour Doppler studies, 3D imaging, fetal echocardiography and fetal magnetic resonance imaging (MRI) is usually required in order to determine the specific fetal abnormalities and to guide appropriate pregnancy management. This case report presents a rare case of conjoined twins complicating a dichorionic-diamniotic triplet pregnancy, achieved after intracytoplasmic sperm injection (ICSI) and blastocyst transfer. A 44-year-old woman was referred for chorionicity determination to our Fetal Medicine Centre due to suspicion of conjoined twins in a triplet pregnancy. Ultrasound assessment at 11 weeks demonstrated a dichorionic triplet pregnancy which was also complicated by a rare type of conjoined twins (thoracoomphalopagus) and after a successful embryo reduction a neonate of 2200 g was delivered by caesarean section at term. The accurate diagnosis and early detection of conjoined twins by a fetal medicine specialist is crucial, especially as far as multiple pregnancies with three or more fetuses are concerned.

The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis.

Controlled ovarian hyperstimulation (COH) is essential for the success of in vitro fertilization (IVF). Evidence showing the comparison of different COH protocols remains predominantly of low certainty and derives from unspecified infertile and highly heterogeneous populations. Thus, personalized approaches to examine the response of patients to the various COH protocols need to be investigated. Data from in vitro and animal studies have identified the mechanistic target of rapamycin (mTOR) and Hippo signaling pathways play a key role in follicular homeostasis and oocyte quality. To be specific, current data indicate the controlled activation of mTOR and the controlled inhibition of the Hippo pathway within the ovarian granulosa cells (GC). Both are reported to lead to a nurturing follicular microenvironment, increase oocyte quality, and potentially improve reproductive outcomes. As intracellular markers, phosphorylated/unphosphorylated levels of the pathways' main downstream mediators could be included among the candidate "personalized" predictors of patients' response to COH protocols and final IVF outcomes. Based on these hypotheses, we make a preliminary attempt to investigate their validity: We propose a prospective cohort study to compare the levels of certain phosphorylated/unphosphorylated components of the investigated pathways (mTOR, ribosomal protein S6 kinase beta-1 (p70S6K-1), yes-associated protein-1 (YAP-1), and transcriptional coactivator with PDZ-binding motif (TAZ)) within the follicular fluid-isolated GC between women undergoing gonadotropin-releasing hormone (GnRH) antagonist/"short" protocols and those receiving GnRH agonist/"long 21" protocols. A case-control design comparing these levels between women achieving pregnancy and those who did not is further planned. Additional analyses addressing the population's expected heterogeneity are planned after the completion of the pilot phase, during which 100 participants undergoing IVF are intended to be recruited. At this stage, these hypotheses are solely based on in vitro/animal data, and thus, similar studies on humans in this respect are necessary for the investigation of their potential validity.

Daughters of polycystic ovary syndrome pregnancies and androgen levels in puberty: a Meta-analysis.

Purpose: To provide an overview and critical analysis of the literature related to the circulating androgen levels of daughters of PCOS mothers during prepubertal and pubertal stage who have not yet been diagnosed with PCOS or precocious puberty. Methods: We critically considered and meta-analyzed observational studies comparing androgens concentration in daughters of PCOS mothers compared to daughters of mothers without PCOS. A literature search was conducted in MEDLINE, Scopus and other sources from 01/09/2021 until 01/12/2021. The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The primary outcome included total testosterone levels whereas the secondary outcomes included 17a-hydroxyprogesterone (17-OHP), androstenedione (Δ4Α) and Sex Hormone Binding Globulin (SHBG) levels respectively. Results: Our search yielded 1073 studies, 9 of which were included in our analysis. The results are presented differently according to pubertal stage. Pubertal daughters of PCOS mothers exhibited significantly higher total testosterone (pooled mean difference 14.95 (95%CI: 6.98 to 22.93), higher 17-OHP (pooled mean difference 0.11 (95%CI: 0.02 to 0.20) and lower SHBG levels (pooled mean difference -10.48 (95%CI: -16.46 to -4.61). Instead, prepubertal daughters of PCOS mothers presented greater SHBG levels (pooled mean difference 7.79 (95%CI: 0.03 to 15.54) compared to controls. No difference was found in Δ4Α levels in both groups. Conclusion: The onset of puberty is a critical point in the development of the disease and an early intervention may be imperative.

Familial Aggregation of a Novel Missense Variant of COL2A1 Gene Associated with Short Extremities: Case Report and Review of the Literature.

We present two cases of family members (first cousins) with short extremities caused by a novel variant of COL2A1 gene (NM_001844.5). Case 1 description: A 29-year-old woman presented in her first pregnancy for a second trimester anomaly scan at 23 weeks of gestation. Fetal long bones were measured below the third centile for gestational age. Follow-up scans revealed fetal long bone growth deceleration. Initial genetic work-up was negative and the rest of the maternal follow-up was unremarkable. A male baby weighing 3180 g was delivered at 39 weeks and 4 days of gestation. Case 2 description: A 33-year-old pregnant woman presented for a routine second trimester anomaly scan at 20 weeks and 4 days of gestation. All fetal measurements were appropriate for the gestational age. The routine growth scan performed at 32 weeks showed fetal long bone measurements below the third centile for gestational age, while the follow-up growth scan at 36 weeks and 4 days of gestation revealed consistent, below the third centile, fetal long bone growth. Given that the fetuses of these two cases were related (first cousins), whole exome sequencing (WES) was performed on Case 2. WES revealed a novel heterozygous missense variant c.1132G>A (p. Gly378Ser) of COL2A1 gene (NM_001844.5). Subsequently, targeted genetic sequencing for the variant was performed on Case 1 and the same novel variant was found. Targeted sequencing revealed the same variant in the mother of Case 1 and the father of Case 2 (siblings). A female baby weighing 3200 g was delivered at 40 weeks and 4 days of gestation.

Associations between Maternal and Offspring Hair Cortisol Concentrations and Child Behavioral Symptoms in Mother-Child Pairs with Perinatal Mental Disorders.

Maternal perinatal mental disorders (PMD) are associated with developmental and behavioral problems in children, probably mediated by the programming of the hypothalamic-pituitary-adrenal (HPA) axis. Increased cortisol concentrations during the antenatal and perinatal periods have been related to long-term effects on children's behavior and stress response. We aimed to investigate the association of hair cortisol concentrations (HCC) between mothers, with (n = 16) and without PMD (n = 30), and their children, aged between 18 and 48 months. Participants were evaluated with a clinical interview and questionnaires for the Depression Anxiety Stress Scale and the Child Behavior Checklist for ages 1½-5. Maternal and child HCCs were compared between the two groups. Children of the PMD group had increased symptoms of attention deficit hyperactivity disorder. A positive linear association between maternal and child HCC was observed only in the total sample of mother-child dyads and the control group. In the PMD group, children's HCCs were significantly associated with child anxiety/depression symptoms. Aggressive behavior and oppositional/defiant problems correlated significantly with children's own HCCs, and their mother's too. These findings suggest that a chronic dysregulation of maternal and child HPA axis and their associations in the PMD dyads may underlie the linkage among prolonged maternal stress, child behavioral/emotional problems and stress responses.

Physical Health, Media Use, Stress, and Mental Health in Pregnant Women during the COVID-19 Pandemic.

Background: The COVID-19 pandemic has led to significant changes in the care of pregnant women and their fetuses. Emerging data show elevated depression and anxiety symptoms among pregnant women. Aims: The purpose of this article is to investigate the psychological and behavioral impact of the COVID-19 pandemic on pregnant women in Greece during the first national lockdown. Methods: We used a cross-sectional, anonymous survey to collect data in two fetal medicine clinics in the largest urban centers of Greece during the months of April and May 2020. The questionnaire was largely based on the CoRonavIruS Health Impact Survey (CRISIS), and assessed sociodemographic characteristics, general health and obstetric data and COVID-19-related worries and life changes. Mood symptoms, substance use and lifestyle behaviors were assessed at two time points (3 months prior to the pandemic and the 2 weeks before taking the survey), while perceived stress was measured with the perceived stress scale (PSS-14). Results: A total of 308 pregnant women (Mage = 34.72), with a mean gestation of 21.19 weeks participated in the study. Over one-third of the women found COVID-19 restrictions stressful, and their highest COVID-19-related worry was having to be isolated from their baby. Mean PSS-14 score was 21.94, suggesting moderate stress. The strongest predictors of stress were physical and mental health status before COVID-19 and having experienced a stressful life event during their pregnancy. Compared to 3 months before the pandemic, women reported higher scores on mood symptoms (p < 0.001), TV use (p = 0.01) and social media use (p = 0.031) in the last 2 weeks before taking the survey. Conclusion: Our study provides important preliminary evidence of the negative impact of the COVID-19 pandemic and the lockdown on pregnant women's well-being and functioning.