Fetal Disorders Research Articles

Pathologic findings of the placenta and clinical implications - recommendations for placental examination.

The placenta is a unique and complex organ that combines the circulatory systems of two or more individuals within a single dynamic organ with a set, short lifespan. A diverse spectrum of disorders, including infections as well as metabolic, genetic, circulatory, and maturation defects, may affect its function. Pathology investigation of the placenta is key for identifying several pathogenic processes in both the mother and the foetus. Aberrant placentation, maternal and foetal vascular compromise, infection, inflammatory immunologic conditions, and disorders of maturation are elements of newly proposed classification schemes. The clinical impact of placental examination consists of diagnosing maternal and foetal disease, identifying the potential for recurrence, correlating clinical pathological findings with distinct morphologic features, and identifying the aetiology responsible for growth restriction or foetal death. Gestational trophoblastic disease occurs more frequently in the first trimester; however, in very rare cases, it can affect the term or third-trimester placenta. The application of reproducible nomenclature is expected to facilitate progress in the diagnosis and treatment of obstetric and foetal disorders with placental manifestation. Therefore, this review aims to facilitate communication between obstetricians, neonatologists, and pathologists involved in this diagnostic process.

Expert consensus on the clinical application strategy of NIPT2.0, a new-generation non-invasive prenatal screening technology

The new-generation non-invasive prenatal screening technology (NIPT2.0) is a new method successfully realized in recent years based on high-throughput sequencing to synchronously and accurately detect fetal chromosomal aneuploidies, microdeletion/microduplication syndromes and dominantly inherited monogenic disorders. NIPT2.0 can circumvent the shortcomings of previous non-invasive prenatal screening techniques (NIPT and NIPT Plus) including incapability to detect fetal monogenic disorders, insufficient accuracy of detection and low positive predictive values for certain chromosomal abnormalities (in particular trisomy 13, sex chromosomal abnormalities, and small-segment microdeletions and microduplication syndromes). How to apply NIPT2.0 reasonably and normatively to maximize its clinical value has become an issue which requires clarification. The Reproductive Health Branch of the Chinese Maternal and Child Health Care Association and the Genetic Diagnosis Branch of the Genetics Society of China have organized experts to fully discuss and jointly drafted this consensus, which has put forwards suggestions over the clinical application strategy for NIPT2.0, including the scope of application, target disease, pre-test consultation, clinical application pathway, post-test genetic counseling and intervention, quality control and limitations, for the reference by peers, with a view to standardize its application and provide better clinical service.

Identification of a novel intronic variant in COL4A2 gene associated with fetal severe cerebral encephalomalacia and subdural hemorrhage

BackgroundGenetic variants in COL4A2 are less common than those of COL4A1 and their fetal clinical phenotype has not been well described to date. We present a fetus from China with an intronic variant in COL4A2 associated with a prenatal diagnosis of severe cerebral encephalomalacia and subdural hemorrhage.MethodsWhole exome sequencing (WES) was applied to screen potential genetic causes. Bioinformatic analysis was performed to predict the pathogenicity of the variant. In in vitro experiment, the minigene assays were performed to assess the variant’s effect.ResultsIn this proband, we observed ventriculomegaly, subdural hemorrhage, and extensive encephalomalacia that initially suggested cerebral hypoxic-ischemic and/or hemorrhagic lesions. WES identified a de novo heterozygous variant c.549 + 5G > A in COL4A2 gene. This novel variant leads to the skipping of exon 8, which induces the loss of 24 native amino acids, resulting in a shortened COL4A2 protein (p.Pro161_Gly184del).ConclusionOur study demonstrated that c.549 + 5G > A in COL4A2 gene is a disease-causing variant by aberrant splicing. This finding enriches the variant spectrum of COL4A2 gene, which not only improves the understanding of the fetal neurological disorders associated with hypoxic-ischemic and hemorrhagic lesions from a clinical perspective but also provides guidance on genetic diagnosis and counseling.

Induction of Labour: What to Consider

Induction of Labour (IOL) is a method of artificially providing stimulus to the uterus to start the process of labour.1 It utilises iatrogenic therapies such as a synthetic oxytocin, cervical ripening medications, in conjunction with the artificial rupture of membranes, to imitate the physiology of labour and childbirth.2 The indication for IOL is dependent on the clinical need to optimise maternal, fetal and neonatal outcomes, juxtaposed with the potential adverse effects of the IOL process. Indications include uterine, placental and fetal growth disorders, hypertensive conditions and diabetes.3 For example, the National Institute for Clinical Excellence (NICE) recommend IOL between 37 and 38 plus six weeks for pregnant populations who have type 1 or type 2 diabetes, to prevent stillbirth and associated complications.4 The absolute effectiveness of IOL intervention in preserving maternal and fetal health is evident5 however, the World Health Organization (WHO) endorses the consideration of choice of IOL method.6

Semen Strychni Pulveratum and vomicine alleviate neuroinflammation in amyotrophic lateral sclerosis through cGAS-STING-TBK1 pathway

Ethnopharmacological relevanceAmyotrophic lateral sclerosis (ALS) is a fetal neuromuscular disorder characterized by the gradual deterioration of motor neurons. Semen Strychni pulveratum (SSP), a processed version of Semen Strychni (SS) powder, is widely used to treat ALS in China. Vomicine is one of the most primary components of SS. However, their pharmacological effects and mechanisms for ALS remain elusive. Aim of the studyThis study aimed to evaluate the neuroprotective and anti-neuroinflammatory effects of SSP and vomicine, as well as to explore their protective roles in ALS and the underlying mechanisms. Materials and methodsIn vivo, 8-week-old hSOD1-WT mice and hSOD1-G93A mice were orally administered different concentrations of SSP (SSP-L = 5.46 mg/ml, SSP-M = 10.92 mg/ml or SSP-H = 16.38 mg/ml) once every other day for 8 weeks. A series of experiments, including body weight measurement, footprint tests, Hematoxylin & Eosin staining, and Nissl staining, were performed to evaluate the preventive effect of SSP. Immunofluorescence staining, western blotting, and RT-qPCR were subsequently performed to evaluate activation of the cGAS-STING-TBK1 pathway in the spinal cord. In vitro, hSOD1G93A NSC-34 cells were treated with vomicine to further explore the pharmacological mechanism of vomicine in the treatment of ALS via the cGAS-STING-TBK1 pathway. ResultsSSP improved motor function, body weight loss, gastrocnemius muscle atrophy, and motor neuron loss in the spine and cortex of hSOD1-G93A mice. Furthermore, the cGAS-STING-TBK1 pathway was activated in the spinal cord of hSOD1-G93A mice, with activation predominantly observed in neurons and microglia. However, the levels of cGAS, STING, and pTBK1 proteins and cGAS, IRF3, IL-6, and IL-1β mRNA were reversed following intervention with SSP. Vomicine not only downregulated the levels of cGAS, TBK1, IL-6 and IFN-β mRNA, but also the levels of cGAS and STING protein in hSOD1G93A NSC-34 cells. ConclusionThis study demonstrated that SSP and vomicine exert neuroprotective and anti-neuroinflammatory effects in the treatment of ALS. SSP and vomicine may reduce neuroinflammation by regulating the cGAS-STING-TBK1 pathway, and could thereby play a role in ALS treatment.

Prenatal Manifestation of Transient Abnormal Myelopoiesis: Case Report and Review of the Literature.

Background: Congenital malignancies are unusual fetal conditions, and therefore, the data on their prenatal manifestation are limited. Transient abnormal myelopoiesis (TAM) is a hematologic disorder characteristic for babies with trisomy 21 and based on the transient appearance of blast cells in peripheral blood. Methods: This paper presents prenatal manifestation of congenital TAM in a newborn with normal karyotype and reviews the literature on prenatal manifestation of this disorder. Results: A pregnant woman in her third pregnancy referred herself to the hospital for reduced fetal movements at 30 weeks of gestation. Admission's ultrasound scan showed an increased middle cerebral artery peak systolic velocity together with hepatomegaly. The patient was admitted to the labor ward for cardiotocography monitoring which showed acute fetal distress with repeated unprovoked decelerations. An emergency cesarean section was conducted and a phenotypically normal female newborn with low Apgar score was delivered. Further examination of the peripheral blood revealed anemia and leukocytosis with high blast proportion. A bone marrow aspirate revealed 70.2% of blasts in a sample with an abnormal karyotype of 47 XX+21. Cytogenetic analysis of the blasts with later microarray comparative genomic hybridization confirmed the presence of GATA1 mutation. However, the buccal smear showed a normal karyotype in the infant. The disease was classified as TAM. Conclusions: Our study demonstrates a rare case of prenatal manifestation of TAM in a neonate with a normal karyotype. Obstetricians should pay attention to symptoms like high MCA PSV and hepatosplenomegaly as possible causes of fetal hematological disorders and differentiate it with infection or isoimmunization.

Zika virus vertical transmission induces neuroinflammation and synapse impairment in brain cells derived from children born with Congenital Zika Syndrome

Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.

Trimester-specific association between fetal growth and physical activity in pregnant women: total physical activity vs moderate-to-vigorous exercise.

To investigate the trimester-specific associations between maternal total physical activity level vs moderate-to-vigorous exercise and fetal growth disorders. We analyzed 2062 mother-neonate pairs participating in the longitudinal China Medical University Birth Cohort Study. The Pregnancy Physical Activity Questionnaire was used to assess the physical activity level of women during the three trimesters. A higher level of total physical activity was defined as meeting or exceeding the cohort-specific 75th percentile, and a higher level of exercise was defined according to the Physical Activity Guidelines for Americans. Fetal growth disorder was defined as small-for-gestational age (SGA) or large-for-gestational age (LGA) at birth. Of the neonates included in this study, 7.1% were SGA and 15.5% were LGA. A higher level of total physical activity during the first trimester (adjusted relative risk (aRR), 0.62 (95% CI, 0.42-0.91)) and second trimester (aRR, 0.62 (95% CI, 0.41-0.95)) was associated with a lower risk of SGA, and a higher level of total physical activity during the third trimester was associated with a lower risk of LGA (aRR, 0.73 (95% CI, 0.54-0.97)). When analyzing physical activity by subtype, a higher level of occupational physical activity during the first and second trimesters was associated negatively with SGA risk, and higher levels of occupational and low-intensity physical activity during the first trimester were associated negatively with LGA risk. No significant association was found between maternal adherence to the Physical Activity Guidelines for Americans and risk of fetal growth disorders. A higher total physical activity level during the first and second trimesters was associated with a decreased risk of SGA, whereas a higher total physical activity level in the third trimester was associated with a decreased risk of LGA. Pregnant women should be advised to increase their total physical activity levels instead of focusing on engaging in only moderate-to-vigorous exercise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Continuous Glucose Monitoring-Derived Differences in Pregnancies With and Without Adverse Perinatal Outcomes.

To evaluate whether continuous glucose monitoring (CGM)-derived glycemic patterns observed throughout pregnancy were associated with adverse perinatal outcomes, specifically fetal growth disorders and hypertensive disorders of pregnancy (HDP). We conducted a prospective observational study of individuals with viable singleton pregnancies and screening hemoglobin A 1c levels less than 6.5%. Those with preexisting diabetes were excluded. Enrollment occurred at the earliest gestational age before 17 weeks. Participants wore blinded continuous glucose monitors consecutively as willing until delivery. Those with at least 14 days of CGM data were included in analysis. Rates of large-for-gestational-age (LGA) neonates, small-for-gestational age (SGA) neonates, and HDP were assessed. Continuous glucose monitoring-derived glycemic metrics were calculated, including mean glucose level and percent time above and below thresholds. Two-sample t tests were used to compare glycemic metrics between participants with and without adverse perinatal outcomes. Of 937 participants enrolled, 760 met inclusion criteria. Those delivering LGA neonates or who were diagnosed with HDP had higher mean glucose levels (102±9 vs 100±8, P =.01 and 103±8 vs 99±8, P <.001) and spent more time above 120 mg/dL (median 16% vs 12%, P =.006, and 16% vs 12%, P <.001, respectively) and above 140 mg/dL (median 3.9% vs 2.8%, P =.006, and 3.5% vs 2.8%, P <.001, respectively) throughout gestation than those without these outcomes. These findings were present regardless of gestational diabetes mellitus status. Participants with SGA neonates had lower mean glucose levels (97±7 vs 101±8, P =.01) and spent less time above 140 mg/dL (median 1.6% vs 2.3%, P =.01) and more time below 63 mg/dL (median 3.0% vs 2.3%, P =.02) than those without SGA neonates. Individuals with LGA neonates or HDP exhibit a slightly higher mean glucose levels and spend more time hyperglycemic in early pregnancy than those who do not experience these outcomes.

Prediction of Fetal Health Status Using Machine Learning

The goal of this promising area of study is to enhance prenatal care and lower fetal morbidity and mortality by utilizingmachine learning to anticipate fetal disease. In this study, we present a machine learning-based strategy for predicting fetaldiseases from clinical data. First, we gathered a sizable collection of clinical information from expectant mothers with various fetal disorders. Using clinical guidelines, we pre-processed the data and retrieved pertinent features. We integrated a range of machine learning algorithms, including logistic regression, support vector machines, decision trees, and random forests, to train and test our model. We evaluated the performance of our model using severalfactors, such as accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC-ROC).The results of this study demonstrate how machine learning algorithms can accurately forecast fetal health status. The developed models achieve good accuracy and AUC-ROC ratings todistinguish between healthy and at-risk fetuses. The interpretability study identifies key clinical characteristics that have a significant impact on the prediction, providing medical practitioners with useful information when making decisions about prenatal care. Through the provision of more unbiasedand precise assessments of fetal health status, machine learning techniques incorporated into prenatal care have the potential to transform the industry. By providing accurate and early projections, this technology can assist healthcare professionals in identifying high-risk pregnancies and carrying out the necessary procedures, improving mother and fetal outcomes. Future research should concentrate on verifying and improving predictive models on larger and more varied datasets to ensure real-world applicability and reliability

Foetal growth restriction and maternal hypertensive disorders: a case series from Udine

Foetal growth restriction and maternal hypertensive disorders: a case series from Udine

Comprehensive Circulating DNA Profiling in Maternal Plasma Enabled the Identification of a Molecular Signature for the Detection of Fetal Growth Disorders at the First Pregnancy Trimester

Background: Early diagnosis, close follow-up and timely delivery constitute the main elements for the appropriate detection and management of pregnancies with fetal growth disorders (FGD). Besides the unprecedented technological development in screening of fetal growth abnormalities based on fetal biometry by ultrasound, inaccuracies still hinder FGD detection and assessment especially at early stage. Hence, there is an unmet need for reliable prenatal biomarkers of fetal growth, which can be assessed using low-invasive approaches. We hypothesize that the dysregulation of epigenetic mechanisms underly the etiology of FGD in infants impacting the shedding of genetic material into maternal blood. As a corollary, we propose that markers in circulating fetal DNA (cfDNA) in maternal blood can be used as early detection markers of FGDs. Methods: 56 pregnant women were recruited in this study. Maternal blood sample was prospectively collected from each subject at first trimester and plasma circulating DNA (cirDNA) was isolated. The number of Small, Large and Adequate for Gestational Age (SGA n=11, LGA n=18, and AGA n=27, respectively) were determined at birth according to weight and gestational age. The total amount of plasma cirDNA in each subject was quantified using qPCR. cirDNA fragmentation was assessed using specific qPCR assays corresponding to intact, nucleosome-size, and fragmented DNA, respectively. The mitochondrial/nuclear cirDNA was calculated using specific qPCR assays. cirDNA methylation profiles were studied in 10 genes associated with placental homeostasis. Furthermore, machine learning approaches were applied to build a molecular signature for the prediction of LGA and SGA occurrence using first trimester samples. Prediction accuracy was assessed by Receiving-Operating Curve (ROC) analysis and Positive and Negative Predictive values (PPV and NPV, respectively) were calculated. Results: We observed an increase in the total concentration of plasma cirDNA in SGA (mean cirDNA=9.40 ± 5.49 ng/mL) and LGA (mean cirDNA=12.36 ± 4.24 ng/mL) compared to AGA pregnancies (mean cirDNA=8.48 ± 3.16 ng/mL), although the differences were not statistically significant (p=0283; Kruskal Wallis test). The fraction of fragmented DNA was significantly increased (p=0.002) in SGA (mean DNA fragmentation index, DFI=2.38 ± 0.14), and SGA (mean DFI=2.47± 0.25) compared with AGA pregnancies (mean DFI=1.56 ± 0.15). Likewise, the ratio of mitochondrial/nuclear DNA was significantly increased (p=0.005) in LGA (mean FC=0.78 ± 0.31) and LGA (mean FC=1.20 ± 0.32 compared with AGA pregnancies (mean FC=0.23 ± 0.05). DNA methylation profiles also shown distinctive patterns. Out of the 10 selected loci, we detected 4 genes showing significant differential methylation differences (p&lt;0.05) across the SGA, LGA and SGA samples at first trimester. Using a machine learning approach, we combined these molecular and epigenetic cirDNA markers in a single signature which discriminates between FGD and AGA pregnancies with high accuracy (AUC=0.93) In addition, the performance of the signature was further evaluated according to positive predictive and negative predictive values (PPV and NPV, respectively), achieving 93% PPV and 82% NPV. Conclusions: Our findings demonstrate that cirDNA epigenetic variables in maternal blood cirDNA can serve as FGD markers. Our novel marker panels will enable accurate prediction of FGDs using a low invasive approach that can be implemented as early as the first gestational trimester. The application of these panels in a clinical setting holds the potential to enable a disruptive path toward precision medicine in FGD.

Risks of adverse obstetric outcomes among female survivors of adolescent and young adult cancer in England (TYACSS): a population-based, retrospective cohort study

There are limited data on the risks of obstetric complications among survivors of adolescent and young adult cancer with most previous studies only reporting risks for all types of cancers combined. The aim of this study was to quantify deficits in birth rates and risks of obstetric complications for female survivors of 17 specific types of adolescent and young adult cancer. The Teenage and Young Adult Cancer Survivor Study (TYACSS)-a retrospective, population-based cohort of 200 945 5-year survivors of cancer diagnosed at age 15-39 years from England and Wales-was linked to the English Hospital Episode Statistics (HES) database from April 1, 1997, to March 31, 2022. The cohort included 17 different types of adolescent and young adult cancers. We ascertained 27 specific obstetric complications through HES among 96 947 women in the TYACSS cohort. Observed and expected numbers for births and obstetric complications were compared between the study cohort and the general population of England to identify survivors of adolescent and young adult cancer at a heighted risk of birth deficits and obstetric complications relative to the general population. Between April 1, 1997, and March 31, 2022, 21 437 births were observed among 13 886 female survivors of adolescent and young adult cancer from England, which was lower than expected (observed-to-expected ratio: 0·68, 95% CI 0·67-0·69). Other survivors of genitourinary, cervical, and breast cancer had under 50% of expected births. Focusing on more common (observed ≥100) obstetric complications that were at least moderately in excess (observed-to-expected ratio ≥1·25), survivors of cervical cancer were at risk of malpresentation of fetus, obstructed labour, amniotic fluid and membranes disorders, premature rupture of membranes, preterm birth, placental disorders including placenta praevia, and antepartum haemorrhage. Survivors of leukaemia were at risk of preterm delivery, obstructed labour, postpartum haemorrhage, and retained placenta. Survivors of all other specific cancers had no more than two obstetric complications that exceeded an observed-to-expected ratio of 1·25 or greater. Survivors of cervical cancer and leukaemia are at risk of several serious obstetric complications; therefore, any pregnancy should be considered high-risk and would benefit from obstetrician-led antenatal care. Despite observing deficits in birth rates across all 17 different types of adolescent and young adult cancer, we provide reassurance for almost all survivors of adolescent and young adult cancer concerning their risk of almost all obstetric complications. Our results provide evidence for the development of clinical guidelines relating to counselling and surveillance of obstetrical risk for female survivors of adolescent and young adult cancer. Children with Cancer UK, The Brain Tumour Charity, and Academy of Medical Sciences.

Quantifying alcohol's harm to others: a research and policy proposal.

Just under 2.5million people die annually due to alcohol use. This global estimate, however, excludes most of the health burden borne by others than the alcohol user. Alcohol's harm to others includes a multitude of conditions, such as trauma from traffic crashes, fetal disorders due to prenatal exposure to alcohol, as well as interpersonal and intimate partner violence. While alcohol's causal role in these conditions is well-established, alcohol's harm to others' contribution to the overall health burden of alcohol remains unknown. This knowledge gap leads to a situation in which alcohol policy and prevention strategies largely focus on the reduction of alcohol's detrimental health harms on the alcohol users, neglecting affected others and population groups most vulnerable to these harms, including women and children. In this article, we seek to elucidate why estimates for alcohol's harm to others are lacking and offer guidance for future research. We also argue that a full assessment of the alcohol health burden that includes the harm caused by others' alcohol use would enhance the visibility and public awareness of such harms, and advancing the evaluation of policy interventions to mitigate them.

Automatic cortical surface parcellation in the fetal brain using attention-gated spherical U-net.

Cortical surface parcellation for fetal brains is essential for the understanding of neurodevelopmental trajectories during gestations with regional analyses of brain structures and functions. This study proposes the attention-gated spherical U-net, a novel deep-learning model designed for automatic cortical surface parcellation of the fetal brain. We trained and validated the model using MRIs from 55 typically developing fetuses [gestational weeks: 32.9 ± 3.3 (mean ± SD), 27.4-38.7]. The proposed model was compared with the surface registration-based method, SPHARM-net, and the original spherical U-net. Our model demonstrated significantly higher accuracy in parcellation performance compared to previous methods, achieving an overall Dice coefficient of 0.899 ± 0.020. It also showed the lowest error in terms of the median boundary distance, 2.47 ± 1.322 (mm), and mean absolute percent error in surface area measurement, 10.40 ± 2.64 (%). In this study, we showed the efficacy of the attention gates in capturing the subtle but important information in fetal cortical surface parcellation. Our precise automatic parcellation model could increase sensitivity in detecting regional cortical anomalies and lead to the potential for early detection of neurodevelopmental disorders in fetuses.

Exposure to Mercury in the Air and Its Effect on Cardiovascular Diseases (CVD): A Systematic Review.

We aimed to verify the exposure to mercury in the air and its effect on cardiovascular disorders. The review was conducted using PubMed, Scopus, Web of Science, Embase, and national databases (such as SID) from 1995-2022. Mercury exposure can cause many disorders in humans, including neurodevelopmental disorders in fetuses and children, adverse cardiovascular outcomes, hypertension, and diabetes. Mercury is a human neurotoxin, and in recent years its potentially harmful effects on cardiovascular disease (CVD) have raised concerns, mainly due to mercury's role in reducing oxidative stress. Possible mechanisms of mercury toxicity in CVD include mercury-selenium interaction, increased lipid peroxidation, and oxidative stress. In this article, we review studies that have investigated the relationship between mercury and CVD.

Increased risk of fetal left–right asymmetry disorders associated with maternal SARS-CoV-2 infection during the first trimester

Our center has observed a substantial increase in the detection rate of fetal left–right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case–control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t-test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case–control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P = .026) and infection during the first trimester (96.55% vs 3.45%, P = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.

Use of Sotrovimab in Pregnancy: Experiences from the COVID-19 International Drug Pregnancy Registry.

Available data regarding the safety and efficacy of sotrovimab in pregnant patients remain limited due to their exclusion from clinical trials. The COVID-19 International Drug Pregnancy Registry (COVID-PR) was established to gather comprehensive safety data from pregnant women who have received monoclonal antibody (mAb) or antiviral treatments for mild, moderate, or severe coronavirus disease 2019 (COVID-19) during pregnancy. Participants actively contributed self-reported data concerning their COVID-19 symptoms, in addition to sociodemographic and health-related characteristics. Obstetric, neonatal, and infant outcomes were also documented, with follow-up extending up to 12 months after childbirth. As of 30 November 2023, sotrovimab was administered to 39 participants enrolled in the COVID-PR. At the time of this report, 26 participants had given birth, with nine deliveries performed via cesarean section. The infants' birthweight ranged from 2381g to 4762g, with a mean of 3439.91g. Twenty-five infants were born at ≥37weeks. A total of 31 adverse events (AEs) were reported by 12 participants. The most frequently reported AE was gestational hypertension, observed in three participants. COVID-19 re-infection, fatigue, gestational diabetes, headache, and morning sickness were each reported by two participants. Of the reported AEs, eight (in five participants) were classified as serious, including four AEs (prolonged labor, pre-eclampsia, polyhydramnios, premature labor) that affected pregnancy. Seven of these eight serious AEs (SAEs) were found to be unrelated to sotrovimab, with one event (urinary retention) not assessable. A total of 44 AEs were reported in 19 delivered infants or in utero fetuses. The most common were COVID-19 (n=6 events), ear infection (n=5 events), neonatal dyspnea (n=3 events), and respiratory syncytial virus infection (n=3 events). Sixteen AEs (in 11 infants/fetuses) were classified as serious, including one report each of fetal cardiac disorder, congenital ankyloglossia, persistent right umbilical vein, and congenital hydronephrosis; the latter was considered a major congenital malformation. For all assessable SAEs, causality of sotrovimab treatment was ruled out based on lack of a temporal relationship alone or in combination with absence of a plausible mechanism. A sizable proportion of sotrovimab-treated participants in the COVID-PR had underlying medical conditions associated with an increased risk of severe COVID-19. None of the assessable SAEs were considered to be related to sotrovimab treatment.

Neonatal complications in pregnant women due to alcohol and tobacco addiction

Introduction: alcohol and tobacco, present in society for centuries, represent serious risks during pregnancy. Alcohol can cause serious fetal disorders, such as FASD, while tobacco is linked to low birth weight and breathing problems. Both increase the probability of premature birth and neonatal complications, requiring preventive actions and urgent treatment. Objective: to determine neonatal complications in pregnant women with alcohol and tobacco addiction. Methodology: it is a literature review of the literature between 2019 and 2024. Academic databases such as Sciencie Direct, Google Scholar, SciELO, PubMed and Boolean operators were used to broaden the search. The PRISMA method is used to assess the quality of the studies. Results: the initial information search revealed a total set of 1532 articles, of which 60 met the eligibility criteria. Of these, 46 were not relevant, leaving a total of 15 records that contributed to the fulfillment of the study objectives and were used to carry out the meta-analysis. Conclusion: the consumption of alcohol and tobacco during pregnancy causes several neonatal complications, among them we can mention premature birth, low birth weight, among others

Case Report: Dichorionic-Diamniotic Twin Pregnancy Complicated by a Migrational Anomaly Mimicking a Brain Neoplasm

Background Fetal brain anomalies have a wide differential diagnosis including: (1) congenital genetic and vascular disorders; (2) acquired causes such as infection and hypoxic-ischemic injury; and rarely (3) neoplasm. Fetal brain anomalies are also infrequently seen. Consequently, there is limited literature describing methods of distinguishing these conditions, barring the presence of the most characteristic findings on imaging. Objective The purpose of this report is to describe the critical parts of our workup that helped us distinguish a fetal brain migrational disorder from a neoplasm. Study Design Case report of a single patient seen at Tripler Army Medical Center and Children’s Hospital of Los Angeles Case Summary (Results) 24-year-old gravida 1 with a dichorionic-diamniotic twin pregnancy was found to have an intracranial abnormality in Twin A on a transabdominal ultrasound performed at 16w1d gestation. Serial prenatal ultrasounds and complementary fetal magnetic resonance imaging (MRI) studies were performed to distinguish a possible fetal brain tumor from a migrational disorder. Fetal MRIs performed at 19w1d and 23w0d demonstrated a mass-like region increasing in size which was interpreted as highly suggestive of an enlarging fetal brain tumor. Ultimately, additional radiologic findings of fluid filled clefts and polymicrogyria visualized at 32 weeks led to a definitive diagnosis of a fetal migrational disorder. Conclusion Features used to diagnose fetal brain anomalies are often nonspecific and develop throughout a gestation. Most of these diagnoses require multiple imaging studies carried out over time to identify key features, and characteristic key features often do not present until very late in a gestation. The differential diagnosis of a dysplastic appearing mass-like region growing in size throughout a pregnancy should include fetal migrational disorders.