Rapid detection of fetal compromise using input length invariant deep learning on fetal heart rate signals.

Standard clinical practice to assess fetal well-being during labour utilises monitoring of the fetal heart rate (FHR) using cardiotocography. However, visual evaluation of FHR signals can result in subjective interpretations leading to inter and intra-observer disagreement. Therefore, recent studies have proposed deep-learning-based methods to interpret FHR signals and detect fetal compromise. These methods have typically focused on evaluating fixed-length FHR segments at the conclusion of labour, leaving little time for clinicians to intervene. In this study, we propose a novel FHR evaluation method using an input length invariant deep learning model (FHR-LINet) to progressively evaluate FHR as labour progresses and achieve rapid detection of fetal compromise. Using our FHR-LINet model, we obtained approximately 25% reduction in the time taken to detect fetal compromise compared to the state-of-the-art multimodal convolutional neural network while achieving 27.5%, 45.0%, 56.5% and 65.0% mean true positive rate at 5%, 10%, 15% and 20% false positive rate respectively. A diagnostic system based on our approach could potentially enable earlier intervention for fetal compromise and improve clinical outcomes.

Rodent anogenital distance recommendations.

BACKGROUND: Measurement of rat anogenital distance (AGD) dates to at least 1912. Increased interest in endocrine disrupting chemicals and the use of AGD as a biomarker for fetal androgen effects have increased the number of studies with this endpoint in recent decades. A literature review revealed different landmarks, methods of measurement, and methods to adjust for body weight differences. AGD is often reported to hundredths of millimeters and as such, deserves precision in all these aspects. This paper presents recommendations for the measurement and analysis of rodent AGD. METHODS: Literature and regulatory guidance documents that mentioned or measured rodent AGD were reviewed. Four adjustment methods were evaluated using available online data from three rat studies each with two generations of offspring. RESULTS: Tabulation of studies reveals that species/stocks and time of data collection, but more importantly anatomical landmarks and methods of measurement have produced a variety of results which are difficult to compare. Not all studies have adjusted for test article effects on body weight (and thus size). The four adjustment methods were fairly comparable. CONCLUSION: Recommendations are as follows. A microscopic method should be used to measure AGD of late rodent fetuses and early postnatal pups. The caudal edge of the genital tubercle and the cranial edge of the anus are clear and identifiable landmarks. The simplest adjustment is to divide individual AGDs by the cube root of animals' body weight. These recommendations will help ensure data consistency and accuracy, and facilitate meaningful comparisons across laboratories and chemical classes.

Investigation on ultrasound images for detection of fetal congenital heart defects.

Congenital heart defects (CHD) are one of the serious problems that arise during pregnancy. Early CHD detection reduces death rates and morbidity but is hampered by the relatively low detection rates (i.e., 60%) of current screening technology. The detection rate could be increased by supplementing ultrasound imaging with fetal ultrasound image evaluation (FUSI) using deep learning techniques. As a result, the non-invasive foetal ultrasound image has clear potential in the diagnosis of CHD and should be considered in addition to foetal echocardiography. This review paper highlights cutting-edge technologies for detecting CHD using ultrasound images, which involve pre-processing, localization, segmentation, and classification. Existing technique of preprocessing includes spatial domain filter, non-linear mean filter, transform domain filter, and denoising methods based on Convolutional Neural Network (CNN); segmentation includes thresholding-based techniques, region growing-based techniques, edge detection techniques, Artificial Neural Network (ANN) based segmentation methods, non-deep learning approaches and deep learning approaches. The paper also suggests future research directions for improving current methodologies.

Fetal brain response to maternal inflammation requires microglia.

In utero infection and maternal inflammation can adversely impact fetal brain development. Maternal systemic illness, even in the absence of direct fetal brain infection, is associated with an increased risk of neuropsychiatric disorders in affected offspring. The cell types mediating the fetal brain response to maternal inflammation are largely unknown, hindering the development of novel treatment strategies. Here, we show that microglia, the resident phagocytes of the brain, highly express receptors for relevant pathogens and cytokines throughout embryonic development. Using a rodent maternal immune activation (MIA) model in which polyinosinic:polycytidylic acid is injected into pregnant mice, we demonstrate long-lasting transcriptional changes in fetal microglia that persist into postnatal life. We find that MIA induces widespread gene expression changes in neuronal and non-neuronal cells; importantly, these responses are abolished by selective genetic deletion of microglia, indicating that microglia are required for the transcriptional response of other cortical cell types to MIA. These findings demonstrate that microglia play a crucial durable role in the fetal response to maternal inflammation, and should be explored as potential therapeutic cell targets.

Power-MF: robust fetal QRS detection from non-invasive fetal electrocardiogram recordings.

Objective.Perinatal asphyxia poses a significant risk to neonatal health, necessitating accurate fetal heart rate monitoring for effective detection and management. The current gold standard, cardiotocography, has inherent limitations, highlighting the need for alternative approaches. The emerging technology of non-invasive fetal electrocardiography shows promise as a new sensing technology for fetal cardiac activity, offering potential advancements in the detection and management of perinatal asphyxia. Although algorithms for fetal QRS detection have been developed in the past, only a few of them demonstrate accurate performance in the presence of noise and artifacts.Approach.In this work, we proposePower-MF, a new algorithm for fetal QRS detection combining power spectral density and matched filter techniques. We benchmarkPower-MFagainst three open-source algorithms on two recently published datasets (Abdominal and Direct Fetal ECG Database: ADFECG, subsets B1 Pregnancy and B2 Labour; Non-invasive Multimodal Foetal ECG-Doppler Dataset for Antenatal Cardiology Research: NInFEA).Main results.Our results show thatPower-MFoutperforms state-of-the-art algorithms on ADFECG (B1 Pregnancy: 99.5% ± 0.5% F1-score, B2 Labour: 98.0% ± 3.0% F1-score) and on NInFEA in three of six electrode configurations by being more robust against noise.Significance.Through this work, we contribute to improving the accuracy and reliability of fetal cardiac monitoring, an essential step toward early detection of perinatal asphyxia with the long-term goal of reducing costs and making prenatal care more accessible.

Adult Human, but Not Rodent, Spermatogonial Stem Cells Retain States with a Foetal-like Signature.

Spermatogenesis involves a complex process of cellular differentiation maintained by spermatogonial stem cells (SSCs). Being critical to male reproduction, it is generally assumed that spermatogenesis starts and ends in equivalent transcriptional states in related species. Based on single-cell gene expression profiling, it has been proposed that undifferentiated human spermatogonia can be subclassified into four heterogenous subtypes, termed states 0, 0A, 0B, and 1. To increase the resolution of the undifferentiated compartment and trace the origin of the spermatogenic trajectory, we re-analysed the single-cell (sc) RNA-sequencing libraries of 34 post-pubescent human testes to generate an integrated atlas of germ cell differentiation. We then used this atlas to perform comparative analyses of the putative SSC transcriptome both across human development (using 28 foetal and pre-pubertal scRNA-seq libraries) and across species (including data from sheep, pig, buffalo, rhesus and cynomolgus macaque, rat, and mouse). Alongside its detailed characterisation, we show that the transcriptional heterogeneity of the undifferentiated spermatogonial cell compartment varies not only between species but across development. Our findings associate 'state 0B' with a suppressive transcriptomic programme that, in adult humans, acts to functionally oppose proliferation and maintain cells in a ready-to-react state. Consistent with this conclusion, we show that human foetal germ cells-which are mitotically arrested-can be characterised solely as state 0B. While germ cells with a state 0B signature are also present in foetal mice (and are likely conserved at this stage throughout mammals), they are not maintained into adulthood. We conjecture that in rodents, the foetal-like state 0B differentiates at birth into the renewing SSC population, whereas in humans it is maintained as a reserve population, supporting testicular homeostasis over a longer reproductive lifespan while reducing mutagenic load. Together, these results suggest that SSCs adopt differing evolutionary strategies across species to ensure fertility and genome integrity over vastly differing life histories and reproductive timeframes.

Twist2 contributes to skin regeneration and hair follicle formation in mouse fetuses.

Unlike adult mammalian wounds, early embryonic mouse skin wounds completely regenerate and heal without scars. Analysis of the underlying molecular mechanism will provide insights into scarless wound healing. Twist2 is an important regulator of hair follicle formation and biological patterning; however, it is unclear whether it plays a role in skin or skin appendage regeneration. Here, we aimed to elucidate Twist2 expression and its role in fetal wound healing. ICR mouse fetuses were surgically wounded on embryonic day 13 (E13), E15, and E17, and Twist2 expression in tissue samples from these fetuses was evaluated via in situ hybridization, immunohistochemistry, and reverse transcription-quantitative polymerase chain reaction. Twist2 expression was upregulated in the dermis of E13 wound margins but downregulated in E15 and E17 wounds. Twist2 knockdown on E13 left visible marks at the wound site, inhibited regeneration, and resulted in defective follicle formation. Twist2-knockdown dermal fibroblasts lacked the ability to undifferentiate. Furthermore, Twist2 hetero knockout mice (Twist + /-) formed visible scars, even on E13, when all skin structures should regenerate. Thus, Twist2 expression correlated with skin texture formation and hair follicle defects in late mouse embryos. These findings may help develop a therapeutic strategy to reduce scarring and promote hair follicle regeneration.

Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth.

Mechanisms underlying human hepatocyte growth in development and regeneration are incompletely understood. In vitro, human fetal hepatocytes (FH) can be robustly grown as organoids, while adult primary human hepatocyte (PHH) organoids remain difficult to expand, suggesting different growth requirements between fetal and adult hepatocytes. Here, we characterize hepatocyte organoid outgrowth using temporal transcriptomic and phenotypic approaches. FHs initiate reciprocal transcriptional programs involving increased proliferation and repressed lipid metabolism upon initiation of organoid growth. We exploit these insights to design maturation conditions for FH organoids, resulting in acquisition of mature hepatocyte morphological traits and increased expression of functional markers. During PHH organoid outgrowth in the same culture condition as for FHs, the adult transcriptomes initially mimic the fetal transcriptomic signatures, but PHHs rapidly acquire disbalanced proliferation-lipid metabolism dynamics, resulting in steatosis and halted organoid growth. IL6 supplementation, as emerged from the fetal dataset, and simultaneous activation of the metabolic regulator FXR, prevents steatosis and promotes PHH proliferation, resulting in improved expansion of the derived organoids. Single-cell RNA sequencing analyses reveal preservation of their fetal and adult hepatocyte identities in the respective organoid cultures. Our findings uncover mitogen requirements and metabolic differences determining proliferation of hepatocytes changing from development to adulthood.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

Effect of Direct and Mediated through Maternal Organism Activation of the Catecholaminergic System on Heart Rate Parameters in Rat Fetuses.

We performed a comparative analysis of direct and mediated through the maternal organism effects of elevated catecholamine concentration on changes in the cardiac activity parameters in female rats and their fetuses on gestation days 18 and 20 under in vivo conditions. Administration of L-DOPA, a precursor of catecholaminergic transmitters, did not cause chronotropic effects in fetuses. Analysis of HR variability showed that in fetuses, irrespective of the administration route, there was an increase in nervous influences while the leading role of humoral-metabolic factors in the regulation of HR was preserved. In females receiving L-DOPA injection on day 18 of gestation, a decrease in humoral-metabolic and an increase in nerve effects were observed; in rats injected with L-DOPA on day 20 of gestation, an increase in sympathetic influences was found. Administration of L-DOPA to fetuses provoked a slight increase in the power of all components of the heart rhythm periodogram spectrum in females on day 18 of gestation and their decrease on day 20. Changes in the parameters of HR variability in females can confirm the hypothesis that in the "mother-fetus" system, the heart rhythm in the mother can be affected by both maternal and fetal influences presumably through the humoral-metabolic regulation.

PSFHS: Intrapartum ultrasound image dataset for AI-based segmentation of pubic symphysis and fetal head.

During the process of labor, the intrapartum transperineal ultrasound examination serves as a valuable tool, allowing direct observation of the relative positional relationship between the pubic symphysis and fetal head (PSFH). Accurate assessment of fetal head descent and the prediction of the most suitable mode of delivery heavily rely on this relationship. However, achieving an objective and quantitative interpretation of the ultrasound images necessitates precise PSFH segmentation (PSFHS), a task that is both time-consuming and demanding. Integrating the potential of artificial intelligence (AI) in the field of medical ultrasound image segmentation, the development and evaluation of AI-based models rely significantly on access to comprehensive and meticulously annotated datasets. Unfortunately, publicly accessible datasets tailored for PSFHS are notably scarce. Bridging this critical gap, we introduce a PSFHS dataset comprising 1358 images, meticulously annotated at the pixel level. The annotation process adhered to standardized protocols and involved collaboration among medical experts. Remarkably, this dataset stands as the most expansive and comprehensive resource for PSFHS to date.

Dendritic Cells and the Establishment of Fetomaternal Tolerance for Successful Human Pregnancy.

Pregnancy is a remarkable event where the semi-allogeneic fetus develops in the mother's uterus, despite genetic and immunological differences. The antigen handling and processing at the maternal-fetal interface during pregnancy appear to be crucial for the adaptation of the maternal immune system and for tolerance to the developing fetus and placenta. Maternal antigen-presenting cells (APCs), such as macrophages (Mφs) and dendritic cells (DCs), are present at the maternal-fetal interface throughout pregnancy and are believed to play a crucial role in this process. Despite numerous studies focusing on the significance of Mφs, there is limited knowledge regarding the contribution of DCs in fetomaternal tolerance during pregnancy, making it a relatively new and growing field of research. This review focuses on how the behavior of DCs at the maternal-fetal interface adapts to pregnancy's unique demands. Moreover, it discusses how DCs interact with other cells in the decidual leukocyte network to regulate uterine and placental homeostasis and the local maternal immune responses to the fetus. The review particularly examines the different cell lineages of DCs with specific surface markers, which have not been critically reviewed in previous publications. Additionally, it emphasizes the impact that even minor disruptions in DC functions can have on pregnancy-related complications and proposes further research into the potential therapeutic benefits of targeting DCs to manage these complications.

HSD17B1 Compensates for HSD17B3 Deficiency in Fetal Mouse Testis but Not in Adults.

Hydroxysteroid (17ß) dehydrogenase (HSD17B) enzymes convert 17-ketosteroids to 17beta-hydroxysteroids, an essential step in testosterone biosynthesis. Human XY individuals with inactivating HSD17B3 mutations are born with female-appearing external genitalia due to testosterone deficiency. However, at puberty their testosterone production reactivates, indicating HSD17B3-independent testosterone synthesis. We have recently shown that Hsd17b3 knockout (3-KO) male mice display a similar endocrine imbalance, with high serum androstenedione and testosterone in adulthood, but milder undermasculinization than humans. Here, we studied whether HSD17B1 is responsible for the remaining HSD17B activity in the 3-KO male mice by generating a Ser134Ala point mutation that disrupted the enzymatic activity of HSD17B1 (1-KO) followed by breeding Hsd17b1/Hsd17b3 double-KO (DKO) mice. In contrast to 3-KO, inactivation of both HSD17B3 and HSD17B1 in mice results in a dramatic drop in testosterone synthesis during the fetal period. This resulted in a female-like anogenital distance at birth, and adult DKO males displayed more severe undermasculinization than 3-KO, including more strongly reduced weight of seminal vesicles, levator ani, epididymis, and testis. However, qualitatively normal spermatogenesis was detected in adult DKO males. Furthermore, similar to 3-KO mice, high serum testosterone was still detected in adult DKO mice, accompanied by upregulation of various steroidogenic enzymes. The data show that HSD17B1 compensates for HSD17B3 deficiency in fetal mouse testis but is not the enzyme responsible for testosterone synthesis in adult mice with inactivated HSD17B3. Therefore, other enzymes are able to convert androstenedione to testosterone in the adult mouse testis and presumably also in the human testis.

Fetal magnetocardiographic recordings with a prototype bed-based array system of optically-pumped magnetometers.

OBJECTIVE: To record and extract features of fetal cardiac activities with a semi-rigid prototype optically-pumped magnetometers (OPM) sensor array. METHODS: Fetal magnetocardiography (fMCG) data were collected from 15 pregnant women between 28 and 40 weeks gestation. Mothers were lying flat in a customized bed with sensors touching their abdomen from below using a prototype grid. fMCG was extracted to perform standard fetal heart rate variability (FHRV) analysis. RESULTS: fMCG was observed in 13 of the 15 pregnant women. OPM FHRV indicators were in the range of previous SQUID studies. CONCLUSION: Semi-rigid prototype OPM system has the ability to record quality fMCG. fMCG is capable of identifying lethal cardiac rhythm disturbances in the fetus. Our novel application of OPM technology may lower costs and increase maternal comfort, thus expanding fMCG's generalizability.

Human Umbilical Cord Mesenchymal Stromal Cell-Derived Extracellular Vesicles Induce Fetal Wound Healing Features Revealed by Single-Cell RNA Sequencing.

The potential of human umbilical cord mesenchymal stromal cell-derived extracellular vesicles (hucMSC-EVs) in wound healing is promising, yet a comprehensive understanding of how fibroblasts and keratinocytes respond to this treatment remains limited. This study utilizes single-cell RNA sequencing (scRNA-seq) to investigate the impact of hucMSC-EVs on the cutaneous wound microenvironment in mice. Through rigorous single-cell analyses, we unveil the emergence of hucMSC-EV-induced hematopoietic fibroblasts and MMP13+ fibroblasts. Notably, MMP13+ fibroblasts exhibit fetal-like expressions of MMP13, MMP9, and HAS1, accompanied by heightened migrasome activity. Activation of MMP13+ fibroblasts is orchestrated by a distinctive PIEZO1-calcium-HIF1α-VEGF-MMP13 pathway, validated through murine models and dermal fibroblast assays. Organotypic culture assays further affirm that these activated fibroblasts induce keratinocyte migration via MMP13-LRP1 interactions. This study significantly contributes to our understanding of fibroblast heterogeneities as well as intercellular interactions in wound healing and identifies hucMSC-EV-induced hematopoietic fibroblasts as potential targets for reprogramming. The therapeutic targets presented by these fibroblasts offer exciting prospects for advancing wound healing strategies.

The profile of steroid hormones in human fetal and adult ovaries.

BACKGROUND: Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. METHODS: We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. RESULTS: Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17ß-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures. CONCLUSIONS: Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.

Evaluating pregnancy termination decisions for fetal anomalies: a retrospective study in a tertiary referral center.

OBJECTIVE: The aim of this study was to examine the factors that influence pregnancy termination due to fetal anomalies, regardless of gestational age, within the legal framework of Turkey. METHODS: This retrospective study was conducted between January 2021 and July 2023 at a tertiary perinatology center to analyze patients undergoing pregnancy termination. The process involved multidisciplinary evaluations and informed consent, resulting in 326 pregnancy terminations, categorized by gestational timing. RESULTS: Of the 326 patients studied, 219 opted for terminations. Gestational week at diagnosis significantly influenced the decision to terminate, with fetal anomalies being the primary indication. Chromosomal abnormalities accounted for 15.9% of the cases, while structural anomalies and maternal disorders accounted for 84.1% and structural malformations accounted for 84.1% of the cases. Late terminations (≥23 weeks) accounted for 30% of cases and required complex procedures. CONCLUSION: The findings of this study indicate that maternal demographic factors have a limited impact on termination decisions. Early diagnosis of fetal anomalies is crucial for informed decision-making and emotional support, and the psychological consequences of late termination highlight the need for maternal support. Obstetricians play a vital role in facilitating early intervention. This study underscores the complex medical, ethical, and psychological aspects of pregnancy termination due to fetal anomalies. It emphasizes the importance of a holistic approach, considering medical, ethical, and psychological factors and the crucial role of healthcare professionals in supporting families during this challenging process.

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.