Correlation of Nutritional Status with SomeMicronutrients in Children with Ventricular Septal Defect

The aim of this study was to explore the association between the BMI Z score and the levels of some selected common...

industrialization and urbanization has changed the environment.
Increasing numbers of women have postponed childbearing age, especially in developed countries, leading to a high incidence of congenital abnormalities. The incidence of congenital heart disease is increasing each year, so studies of congenital heart disease are receiving increased attention.
Due to the abnormal hemodynamics caused by congenital heart disease, children with congenital heart disease often suffer from hypoxia, hyperthyroidism, frequent respiratory infections, and poor gastrointestinal absorption [3], and growth retardation and malnutrition are common in children with congenital heart disease.

At present, the European Society of Pediatric Gastrointestinal
Hepatology Nutrition has called for the establishment of a "nutrition support team (NST)" aimed at scientifically effective nutritional management of hospitalized children and reduction of the prevalence of malnutrition [4]. However, with the trend in younger children with congenital heart disease becoming increasingly obvious [1], the earlier the time for surgery is, the more favorable it is for children to catch up with children of the same age earlier in their growth and development [5]. Therefore, we should focus our attention and intervention on the nutritional status of children with congenital heart disease.
However, clinical interventions for nutrition are mostly focused on carbohydrates and fats that can provide actual calories, and the importance of micronutrients is often overlooked. Although humans need a few vitamins and trace elements, they are the trace organics necessary for maintaining body health. These substances neither provide energy sources in the body nor constitute the raw material of body tissues or participate in the formation of human cells; however, these substances play a crucial role in the growth, metabolism, and development of the human body. Due to a lack of attention to dietary supplements and poor digestive functions such as malabsorption and diarrhea, children with congenital heart disease are at risk of these micronutrient deficiencies. In addition, diuretics are used in children with congenital heart disease.
Diuretics excrete water and sodium through the kidneys to improve circulatory function and at the same time, excrete other watersoluble molecules, including potassium, magnesium, and vitamin C [6]. Studies have shown that early identification of abnormalities in micronutrients and immunodeficiency can help reduce the incidence in children after cardiac surgery [7].
It is necessary to carry out studies of the preoperative nutritional status of children with congenital heart disease, especially infants and young children, and investigate the correlations between nutritional status and various common trace elements and vitamins in our country. Studies have shown that the nutritional status of children with cyanotic and noncyanotic congenital heart disease is significantly different: children with noncyanotic congenital heart disease are more prone to malnutrition [8], and the nutritional status of these children and its influencing factors deserve more attention. Ventricular septal defect is the representative disease type in noncyanotic congenital heart disease. It is the most common clinical congenital heart disease, accounting for approximately 20% of congenital heart disease [9]. Therefore, in order to ensure the representativeness of the research sample and effectively control for confounding, this study selected ventricular septal defect as the research disease. This research will study the preoperative nutritional status, common elements, and vitamin levels of children with ventricular septal defect younger than 5 years of age and explore the relevance between them, so that we can provide preventive measures for preoperative malnutrition and guide postoperative nutritional intervention.

The study was approved by the Ethical Committee of Children's
Hospital of Nanjing Medical University, and informed consent was obtained from the guardian of the children.

Nutrition Evaluation Method
Anthropometric measurements included weight (kilograms) and length (centimeters), and they were performed according to standard World Health Organization (WHO) procedures [10]. The Z-score method provided by the National Health Statistics Center and recommended by the WHO was used as the evaluation standard. The Z-score was calculated according to the formula Z-score=(measurement value-median value of the same-age and same-sex reference standard)/standard deviation of the reference standard, including height for age Z-score (HAZ), weight for age Z-score (WAZ), and weight for height Z-score (WHZ). The latest WHO reference standard in 2006 was selected to calculate the Z value [11].

Data Analysis
In this study, SPSS 23.0 statistical software was used for statistical analysis, and P<0.05 indicates a significant difference.
General information, zinc, iron, magnesium, copper, calcium, VA, VB1, VB2, VB6, VB9, VB12, VC, VE, and VD levels of male and female children are described with the mean plus standard deviation.
Mann-Whitney U tests verified whether there was a significant difference between different genders. Pearson bivariate correlation analysis was used to evaluate the correlation between Z scores (e.g., WHZ, WAZ, HAZ) and Zn, Fe, Mg, Cu, Ca, VA, VB1, VB2, VB6, VB9, VB12, VC, VE, and VD. Z-values WHZ, WAZ, and HAZ were grouped by 0, and we compared the levels of Zn, Fe, Mg, Cu, Ca, VA, VB1, VB2, VB6, VB9, VB12, VC, VE, and VD between groups, verified whether they met normality and used an independent t-test for data that satisfied normality. If the data did not satisfy normality, the Mann-Whitney U test was used. Using logistic regression analysis, the confidence interval level was 95%. After correction for age, gender, and pulmonary artery pressure, the ratios of Z-values WHZ, WAZ, HAZ and zinc, iron, magnesium, copper, calcium, VA, VB1, VB2, VB6, VB9, VB12, VC, VE, and VD were analyzed, and the 95% confidence interval was calculated.

Demographic Characteristics of the Participants
There were 68 females and 78 males; for females, the mean age was 18.75±17.75 months, mean weight was 9.97±5.15 kg, and mean height was 78.16±18.33 cm, and for males, the mean age was 21.33±18.56 months, mean weight was 11.13±5.20 kg, and mean height was 81.46±18.07 cm. The iron levels of females were significantly higher than those of males (male vs female: iron, 415.03±33.80 vs 427.87±38.33, P=0.033) ( Table 1). However, no statistically significant differences of other vitamins and trace elements were existing in males and females.

Correlation Analysis of Elements and Vitamins and Z Scores
Pearson correlation analysis (  (Table 3). As a result, we conducted a linear regression after adjusting gender and age and found VC was positively associated with between WAZ. The P value was 0.035, as shown in (Figure 1) and (Table 4).  Figure 1: A scatter plot and a fitted line with 95% CI of the relationship between vitamin C and weight for age Z-score in children with ventricular septal defect.   Substances are Log10 Corrected gender, age, pulmonary artery pressure.

Discussion
The results of our study revealed a linear regression relationship between VC and WAZ, with a P value of 0.035, suggesting a possible correlation between VC and the nutritional status of children with congenital heart disease. In people with malnutrition caused by chronic diseases, poor eating habits, malabsorption, and other factors, obvious VC deficiency can often be seen [12]. Some animal experiments have shown that VC is an important vitamin for maintaining normal growth and physiological function [13], playing an important role in the growth process [9], collagen formation [14,15], iron metabolism and hematology [9], reproduction [16], stress response [17], and wound healing [18]. Wang et al. [19]. found that dietary supplementation with VC can significantly increase the daily weight of juvenile ducks. A study by Zhou et al. [20] also showed that increases in body weight, specific growth ratio, protein efficiency ratio, and feed efficiency of VC-deficient fish were lower than those of fish supplemented with VC. In addition, growth performance, antioxidant capacity, and humoral immune parameters of juvenile cobia supplemented with VC were significantly improved [19,20].
Heart failure increased pulmonary arterial pressure, and anemia are risk factors for protein energy malnutrition in children with congenital heart disease [9], and some physiological functions of VC can alleviate these risk factors. A considerable amount of research is currently focused on the use of VC to prevent heart failure [21], mainly because of its ability to prevent oxidative damage. Reactive oxygen or nitrogen species (ROS/RNS) are the most common oxidants in the human body and play a key role in aggravating human heart failure [9]. Studies have shown that ROS and RNS can change the properties of lipids, proteins, and nucleic acids, leading to myocardial dysfunction, and myocardial oxidative damage is closely related to congestive heart failure [22].
On the other hand, ascorbate regulates vasodilation by increasing NO synthesis and improving bioavailability [23]. Endothelial NO synthase (eNOS) produces NO, which then diffuses into the smooth muscle cell layer of the vascular wall and causes vasodilation through interaction with soluble guanylate cyclase. Another clinical application of VC is to increase the absorption of nonheme iron [12]. In summary, we speculate that VC can indirectly influence the nutritional and growth status of children with congenital heart disease by exerting its biological functions.
VC is mainly related to WAZ, which can reflect acute malnutrition in patients, and we have previously speculated that some trace elements may be related to HAZ, reflecting chronic malnutrition in patients. However, in our research, no correlation was found be-

Conclusion
This study revealed a positive correlation between VC and the nutritional status of children with ventricular septal defects. Further, our results may have implications from the perspective of VC on the nutritional status of children with clinical congenital heart disease intervention, to prevent malnutrition in children before surgery, while guiding clinical staff to carry out postoperative nutritional support in children with congenital heart disease.