We used the “Confidence Intervals for Kappa” in PASS15 software to estimate the sample size of this study. According to clinical experience and pre-experimental results, the kappa coefficient is about 0.806, and its standard deviation is 0.12. If the class I error of the relevant parameters is set as 0.05 (α = 0.05) with an allowable error of 0.05 (δ = 0.05), the calculated sample size is 89 children. With the addition of 10% sample loss, at least 98 patients are required.

Premature infants who were hospitalized in the Department of Neonatology, Children's Hospital Affiliated to Chongqing Medical University from September 2022 to March 2023, and needed PICC catheterization were selected as the study subjects. The inclusion criteria were as follows: premature infants requiring PICC catheterization; the physical condition of the infant able to withstand US examination; the bleeding and clotting time being normal; no serious contraction or collapse of peripheral blood vessels; PICC retention time >1 week; and parents are informed and signed informed consent. The exclusion criteria were as follows: congenital heart disease or other cardiovascular diseases; immunodeficiency disease; severe intestinal inflation, unable to determine the position of catheter tip; the local skin of the ultrasonic observation window being incomplete, with skin lesions or infection; and transfer, abandonment of treatment, or death. This study was approved by the hospital ethics committee (2022-369); Clinical trial registration number (ChiCTR220064003).

PICC placement was performed by two nurses with PICC operation qualification. Briefly, the neonate was placed in an incubator. Catheterization was performed with a puncturing kit containing 26 GA (1.9 F) single-lumen PICC catheters according to the neonatal PICC catheterization operation specifications.

According to the specifications, it should be avoided placing the catheter tip in the heart of neonates and infants (15). The optimal tip position complied with the recommendation of the 2016 guidelines by the American Infusion Nurses Society (INS), i.e., the safest PICC tip should be located within the lower third of SVC or just below the IVC-and-right-atrial junction (3, 18, 19).

US is conducted under a LOGIQ e color Doppler ultrasonic diagnostic system (6S and 8C probes, GE company, USA) by two research members who have at least 5 years of experience in ultrasonic PICC positioning. The ultrasonic probe was set at the midline of the subxiphoid region or at the parasternal line of the right subclavicle region. A hyperechoic “equal sign'-like or sandwich-like structure would be detected within the vena cava, which represents the inserted line. In detail, for clearly viewing the “equal sign” like echoes of the catheter tip in SVC, the probe was placed longitudinally at the 2nd−3rd intercostal spaces on the right of the sternum to delineate the long axis of the aortic arch and the short axis of SVC and then rotated clockwise for about 15° and tilted slightly to the right to show the long axis of SVC and the right atrial entrances of SVC and IVC (Figure 1A). Subsequently, the distance between the tip and the right atrial inlet was measured, and improper tip position was US-guided readjusted. For clearly viewing the “equal sign”-like echoes of the catheter tip in IVC, the probe should be placed longitudinally at the midsagittal position of the subxiphoid region and scanned along the inferior rib to delineate the IVC and right atrial inlet (Figure 1B). The tip-to-atrium distance was measured, and improper tip position was readjusted.

The puncture site, the distance between the catheter tip and the right atrium inlet, was measured under US on the day of catheterization and every other week after catheterization. Recording the weight and length at the time of the PICC catheter was done every week, and the increase in weight and length after inserting the PICC catheter was calculated. To calculate the correlation between the increase in weight and length of premature infants and the displacement distance of the PICC tip, all data were entered by two PICC specialist nurses, and the results with differences were reviewed and agreed upon by two people. Two people will input all data into the computer, and all electronic data will be checked by a third person.

In this study, SPSS 24.0 software was used to statistically process the data. The counting data is expressed in cases and percentage (%). The measurement data conforming to normal distribution are described by mean ± standard deviation, and the measurement data of non-normal distribution are expressed by median and quartile spacing; The correlation between weight gain and length growth and PICC tip shift was analyzed by the Spearman rank correlation analysis, and a P-value of < 0.05 was considered to be a statistically significant difference.

A total of 1,816 newborn infants were screened between September 2022 to March 2023, of which, 1,606 did not meet inclusion criteria, including 873 of gestational age (GA) ≥ 37 weeks; thus, 598 PICC catheters were not used, 109 parents of preterm infants declined to participate, and 26 are excluded for other reasons. Finally, 210 premature infants enrolled, of which eight of them dropped out (seven were transferred to another department and one abandoned treatment). Finally, 202 finished the study before and after self-control trials and were included in the final analysis (Figure 2). The number of involved preterm infants reached the calculated sample size.

Of the included neonate, 121 were boys and 81 were girls. A total of 69 cases received invasive mechanical ventilation, 101 received non-invasive mechanical ventilation, and 32 were not on a ventilator. Upper limb catheterization was performed in 11 cases, including one case of the superficial temporal vein, eight cases of the basilic vein, and two cases of the cephalic vein. Lower limb catheterization was performed in 191 cases, including 128 cases of great saphenous vein and 63 cases of superficial femoral vein. The mean gestational age was (31.75 ± 2.83) weeks, the age at the time of catheterization was (3.09 ± 7.46) days, and the weight on the day of catheterization was (1,758.54 ± 591.58) g.

The results showed that the PICC catheterization time was 15 days, with a weight gain of 230 g and a length growth of 1 cm. The catheter tip displacement was 0.33 and 0.09 cm, as shown in Table 1. From the time of catheterization to the 3rd week, the weight gain was 451 ± 178 g, the length growth was 1.50 (1.00–2.12) cm, and the catheter displacement was 1.27 ± 0.89 cm. By the fifth week, the weight gain was 750 (715–975) g, the length growth was 3.00 (2.00–3.7) cm, and the catheter displacement was 2.23 ± 0.95 cm. The weight and length growth during the catheterization period is shown in Figures 3A, B, respectively. The tip displacement distance in each week in the flexion position was −0.06 ± 0.79, 0.57 ± 0.41, 0.76 ± 0.20, 0.36 ± 0.23, 0.58 ± 0.52, and 0.32 (0.17–0.57) cm; in the straight position, it was −0.31 ± 0.77, 0.51 ± 0.30, 0.62 ± 0.20, 0.36 ± 0.29, 0.43 ± 0.17, and 0.35 ± 0.18 cm, as shown in Figure 3C. The tip displacement in the flexion and straight positions from the beginning of catheterization was −0.06 ± 0.79, 0.51 ± 0.88, 1.27 ± 0.89, 1.64 ± 0.82, 2.23 ± 0.95, 2.64 ± 0.84 cm and 0.31 ± 0.77, 0.20 ± 0.91, 0.82 ± 0.80, 1.18 ± 0.87, −1.62 ± 0.93, 1.98 ± 0.85 cm, respectively, as shown in Figure 3D. In the first week, 134 (66.33%) of the flexion position and 153 (75.74%) of the straight position were displaced to the heart direction, 0.37 (0.26–0.56)/0.66 (0.45–0.87) cm respectively. The fluctuation of the data of catheter tip displacement distance measured in different positions showed that the tip displacement distance was 0.23 (0–0.97) cm in flexion position and 0.25 (0–0.98) cm in the straight position from the second week. The small fluctuation range in the flexion position indicates that the stability of the flexion position is higher. There were five patients with edema. After the edema subsided, the catheter tip was tracked and found to be displaced 1.04 ± 0.24/1.43 ± 0.17 cm in the flexion and straight position of the catheter tip to the heart direction in the first week.

Using the Spearman rank correlation analysis, different positions had different correlations between the distance of catheter tip displacement and weight gain. The correlation coefficient in the flexion position was r_s= 0.681, with a P-value of < 0.05, and r_s= 0.661, with a P-value of < 0.05 in the straight position, indicating a significant correlation between the two positions as shown in Figures 4A, B. The correlation between the distance of catheter tip displacement and length growth was also different, with r_s= 0.629, a P-value of < 0.05 in the flexion position and r_s= 0.617, a P-value of < 0.05 in the straight position, indicating a significant correlation between the two positions as shown in Figures 4C, D. This suggests that the correlation between the distance of catheter tip displacement and weight gain is higher, especially in the flexion position.

Due to the catheter displacement being highly likely to occur due to natural growth, and the rate of PICC ectopia can be as high as 35% due to factors such as blood flow dynamics and positional changes (20). We found that 100% of premature infants' catheter tips were affected by positional changes in veins with changes in body position and blood flow. After 1 week of placement, we found that the tips of 134 (66.33%)/153 (75.74%) cases are closer to the heart than at placement. This is consistent with Srinivasan's finding that 32.6% of PICC catheters move toward the heart 24 h after placement (21). With the rapid increase in weight and body length, the catheter tip not only did not move away from the heart but also moved closer to the heart. This may be due to catheter bending or folding during placement, followed by flushing with blood flowing toward the heart, resulting in catheter movement toward the heart. Therefore, even after the initial catheter placement is in the ideal position, there is still a high possibility of catheter tip displacement into the heart cavity. Studies have shown that the incidence of PICC-related arrhythmias is 1%, which can lead to the death of children; most arrhythmias occur within the first 2 weeks after insertion of the catheter (22). Therefore, it is essential to use US tracking to determine whether catheter withdrawal is needed 1 week after placement. In addition, for edematous infants, the catheter tip was tracked after the edema subsided, and it was found that the tips of the catheter moved toward the heart. The appearance and disappearance of edema can lead to catheter tip placement that is too shallow or too deep and may enter the atrium. Therefore, US should be used to locate the catheter in a timely manner after edema subsides to determine whether catheter withdrawal is needed. If the tip of the catheter enters the heart, the position would be adjusted. To do this, US was used to measure the length of the catheter tip that has entered into the heart. Then, adjust the tip to the entrance of the atrium, and make a record of the adjustment.

This study showed that the tip of the catheter moved to different degrees with the increase in weight and length and was significantly correlated with weight gain and length growth (r_s = 0.681/r_s = 0.629), with a higher correlation with weight gain. Therefore, assessing weight gain is a more accurate predictor of catheter displacement. The ideal position of PICC is the upper and lower thirds of the vena cava. The length of the SVC in preterm infants is only 2–3 cm, while that of IVC is 4–5 cm (18). Therefore, the maximum limit of the ideal position is 1 and 1.67 cm for the SVC and IVC. The results of this study showed that by the third week, the catheter had moved 1.27 ± 0.89 cm, and the catheter of the SVC had moved out of the ideal position. By the fifth week, the catheter had moved 2.23 ± 0.95 cm, and the catheter of the IVC had moved out of the ideal position. At this point, the catheter was considered to have reached the stage where it must be repositioned. If the catheter is left in place and fluid is infused, the inadequate blood flow velocity in the non-central vein can result in insufficient drug dilution, and the high osmotic and high concentration liquid can corrode the venous wall, leading to complications (23, 24). Therefore, catheter displacement should be closely monitored starting from the third and fifth weeks after placement. If timely repositioning is not possible, the safety of the catheter can be confirmed by withdrawing blood, flushing the catheter, and reducing the osmotic pressure of the nutrient solution. Tracking the catheter tip position predictively and removing high-risk catheters as early as possible can maximize the prevention of complications (25, 26), which is also consistent with Costa's view that complications of central venous catheters can be prevented (27).

The correlation between PICC tip displacement in flexion/straight positions and weight gain/length growth differed in this study. The correlation was higher in the flexion position; therefore, positioning in the flexion position is recommended. Additionally, from the second week onwards, the tip displacement in the flexion position was 0.23 (0–0.97) cm, while in the straight position, it was 0.25 (0–0.98) cm. Thus, the displacement in the flexion position was smaller, consistent with the correlation results, and positioning in the flexion position is also recommended. Tauzin et al. used US to locate the PICC tip and recommended fixing the position to improve accuracy (7). Therefore, the influence of posture should be fully considered, and the positioning posture should be fixed as the flexion position.