Coronavirus disease 2019 (COVID-19) is a global respiratory infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The Omicron variant has become the dominant strain in the global pandemic, exhibiting significantly lower pathogenicity compared to earlier variants. Although the number of infections remains high, the illness caused by the Omicron variant is gradually transitioning into a common respiratory infectious disease. As the pandemic continues to spread, the potential risks to fetal growth and development, pregnancy outcomes, and vertical transmission of novel coronavirus during pregnancy have become major societal concerns. Although reports of poor maternal placental perfusion in the third-trimester of pregnancy have been documented since the onset of the COVID-19 pandemic, data on maternal placental perfusion and pregnancy outcomes during the first-trimester remain limited [1, 2].

Placenta is a crucial organ for the exchange of nutrients between the mother and the fetus, and its function directly affects fetal outcomes. During normal pregnancy, the uterine artery (UtA), a branch of the internal iliac artery, transforms from a high-resistance vessel to low-resistance vessel, forming spiral arteries. These arteries undergo trophoblast infiltration and remodelling, where vascular endothelial cells are replaced by trophoblast cells, and vascular smooth muscle is replaced by fibrin, widening the lumen to meet the demands of pregnancy and ensure adequate blood supply to the fetus [3]. Studies have reporter a significant increase in the levels of angiotensin-converting enzyme 2 (ACE2) receptors in the uterus and placenta during pregnancy following SARS-CoV-2 infection [4, 5]. The interaction between SARS-CoV-2 and endothelial cells can lead to microthrombosis, suggesting a potential link between infection and impaired placental function. In this study, Microvascular-flow (MV-Flow) technology was utilized to measure the placental vascular index, referred to as VI^MV, in both the first-trimester infection group and normal pregnancy group. Additionally, Doppler ultrasound technology was used to measure the maximum systolic/diastolic (S/D) blood flow velocity, resistance index (RI), and pulsatile index (PI) of the bilateral UtA in pregnant women. The differences between the two groups of pregnant women and their fetuses were compared. Furthermore, the pregnancy outcome of the fetus in the infected group was observed in order to provide more accurate ultrasound quantitative indicators for clinical practice and to establish a theoretical basis for future diagnosis and treatment.

A total of 37 women with singleton pregnancies were included in this study, comprising 7 in the normal group and 30 in the infection group. No significant differences were observed in age, gestational weeks, number of pregnancies production times, placental position, or placental thickness between the two groups (Table 1).

No significant differences in VI^MV were observed between the two groups when using ellipse, rectangular, and manual tracing methods to detect the center of the placenta (Table 2 and Fig. 1). Compared to the ultrasound parameters of the two groups, the VI^MV value in the infection group were greater than that in the control group. Except for PI of the right UtA, the S/D, PI, and RI of UtA were not statistically significant between the two groups (p $>$ 0.05) (Table 3).

Fig. 1.

MV-Flow showing placental microvasculature. (A–C) Infection group: rectangle, ellipse, and manual trace ratios were 61.0%, 60.5%, and 71.6%, respectively. (D–F) Normal group: rectangle,ellipse,and manual trace ratios were 77.9%, 85.1%, and 78.2%. ROI, region of interest. MV-Flow, Microvascular-flow.

In the infection group, there were 12 cases with good pregnancy outcomes and 4 cases with adverse pregnancy outcomes. There were no statistically significant differences in VI^MV values, placental thickness, S/D, PI, RI of the UtA, and neonatal values between the favorable pregnancy group and the adverse pregnancy group (Table 4).

Early pregnancy infection with COVID-19 during the Omicron pandemic did not significantly affect placental perfusion in pregnant women, nor were there significant differences in adverse pregnancy outcomes between women with early infection and those who were uninfected. These findings indicate that early Omicron infection does not significantly affect the growth and development of both placenta and fetus, nor does it increases the risk of adverse pregnancy outcomes.

During the first-trimester of pregnancy, the S/D value of the UtA, a branch of the internal iliac artery, is commonly used as an indicator of placental function on the maternal side. Adequate blood flow in the UtA is essential for maintaining normal placental function and ensuring fetal blood oxygenation in utero, which significantly impacts fetal intrauterine growth. Our study found no statistically significant differences in the RI and S/D values of the UtA between two groups, or between adverse and good pregnancy outcomes. These results suggest that early infection does not affect maternal UtA vascular remodeling.

MV-Flow technology can detect microvascular flow that is not visible with conventional Doppler imaging. It provides a detailed view of low-velocity blood flow associated with surrounding tissues, exhibiting high sensitivity and resolution. This technology has the potential to visualize microvessels with slow blood flow velocity. MV-Flow technology can visualize not only the placental villous shaft but also quantify the placental microvascular structure at the level of the villous lobe. Chen et al. [7] demonstrated that MV-Flow is the optimal method for assessing placental blood flow perfusion. Compared to other placental examination techniques, MV-Flow technology is easy to operate and fast, significantly improving examination efficiency.

Herein, we found that different tracing methods in the ROI had no significant effect on the results of measuring placental VI^MV values using the MV-Flow technique, indicating high reproducibility of the technique. The VI^MV value represents the percentage of the colored area within the placenta, indicating the density of microvessel per unit volume. Therefore, the placental VI^MV value is directly proportional to the placental blood perfusion volume, with higher VI^MV values indicating greater blood perfusion, and vice versa. There was no significant difference in placental VI^MV values measured by MV-Flow technology between the adverse pregnancy outcome group and the normal pregnancy group in this study. The results suggest that early infection does not significantly impact maternal placental blood perfusion, as there was no significant difference in VI^MV values between the positive and adverse outcome groups of early infection measured by MV-Flow technology. Additionally, SARS-CoV-2 infection in the first-trimester does not increase the risk of adverse fetal outcomes during pregnancy.

In conclusion, pregnancies affected by SARS-CoV-2-Omicron during the first-trimester do not have an increased risk of adverse fetal outcomes. Utilizing ultrafine blood flow imaging technology can effectively assess placental perfusion and provide valuable insights for clinical diagnosis and treatment. Further large-scale, prospective studies are needed to confirm these findings and to establish a definitive conclusion on this topic.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

SYY and PPZ designed the research study. ZHX and QL performed the research. XDZ and TAJ provided help and advice on the experiments. SYY analyzed the data. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki, and the protocol was approved by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine (approval number: IIT20230328A).

This project was supported by the General Research Project of Department of Education in Zhejiang Province (No. Y202353427).

The authors declare no conflict of interest.