Leczenie żywieniowe noworodków w stanie krytycznym: mieszanki pół-elementarne jako metoda żywienia dojelitowego

Dmytro Shkurupii1,2

1 Separate division of the Association of Anaesthesiologists of Ukraine in the Poltava region, POLTAVA, UKRAINE

2 Higher State Educational Institutor of Ukraine «Ukrainian Medical Stomatological Academy», Poltava, Ukraine

ABSTRACT

Introduction: The goal is to increase the efficiency of nutritional support in intensive care of newborns by substantiating the choice of the enteral blend.

Materials and methods: A prospective cohort study was conducted, which included 173 newborns. The main group consisted of 143 patients of intensive care units. The comparison group – 30 virtually healthy newborns. Physical parameters, changes in protein metabolism, serum immunoglobulins, functioning of the gastrointestinal tract and hepatobiliary system in the development of critical conditions and depending on the type of enteric urine formula were determined.

Results: At the beginning of newborn enteral nutrition in the main group, (46.15% of cases), there were signs of gastrointestinal malformation, distributions were detected in protein metabolism, decreased serum immunoglobulin fractions, gastroduodenal cytoprotection, increased alkaline phosphatase activity. Against the background of the use of semi-elemental hydrolysable formulas a greater frequency of excretions was observed, the assimilation orientation of protein metabolism, increased levels of serum immunoglobulin fractions, reduction of gastroduodenal cytoprotection, reduction of laboratory characteristics cholestasis and damage to hepatocytes.

Conclusions: In newborns in critical conditions, adaptation to the onset of enteral nutrition is accompanied by a catabolic direction of metabolism. The use of semi-elemental formulas increases the efficiency nutritional support in the intensive care of newborns.

Wiad Lek 2018, 71, 2 cz. II, -270

 

INTRODUCTION

Gastrointestinal malnutrition is a frequent pathological syndrome in patients with intensive care units, which results in a violation of physiological nutritional intake [1].

The World Health Organization declares that adequate nurturing of children should not only be a means of covering current protein and energy needs, but also a factor in the growth, development and formation of adaptive body responses [2]. Given the high metabolic needs, newborns requiring intensive care are the most vulnerable contributor of patients in the development of nutritional deficiencies [3].

Breast milk is the optimal baby food, but the number of babies in critical conditions that receive artificial nutrition formulas remains high [4].

The purpose of this study was to increase the effectiveness of nutritional support in the intensive care of newborns by substantiating the choice of the enteral blend.

MATERIALS AND METHODS

A prospective cohort study was conducted, which included 173 newborns aged 0 days to 27 days. Before conducting research, legal representatives of patients received written statements of informed consent to participate in the study. The study was approved by the local bioethics committee and was in line with the principles set out in the Helsinki Declaration, with further additions.

The main group consisted of 143 newborns who were treated at the intensive care unit for postponed asphyxia at birth (heading P21: Asphyxia at birth). The length of stay on the bed of intensive care was 11 ± 2.3 days.

The comparison group consisted of 30 children of the same age group who had an infantile perinatal history, were naturally nourished, and their overall condition was considered satisfactory.

Changes in protein metabolism, immune status, functioning of the gastrointestinal tract and hepatobiliary system were determined in the development of critical conditions and depending on the type of enteric urine formula. The effectiveness of the semi-elemental hydrolyzed formulas with the protein component in the form of di- and tripeptides (n = 83) and adapted formulas containing serum and casein proteins (n = 60) was compared. The study used the data of a physical examination, determination of body mass dynamics, results of laboratory tests:

1) the levels of total protein and albumin in serum were determined by the unified method by the diagnostic sets of the Agat Company (Russia);

2) the content of the γ-globulin fraction of serum proteins was determined by its allocation by electrophoresis on paper;

3) the level of serum immunoglobulins (Ig) A, M and G diagnostic kits for the immuno-enzymatic analysis of the firm “B.A.T.- BioAnalysis Technologies” (Ukraine);

4) Nitrogen balance (NB) was calculated for the difference in nutrient intake of nitrogen and its loss due to the daily excretion of urea, the level of which was determined by the unified method by the diagnostic sets of the firm “Filsit Diagnostika” (Ukraine);

5) the level of serum glycosaminoglycans (GAG) was determined by the Orcine method using the company’s “Di-M” reagents (Russia);

6) The activity of alkaline phosphatase in serum was determined by the method of hydrolysis of p-nitrophenyl phosphate by the diagnostic kits of the firm “Filsit Diagnostika” (Ukraine).

Statistical processing of the results was carried out using the Microsoft Office Excel 2003 software package. The description of the results of the study used the calculation of the arithmetic mean (M), the representativeness errors (m). The comparison of the two groups was performed by calculating Student’s criterion for absolute indices and Pearson’s χ2 criterion for relative indices. When carrying out statistical data processing at the minimum level of error-free prediction, Р = 0,95 was considered and, accordingly, for the probability level of the error – р ≤ 0,05.

RESULTS

At the time of intensive care, at the moment of starting the EC initiation, 66 newborns (46.15% of cases) experienced abdominal distension, and 55 children (38.46% of cases) had a delay in the evacuation of gastric contents on the first day of the EC. In healthy newborns, these events were not observed (χ2= 29.1 and χ2 = 36.8, respectively, p < 0.05).

Ill newborns’ level of albumin, γ-globulins and individual Ig classes in serum was lower in early serum than in healthy newborns, which was reflected in the overall blood protein index (Table I).

At the beginning of the enteral nutrition, an increase in the activity of alkaline phosphatase in the blood serum of newborns in the main group was found, in which this figure was 743.73 ± 61.55 nmol / s / l, whereas in the children of the comparison group – 568.89 ± 58, 74 nmol / sec / l (p < 0.05).

The level of GAG in the newborns of the main group at the beginning of the enteral nutrition was 0.203 ± 0.012 g / l versus 0.046 ± 0.005 g / l in the comparison group (p < 0.05).

Subsequently, the effectiveness of nourishing newborns was determined, depending on the type of enteral formula. Meteorism in newborns receiving hydrolysis formulas were noted in 39.75% of cases (n = 33), and in newborns who received adapted formulas in 58.33% of cases (n = 35) (χ2 = 4.81; p < 0.05). The frequency of delayed evacuation of the gastric contents did not differ significantly depending on the type of enteric formula and was 39.75% (n = 33) in newborns receiving semi-elemental formulas and 41.67% of cases (n = 25) in newborns who received adapted formulas (χ2 = 0.05; p > 0.05). The frequency of defecation in newborns receiving semi-elemental formulas was significantly higher than that of newborns who received adapted formulas. In the first it was 5,07 ± 0,32 defecation per day, in the latter – 3,38 ± 0,48 defecation per day (p < 0,05).

Data on the state of protein metabolism in infants under intensive care depending on the type of enteral formula and relatively healthy newborns are given in Table II. These data demonstrate a tendency towards optimization of protein supply in newborns under intensive care with the use of semi-cellular hydrolysates.

In the group of newborns who received semi-elemental formulas during intensive care, the level of NB was + 0.41 ± 0.09 g of nitrogen / day and was positive in 79.51% of patients (n = 66), while among newborns. The average NB score was -0.236 ± 0.312 g of nitrogen / day and was positive only in 38.33% of children (n = 23) (χ2 = 25.1; p < 0.05).

A similar tendency was observed in the study of body mass dynamics. In newborns who used semi-elemental formulas, body mass index was 1.97 ± 1.01 g / kg / day and was positive in 57.42% of cases (n = 46), while in newborns who were adapted formulas, body mass dynamics was 0.07 ± 1.89 g / kg / day and was positive in 38.33% of cases (n = 23) (χ2 = 4.1; p < 0.05).

Activity investigations of serum liver enzymes showed a significant low activity of alkaline phosphatase in newborns who received hydrolyzable formulas compared with a group of newborns who were prescribed adapted formulas. The enzyme activity of the group was 620.57 ± 30.88 nmol / s / l, while in others it was 823.86 ± 64.24 nmol / s / l (p < 0.05). At the same time, the level of alkaline phosphatase in the newborns receiving semi-elemental formulas did not differ significantly from that in healthy children (p> 0.05) and significantly differed in the newborns who received the adapted formulas
(p < 0.05).

The content of GAG in newborns receiving semi-elemental hydrolyzate was lower and was 0.11 ± 0.007 g / l versus 0.15 ± 0.015 g / l in a newborn group receiving formulas based on cow’s milk. In infants in critical conditions, regardless of the type of enteral formula, GAG level compared to a group of practically healthy children did not completely normalize (p < 0.05 relative to the comparison group).

DISCUSSION

The presence of violations of the gastrointestinal tract in newborns who needed intensive therapy indicates the formation of gastrointestinal malnutrition as a component of critical states [5].

Significant dissimilational shifts in protein metabolism were detected in comparison with practically healthy newborns. Similar changes in serum proteins are most likely due to a violation of intestinal absorption and the protein synthesis of the liver due to tissue hypoxia, ischemia and energy deficiency [6].

In addition, newborns in critical conditions had a decrease in the fractions of immunoglobulins, which are functional immune proteins. This coincides with the previously obtained data on immune dysfunction in newborns in connection with the formation of gastrointestinal insufficiency [7].

Changes in markers of the cytoprotective system of the mucous membrane of the gastroduodenal zone, which are GAG, were discovered. Their increase in the newborns of the main group relative to the comparison group gives reason to think about the tension of the system of protection of the mucous membrane of the stomach and duodenum [8].

At the enteral nutrition beginning the increased activity of alkaline phosphatase was found in the serum of patients with newborns, which is a marker of severity of cholestasis and hepatocyte cell wall damage [9].

The frequency of defecation in newborns receiving semi-elemental blends was significantly higher than in children who received formulas based on cow’s milk. There is evidence that intestinal motility in infants is slowed down, which is obtained in a formula with casein content [10]. In view of this, it can be argued that the semi-elemental formulas can be used in cases where undesirable inhibition of intestinal motility.

Newborns who were adapted formulas in intensive care had relatively low rates of protein anabolism were maintained: the levels of albumin and γ-globulins did not recover to the level of these parameters in the comparison group, NB had a negative tendency, the rates of body weight gain were lower than among children, who received semi-elemental formulas.

When applied, the adapted formulas retained high activity of alkaline phosphatase compared to the comparison group and the tension of the cytoprotective system of the mucous membrane of the gastroduodenal zone, manifested by the high level of serum GAG.

The use of semi-elemental formulas optimized the protein metabolism. Changes in γ-globulins occurred due to the main components of this fraction – Ig. In the group of children receiving semi-elemental formulas, compared with the newborns who received adapted formulas, the levels of Ig grades A and G. were higher than those in the group receiving formulas. Although in both groups (with the exception of Ig A levels in children receiving semi-elemental formulas), all three the classes of Ig relative to the comparison group remained significantly lower.

Due to the prescription of the semi-elemental hydrolyzates there was a retention of nitrogen, manifested by an increase in absolute values and the frequency of the formation of positive NB. A similar tendency was observed in the study of body mass dynamics. Probably the stimulation of protein metabolism is due to the high protein content of the semi-elemental formulas, as well as the presence of di-tripeptides that are easily absorbed in the intestine without the need for active transport [11].

Investigations of serum liver enzymes showed a significantly low activity of alkaline phosphatase in newborns who received a hydrolysed formula, compared with a group of children who were prescribed adapted formulas. This indicates a greater degree of cholestasis due to the application of adapted formulas.

The GAG content of newborns receiving semi-elemental hydrolyzates was lower than in the group of newborns who received adapted formulas, indicating less functional load on the gastric mucosa against the background of the use of semi-elemental hydrolyzates.

The obtained data testify to the greater efficiency of the semi-elemental formulas in newborns who require intensive care, which coincides with the opinion of other authors [11, 12].

Despite the greater effectiveness of the semi-elemental hydrolyzates during the enteral nutrition of newborns in critical conditions, the levels of protein metabolism and cytoprotection of the mucous membrane of the gastrointestinal tract did not reach the level of these indicators in virtually healthy children. That is, in conditions of intensive therapy it is only possible to achieve the tendency to normalize the protein metabolism and the functioning of the mucous membrane of the gastrointestinal tract. Adequate state of these parameters is not completely restored, which requires their correction at subsequent stages of treatment.

CONCLUSIONS

1) Newborns in critical conditions had the adaptation to the onset of enteral nutrition accompanied by a catabolic direction of metabolism, manifested by a significant reduction in serum albumin and γ-globulins, functional disorders of the motor and evacuation function of the gastrointestinal tract, the tension of the cytoprotective system of the mucous membrane of the gastroduodenal zone, the formation of signs cholestasis.

2) The use of adapted formulas based on serum proteins and casein with intensive therapy of newborns reduces the efficiency of enteral nutrition. When using these formulas, there are significantly lower indicators of protein supply, high serum content of markers of functional loading of the cytoprotective system of the mucous membrane of the gastroduodenal zone – glycosaminoglycans and the marker of cholestasis – alkaline phosphatase.

3) The use of semi-elemental formulas in intensive care of newborns can reliably restore the serum levels of albumin and γ-globulins, reduce the activity of alkaline phosphatase to the levels of this indicators that children have being in satisfactory condition, reduce the degree of functional load on the cytoprotective system of the mucous membrane of the gastroduodenal zone, accelerate the rate of mass gain the body, stimulates the motor function of the intestine and promotes the formation of a positive nitrogen balance.

4) Taking into account the inadequate recovery of protein metabolism and maintaining the tension of the gastroduodenal cytoprotective system in newborns under intensive care regardless of the type of enteral blend, further correction of these disorders should be carried out when transferring the child to the general hospital.

REFERENCES

1. Pironi L, Arends J, Baxter J, et al. ESPEN position paper. Definition and clas- sification of intestinal failure in adults. Clin Nutr. 2015; 34(2):171-80.

2. WHO. Infant and young child feeding: Fact sheet. 2017 [Electronic resourse].- Access mode: http://www.who.int/mediacentre/factsheets/fs342/en/.

3. Ditzenberger G. Nutritional support for premature infants in the neonatal intensive care unit. Crit Care Nurs Clin North Am. 2014; 26(2):181-98.

4. Carlson S, Wojcik B, Barker A, Klein J. Guidelines for the Use of Human Milk Fortifier in the Neonatal Intensive Care Unit [Electronic resourse].- Access mode: https://uichildrens.org/health-library/guidelines-use-human-milk-fortifier-neonatal-intensive-care-unit.

5. Danielle LM Hawthorne KM,   Moore CE. Growth of Infants with Intestinal Failure or Feeding Intolerance Does Not Follow Standard Growth Curves Journal of Nutrition and Metabolism. 2017; (2017): 1-6.

6. Soleimanpour H,  Safar S Rahmani F,  Nejabatian A,  Alavian SM. Hepatic Shock Differential Diagnosis and Risk Factors: A Review Article. Hepat Mon. 2015; 15(10).

7. Kholod DShkurupii DSonnik E. Immune changes in newborn infants with gastrointestinal failure requiring intensive care. Georgian Med News. 2016; 7-8 (256-257): 62-6.

8. Bimczok D, Grams GM, Stahl RD, Waites KB. Smythies LE, Smith PD. Stromal Regulation of Human Gastric Dendritic Cells Restricts the Th1 Response to H. Pylori. Gastroenterology. 2011; 141(3): 929–938.

9. Siddique A, Kowdley KV. Approach To A Patient With Elevated Serum Alkaline Phosphatase. Clin Liver Dis. 2012; 16(2): 199–229.

10. Savage KKritas SSchwarzer ADavidson GOmari T. Whey- vs casein-based enteral formula and gastrointestinal function in children with cerebral palsy. JPEN J Parenter Enteral Nutr. 2012; 36(1 Suppl):118S-23S.

11. Alexander DD Bylsma LC, Elkayam L, Nguyen DL. Nutritional and health benefits of semi-elemental diets: A comprehensive summary of the literature. World J Gastrointest Pharmacol Ther. 2016; 7(2): 306–319.

12. Mino G, Ochoa JB, Periman S. Formula Switch Leads to Enteral Feeding Tolerance Improvements in Children With Developmental Delays. Glob Pediatr Health. 2016; 3.

ADDRESS FOR CORRESPONDENCE

Dmytro Shkurupii

Separate division of the Association of Anesthesiologists

of Ukraine in the Poltava region

Shevchenko str. 115-30, 36039 Poltava, Ukraine

tel: +380662369670

e-mail: d.a.shkurupiy@gmail.com

Received: 15.10.2017

Accepted: 05.04.2018

Table I. Condition of protein metabolism in newborns in conditions of intensive care of relatively healthy newborns

Indicator

Main group

(n = 143)

Comparison group

(n = 30)

р

Total protein, g/l

58,38±0,78

64,89±1,86

р < 0,05

Albumin, g/l

30,97±0,9

35,5±0,91

р < 0,05

g-globulins, g/l

8,87±0,39

14,91±0,47

р < 0,05

Ig A, g/l

1,68±0,1

1,9±0,08

р < 0,05

Ig M, g/l

1,16±0,05

1,44±0,04

р < 0,05

Ig G, g/l

6,74±0,2

10,64±1,07

р < 0,05

Table II. Condition of protein metabolism in newborns under intensive care depending on the type of enteral formula and relatively healthy newborns

Indicator

Main group

(n = 143)

Comparison group

(n = 30)

р

semi-elemental hydrolyzates

(n = 83)

adapted formulas
(n = 60)

Total protein, g/l

60,23±0,92

59,32±1,42

64,89±1,86

р1 < 0,05

р2 > 0,05

р3 > 0,05

Albumin, g/l

35,68±0,46

33,04±0,72

35,5±0,91

р1 < 0,05

р2 > 0,05

gglobulins, g/l

10,52±0,22

8,59±0,32

14,91±0,47

р1 < 0,05

р2 < 0,05

р3 < 0,05

Ig A, g/l

1,87±0,1

1,31±0,11

1,9±0,08

р1 < 0,05

р2 > 0,05

р3 < 0,05

Ig M, g/l

1,17±0,04

1,14±0,05

1,44±0,04

р1 > 0,05

р2 < 0,05

р3 < 0,05

Ig G, g/l

7,47±0,18

6,14±0,56

10,64±1,07

р1 < 0,05

р2 < 0,05

р3 < 0,05

Notes:

p1 – probability of error when comparing patients of the main group depending on the type of enteral formula;

p2 – probability of error when comparing patients of the main group receiving semi-elemental hydrolyzates relative to the comparison group;

p3 – probability of error when comparing patients in the main group receiving adapted formulas relative to the comparison group.