KANET evaluation in patients with SARS-CoV-2

Introduction

COVID-19, the disease triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified as a worldwide pandemic in March 2020 [1]. The physiological changes in the cardiorespiratory and immune systems during pregnancy may make pregnant women and newborns more vulnerable to COVID-19, potentially influencing their response to the infection [2]. There are concerns that fetuses could be exposed to the virus during pivotal stages of development [3]. The impact of COVID-19 on pregnancy outcomes is not well understood, and there is a scarcity of comprehensive meta-analyses on pregnant individuals with the virus. Earlier research, often based on case reports or series, presents challenges in interpretation and could be biased [4, 5]. Findings from a 2020 systematic review indicate that pregnant individuals might not be at higher risk of contracting SARS-CoV-2 or displaying symptoms of COVID-19; however, their risk of experiencing severe symptoms is elevated compared to non-pregnant individuals [5]. Despite recent observational studies indicating possible adverse pregnancy outcomes from both symptomatic and asymptomatic COVID-19 cases, inclusive of mild to severe infections, systematic reviews synthesizing these findings are still lacking 6], [7], [8], [9], [10], [11], [12.

Historically, monitoring fetal behavior in utero has been crucial for perinatal screening. Advances in ultrasonography over the past few decades have enhanced our understanding of fetal conditions. Prenatal screenings focused on the neurological health of fetuses have provided significant insights, and recent improvements in ultrasound technology have improved the monitoring of fetal physiology in a cost-effective manner with direct visualization 11], [12], [13. The Kurjak’s antenatal neurodevelopmental test (KANET), first introduced in 2008, is a sonographic method used to assess fetal neurology and has shown high reliability in evaluating brain function and developmental progress in fetuses. However, data on the use of KANET in pregnancies affected by SARS-CoV-2 remain limited. Studies have shown that prenatal SARS-CoV-2 infection can result in neurodevelopmental and behavioral outcomes, as observed in animal models [1, 2]. This study aims to investigate fetal neurological behavior in pregnant women diagnosed with SARS-CoV-2 using the KANET test. Emerging evidence suggests that SARS-CoV-2 infection during pregnancy could lead to adverse outcomes, such as preeclampsia, preterm birth, and low birth weight. However, the impact of COVID-19 on fetal neurodevelopment remains unclear. This study aims to fill this gap by using the KANET scoring system to assess potential neurological impairments in fetuses exposed to SARS-CoV-2. The study began in December 2019, coinciding with the earliest reports of SARS-CoV-2. Although the pandemic was officially declared in March 2020, early cases were identified globally in late 2019. Initial concerns about potential effects on pregnancy outcomes prompted the early initiation of this study to investigate possible impacts on fetal neurodevelopment [12, 14].

Materials and methods

The Kurjak’s antenatal neurodevelopmental test (KANET) was chosen for this study due to its reliability in assessing fetal brain function. Introduced in 2008, KANET evaluates parameters such as isolated head, hand, and leg movements, cranial sutures, hand-to-face/head movements, finger movements, yawning, mouthing, facial expressions, and eye blinking (Figure 1). This test has shown high reliability in evaluating brain function and developmental progress in fetuses. Unlike general movement measurement or the Amiel-Tison neurological assessment, KANET provides a comprehensive sonographic method for prenatal neurological screening. Relevant literature supports its use as a reliable tool for assessing fetal neurodevelopment [5, 6].

Figure 1:

Yawning.

A total of 81 pregnant women between 28 to 40 weeks participated in the present study. Participants were subdivided into two groups. The first group (A) included 38 pregnant women with SARS-CoV-2, while the (control) second (B) group included 43 non-COVID pregnant women. The study was performed in the Department of Fetal and Maternal Medicine, of “Alexandra” Hospital, of National and Kapodistrian University of Athens in a study period of 3 years, from December 2019 to December 2022.

Results

No statistically significant differences were observed between the two groups regarding the maternal age (33±3.9 years for group A vs. 31±4.1 years for group B) and gestational age (33±1.6 weeks for group A compared to 33±2.1 weeks for group B). Performance of the KANET test varied from 8.30 am to 20.00 pm (Table 2). After analysis of the KANET results of each group, no abnormal scores were identified in both groups, while the borderline scores were both 1 while normal scores were 37 (97.4 %) and 42 (97.7 %) for groups A and B respectively. Further analysis with the KANET score showed small differences between the two groups for isolated eye blinking, facial alterations and finger movements, but no differences in each case scoring were observed (Table 3).

Discussion

The comprehensive effects of COVID-19 on gestational outcomes are yet to be fully discerned, particularly with the ongoing accumulation of new data. Potential alterations in the risk of COVID-19 due to the unique pathophysiological changes of pregnancy remain hypothetical, as there is a lack of robust data to confirm these effects. The infection’s presence during any stage of pregnancy may elevate the risk of serious illness, which in turn could lead to considerable complications and noteworthy negative outcomes in particular scenarios. Research has indicated that being infected with SARS-CoV-2 while pregnant could lead to a range of serious complications, including an increased likelihood of preeclampsia, early delivery, gestational diabetes, infants with low birth weights, and stillbirths [15–18]. Additionally, cases of pneumonia caused by SARS-CoV-2 have been connected to a spectrum of adverse outcomes, such as early onset of labor, breaking of waters before labor begins, fetal growth being inhibited, fetal loss, and even neonatal fatalities.

The CDC reports indicate that pregnant individuals are at a twofold increase in risk for ICU admissions, 2.4 times more likely to undergo extracorporeal membrane oxygenation, and have a 1.7 times greater risk of mortality due to severe illness. This group also faces a greater likelihood of hospital admittance and the necessity for oxygen supplementation and invasive ventilation [19–21]. In the U.S., a more severe progression of COVID-19 tends to affect pregnant women who are economically disadvantaged, particularly within the Hispanic community, those without medical insurance, and interestingly, those living in less crowded homes [22, 23].

Findings from the UK corroborate that black individuals, those of advanced maternal age, and those with comorbidities like obesity, respiratory diseases, high blood pressure, and diabetes before pregnancy are subject to increased danger of intense COVID-19 infection and unfavorable outcomes during and after pregnancy [24, 25]. In our investigation, we delve into the assessment of neurodevelopmental trajectories using KANET scores among pregnant women affected by COVID-19 compared to those not affected by the virus, to ascertain the feasibility of predicting deviations in fetal neurodevelopment.

Our analysis did not reveal any notable statistical variance in the score distributions between the cohorts. Moreover, the neurodevelopmental outcomes of newborns appeared unaffected by whether the mothers had contracted COVID-19 during pregnancy. Recent studies have shown varying impacts of maternal COVID-19 on fetal neurodevelopment. For instance, research indicates potential risks associated with low oxygen saturation in severe cases of COVID-19, which could affect fetal neurobehavior [26, 27]. Our findings, however, suggest no significant differences in neurodevelopmental outcomes between the COVID+ and control groups, likely due to the low-risk profile of the included cases. The lack of significant differences in KANET scores between the COVID+ and control groups suggests that SARS-CoV-2 infection during the third trimester may not be associated with altered fetal neurodevelopment. However, the relatively small sample size and the predominance of mild COVID-19 cases may limit the generalizability of these findings. Further studies with larger cohorts and a broader range of COVID-19 severity are necessary to confirm these results.

There are some limitations to be stated considering our study. When SARS-CoV-2 infection was initially detected, our study protocol was designed with the hypothesis of evaluating patients with pneumonia who were at high risk for being infected by this new virus, especially those who had been in Asia or came in contact with Asian tourists in the preceding three months. It was not until February 2020, when the World Health Organization (WHO) officially announced SARS-CoV-2 as a global threat and PCR testing became the gold standard for COVID-19 detection, that we adapted our protocol to specifically focus on COVID-19 during pregnancy.

Additionally, one of the main limitations of our study is the absence of patients with severe COVID-19 symptoms. Our hospital was not responsible for treating pregnant patients with severe COVID-19, and such cases were either transferred to the designated hospital or did not reach our clinic. As a result, all COVID-19 positive cases included in this study were either asymptomatic or presented with mild to moderate symptoms (fever, cough, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea, or vomiting). This limitation has also influenced the sample size and the characteristics of the COVID-19 group in our study. Furthermore, there were no reports of neonatal COVID-19 infection with severe symptoms in our study cohort, a significant factor contributing to the relatively small sample size of 38 pregnancies in the COVID-19 group.

These limitations should be considered when interpreting the findings, as the absence of severe cases means that our results may not be generalizable to all pregnant women with COVID-19, particularly those with severe symptoms.

Conclusions

With the development of 4D ultrasonography, the KANET scoring system [20] has been created. It is the first ultrasound scoring system to measure prenatal neurological behavior for routine screening [21]. Other studies have previously used KANET scoring system in order to evaluate fetal neurological behavior in low- and high-risk gestations. All investigations revealed substantial differences between high- and low-risk groups in prenatal neurological functioning. In addition, abnormal prenatal KANET scores were related with impaired neurobehavioral development [8]. In our study, maternal SARS-CoV-2 was not correlated with aberrant fetal neurological behavior. The research was restricted by the small sample size and the absence of a link between prenatal neurological abnormalities and postnatal neurological outcomes. Future research on a bigger patient sample is required to link prenatal and neonatal data in order to increase our knowledge of the influence of maternal SARS-CoV-2 infection on the neurological health of infants.