Document Type : Original Article
Authors
1 Department of Clinical Pharmacy, College of Pharmacy, Mazandaran University of Medical Sciences
2 Department of pediatrics, School of Medicine,Mazandaran University of Medical Sciences
3 Department of medical technology, School of Medicine, Mazandaran University of Medical Sciences
4 Mazandaran University of Medical Sciences
Abstract
Keywords
Introduction
Malnutrition, as a common problem at hospital admission, tends to increase during hospital stay. In Europe and North America, 40-50% of hospitalized patients may be at risk of malnutrition. The incidence of malnutrition in critically ill children varies between 25% and 70%, depending on the examined series (1, 2-6). According to a previous study, 15–20% of children, admitted to neonatal intensive care units (NICUs), were acutely or chronically malnourished (7).
After birth, preterm infants lose weight and take variable periods to regain birth weight. The postnatal development of premature infants is critically dependent on an adequate nutritional
intake that mimics a similar gestational stage to which the fetus would be exposed if still in the uterus (8). Deficient protein or amino acid administration over an extended period may cause significant growth delays or morbidity in very low birth weight (VLBW) infants (9).
More aggressive parenteral nutrition (PN) with higher energy and protein intake might lead to reduced energy and protein deficit. However, early total PN is limited by glucose and lipid intolerance as well as by concerns regarding amino acid metabolism. Abnormal neurodevelopment in preterm infants has been associated with inadequate nutrition during the early postnatal period (10, 11).
Table1. Demographic characteristic of neonates
|
Demographic characteristics |
Variables |
Male infants (mean±SD) |
Female infants (mean±SD) |
|
Sex (%) |
49 |
51 |
|
|
At birth |
Weight (g) |
2568±745 |
2215±969 |
|
Height (cm) |
45.8±4.2 |
43.4±5.9 |
|
|
Head circumference (cm) |
32.2±3.1 |
30.7±3.5 |
|
|
at NICU admission time |
Weight (g) |
2535±768 |
2200±943 |
|
Height (cm) |
46.3±4.2 |
43.9±6.1 |
|
|
Head circumference (cm) |
32.7±3.2 |
30.9±3.7 |
|
|
Age (day) |
4.8±8.5 |
5.3±2.8 |
Table 2. Anthropometric parameter changes in neonates during NICU stay
|
Variables |
Gestational age (w) |
|
At birth |
At admission |
Day 5 |
Day 10 |
Day 15 |
Day 20 |
|
Weight |
≤30 |
Observed |
1357±499 |
1389±478 |
1354±484 |
1184±142* |
1173±132* |
1230±71* |
|
Standard |
1330 |
1380 |
1500 |
1840 |
2000 |
2140 |
||
|
31-34 |
Observed |
1780±616 |
1784±614 |
1748±613 |
17.3±707* |
1120±367* |
-- |
|
|
Standard |
1850 |
1920 |
2060 |
2250 |
2410 |
-- |
||
|
35-37 |
Observed |
2443±541 |
2415±540 |
2360±577 |
2660±377* |
2647±208* |
2606±172* |
|
|
Standard |
2650 |
2730 |
2850 |
3000 |
3130 |
3250 |
||
|
≥38 |
Observed |
3222±525 |
3219±576 |
3188±581 |
3081±518* |
3027±553* |
2943±445* |
|
|
Standard |
3370 |
3400 |
3500 |
3600 |
3720 |
3850 |
||
|
Height |
≤30 |
Observed |
39±4 |
39±4 |
39±4 |
38.3±5 |
37.5±3* |
37±2* |
|
Standard |
39 |
39.5 |
40.5 |
42.9 |
43.7 |
44.5 |
||
|
31-34 |
Observed |
42.5±6.4 |
42.6±6.2 |
42.7±6.2 |
40±5.4* |
36.5±0.7* |
-- |
|
|
Standard |
42.8 |
43 |
44 |
44.8 |
45.1 |
-- |
||
|
35-37 |
Observed |
45.1±3.1 |
45.4±3.1 |
45.4±3.1 |
47.4±3.7 |
46±3.9* |
45.5±4.4* |
|
|
Standard |
46.5 |
46.7 |
47.4 |
48.1 |
48.7 |
49.3 |
||
|
≥38 |
Observed |
48±3 |
49±3.5 |
49±3.5 |
48±4 |
49±4 |
44±3.5* |
|
|
Standard |
50 |
50 |
50.5 |
51 |
51.8 |
52 |
||
|
Head circumference |
≤30 |
Observed |
27±3 |
27±3 |
27±3 |
27.3±2 |
27.5±2* |
28±1* |
|
Standard |
26.5 |
27 |
28.3 |
29.8 |
30.4 |
31 |
||
|
31-34 |
Observed |
294±21 |
29.4±2.3 |
29.5±2.4 |
29.2±2.7 |
28.8±3.2* |
-- |
|
|
Standard |
29 |
29.2 |
29.8 |
30 |
30.4 |
-- |
||
|
35-37 |
Observed |
32.4±1.6 |
32.5±1.5 |
32.5±1.5 |
33.1±1.8 |
33.2±205 |
33±3.1 |
|
|
Standard |
32.5 |
32.6 |
33 |
33.5 |
33.9 |
34.3 |
||
|
≥38 |
Observed |
34±2 |
35±2.5 |
35±2.5 |
34±2.5 |
34±3 |
34±2.5 |
|
|
Standard |
34.5 |
34.5 |
35 |
35.2 |
35.5 |
35.8 |
* These variables had meaningful differences with normal values.
Furthermore, in the short run, suboptimal nutrition is associated with adverse outcomes including increased susceptibility to infections, greater need for mechanical ventilation, and development of chronic lung diseases (12). Recommended intakes are commonly interrupted for clinical reasons, and VLBW infants, during their initial hospital stay, develop major calorie deficits, which are not compensated for by the time of hospital discharge (8).
It is estimated that 1% of endogenous proteins may be lost each day if the preterm infant is provided with only glucose after birth (13, 14). Therefore, there is an urgent need for optimal nutrition at the time of birth. Moreover, the incidence rates of head circumference and length < 10th percentile have been reported to be 34% and 16% at discharge, respectively (15). Dusick et al. reported that 97% and 40% of VLBW infants experience growth failure at 36 weeks and 18-22 months post-conceptual age, respectively (13).
A number of national committees have recommended a daily energy intake of 110-130 kcal/kg/day for healthy premature infants to allow a growth rate similar to that of intrauterine growth rate (16). There are diverse practices with regard to neonatal PN in the United Kingdom. The current neonatal PN practice entailsa significant calorie and protein deficit during the early postnatallife and warrants further review. The purpose of this study was to evaluate the nutritional status of infants in the NICU of a teaching hospital.
Material and Method
We conducted this prospective observational study to determine the nutritional status of critically ill neonates by evaluating their anthropometric and biochemical parameters in a tertiary NICU. Overall, 100 consecutive neonates, admitted to NICU, were evaluated.
The neonates’ demographic characteristics (age, weight, and height), energy source (dextrose and lipids), and protein level on the 1st, 5th, 10th, 15th, and 20th days of admission were recorded, and blood samples were obtained to measure
Table 3. Serum albumin, prealbumin, and parenteral calorie intake in neonates during NICU stay
|
Variables |
|
Day 1 |
Day 5 |
Day 10 |
Day 15 |
Day 20 |
|
Preterm |
Albumin |
4.0±1.8 |
3.9±1.5 |
3.6±1.4 |
3.3±0.8* |
2.8±0.5* |
|
Prealbumin |
10.5±4.8* |
9.6±3.7* |
10.2±3.4* |
9.8±3.3* |
8.5±3.1* |
|
|
Term |
Albumin |
4.0±1.2 |
3.6±1.3 |
4.0±1.9 |
3.5±1.2 |
3.4±1 |
|
Prealbumin |
10.3±3.4* |
11±4.3 |
13.2±8 |
9.6±3.9* |
9.5±4.9* |
|
|
Calorie (Cal/kg) |
Received |
28.4* |
31.2* |
30.5* |
36.5* |
34* |
|
Required |
110 |
110 |
105 |
105 |
110 |
* These variables had meaningful differences with normal values.
Table 4. The relationship between NPO duration and patients’ outcomes
|
NPO duration |
Outcomes |
Patients (No.) |
|
|
Discharge |
Death |
|
|
|
36 |
6 |
42 |
|
|
4-6 days |
35 |
2 |
37 |
|
7-9 days |
8 |
9 |
17 |
|
>10 days |
2 |
2 |
4 |
|
Total |
81 |
19 |
100 |
|
P-value=0.008 |
|
|
|
albumin and prealbumin. The calorie and protein levels were calculated for all preterm and term neonates and separately compared with the recommended mean values. The patients were classified as severely, moderately, and mildly malnourished, based on serum prealbumin and albumin levels.
Data were analyzed by SPSS version 16, and P-value ≤ 0.05 was considered statistically significant.
Results
Table 1 shows the characteristics of 100 enrolled neonates at birth and admission time. The subjects were followed-up on the 1st, 5th, 10th, 15th, and 20th days of admission. Changes in anthropometric parameters are shown in Table 2. Table 3 shows the patients’ biochemical parameters (albumin and prealbumin levels) and calorie intake during the NICU stay. Moreover, the relationships between patients’ outcomes and ‘no oral intake’ (NPO) duration, serum albumin level, and prealbumin concentration are reported in Tables 4-6.
Discussion
The aim of this study was to investigate the nutritional status of neonates at the NICU of a
Table 5. The relationship between serum albumin and patients’ outcomes
|
Albumin level at the time of admission (g/dL) |
Outcomes |
Patients (No.) |
|
|
Discharge N (%) |
Death N (%) |
||
|
Severe malnutrition (<2) |
3 (50) |
3 (50) |
6 |
|
Moderate malnutrition (2-2.5) |
12 (66.7) |
6 (33.3) |
18 |
|
Mild malnutrition (2.5-3) |
16 (76.2) |
5 (23.8) |
21 |
|
Normal (3-4.5) |
22 (88) |
3 (12) |
25 |
|
Upper normal (>4.5) |
17 (94.4) |
1 (5.6) |
18 |
|
Total |
70 (79.5) |
18 (20.5) |
88 |
|
P-value=0.004 |
|
|
|
teaching hospital. Our data revealed that growth in terms of weight, height, and head circumference was not adequate in patients, particularly on day 10 of admission and later. Based on neonatal weight, the mean daily parenteral calorie intake was ≤ 30% lower than the daily requirements.
Serum prealbumin concentration was meaningfully different from the normal value since the first day until the 20th day of hospitalization in preterm and the majority of term infants, whereas serum albumin level was lower than the normal value in preterm infants only on days 15 and 20. There was a positive relationship between NPO duration and patients’ mortality. Moreover, serum albumin had a significant negative relationship with mortality rate, whereas prealbumin level was not significantly correlated with patient outcomes.
Extrauterine growth restriction remains a common and serious problem in premature neonates, especially small, immature, and critically ill infants (15). The ultimate goal of neonatal nutrition is to replicate in utero growth patterns. Fetal growth is at a minimum rate of 15 g/kg/day during the mid-trimester, decreasing to 10 g/kg/day at full term (17). The American Academy of Pediatrics recommends that the postnatal growth of preterm infants in terms of both anthropometric indices and body composition should be the same as the normal fetus with the same gestational age (18).
The risk of developing malnutrition during the infant’s stay at NICU can only be minimized by standardized nutritional assessment upon admission, which should enable identifying children at higher risk and optimize their nutritional support (7). The major nutritional components for preterm infants include
Table 6. The relationship between serum prealbumin and patients’ outcomes
|
Prealbumin level at the time of admission (mg/dL) |
Outcomes |
Patients (No.) |
|
|
Discharge No. (%) |
Death No. (%) |
||
|
Severe malnutrition (<5) |
1 (50) |
1 (50) |
2 |
|
Moderate malnutrition (5-10.5) |
51 (81) |
12 (19) |
63 |
|
Mild malnutrition (10.6-15.9) |
20 (80) |
5 (20) |
25 |
|
Normal (16-40) |
9 (100) |
0 (0) |
9 |
|
Total |
81 (81.8) |
18 (18.2) |
99 |
|
P-value=0.19 |
|
|
|
appropriate amounts of essential nutrients (mainly glucose, lipids, and amino acids), received via parenteral routes.
Carbohydrates are the main energy source for neonates, receiving PN in form of glucose. Glucose synthetic rates in preterm infants are much higher at 6-8 mg/kg/min, compared to term infants, who synthesize glucose with a rate of 3-5 mg/kg/min. Maintaining normal glucose concentrations that match those of a normally growing fetus (> 50 mg/dl) is important for neurodevelopment (19). In the present study, although dextrose was the main source of energy, most of the neonates did not receive adequate daily calories, and only 30% or less met the daily needs.
The ideal energy ratio provides 65% of energy as carbohydrates and 35% as lipids. Most infants require 100-120 cal/kg/day for adequate growth, whereas some neonates need up to 160-180 cal/kg/day (e.g., infants with bronchopulmonary dysplasia). In fact, the primary goal is to provide energy and nutrients in sufficient quantities to allow normal growth and development (20).
Lipid is a good source of energy, given its high energy density; in fact, 1 gram of fat provides 9 kcal or 37.8 Joules of energy, and 1 gram of carbohydrate and protein provide about 4 kcal or 16.8 Joules, each. Essential fatty acid deficiency may develop within the first 72 hours of life and can be avoided by giving at least 0.5-1 g/kg/day of intravenous lipids. Suboptimal nutrition during sensitive stages in early brain development may have long-term effects on cognitive function (21). Early lipid administration by day two of life is safe and well tolerated (22).
Proteins are essential for normal growth and development. Growth of lean body mass is particularly dependent on protein intake in organs such as the brain. As a number of studies have reported, failure to provide dietary proteins of at least 1 g/kg/day would result in protein breakdown, presenting as negative nitrogen balance (9, 23, 24). Protein is a building block for new tissues rather than an ideal source of energy. Therefore, even if energy intake from proteins is included in calculations of total energy intake, not all protein-derived calories are available for energy expenditure.
Protein administration should be started on the first day of life or as soon as the fluid and electrolyte requirements have been met. In fact, a non-protein-to-protein calorie ratio of at least 25-30:1 should be maintained. Term infants need 1.8-2.2 g/kg/day along with adequate non-protein energy for growth, whereas preterm VLBW infants need 3-3.5 g/kg/day, along with adequate non-protein energy for growth; usually, providing more than 4 g/kg/day of protein is not advisable (25, 26)
In consistence with our findings, Grover et al. reported that in only 26 NICUs (54%) in England (from 52 NICUs), PN was initiated on day 1, and full PN was achieved by the median duration of 6 days. Twelveunits (25%) achieved full PN only by day 7 or later; maximummedian amino acid was 2.9 g/kg/day. Only 13 units (27%) prescribed3 g/kg/day, and 2 prescribed more than 3.5 g/kg/day. Nineteen units(39%) initiated lipids on day 1, 11 units (23%) delayedlipids until day 3, and 2 units delayed lipids until day 4.In comparison with the recommended intake of calories and aminoacids, the current median prescription would result in a cumulative deficitof 420 kcal/kg and 11.9 g/kg over the first 10 days, respectively (27).
Albumin is a parameter that is widely used in nutritional evaluation due to its high specificity. However, it has a low sensitivity as a nutritional marker, given its long plasma half-life (20 days); therefore, it is not a good parameter for monitoring nutritional status, due to its low sensitivity to acute changes (28). Other body proteins with shorter half-lives are better alternatives for the evaluation of protein status in critically ill patients. Prealbumin, with a short half-life of two days and limited distribution, is very sensitive and specific to changes in the nutritional status. Variations in prealbumin concentration can be observed in less than 7 days after diet changes.
Some studies have reported a good correlation between prealbumin level and nitrogen balance (29-32). Prealbumin is a useful parameter for monitoring the nutritional status, re-nutrition, and changes in nutritional patterns in seriously ill patients; in fact, it is the only valid parameter for the evaluation of nutritional status in patients with renal failure (28). In the present research, in agreement with the results of previously conducted studies, prealbumin was a better biochemical parameter for evaluating nutritional status, compared to albumin, although patients did not receive the recommended daily calorie and protein requirements.
Delgado et al. reported that during standardized metabolic support, serum albumin did not significantly change, but the mean value of prealbumin increased significantly from the 1st to the 10th day (33). In consistence with previous studies (34-38), we also found that patients with lower serum albumin level had a significantly higher mortality rate, whereas there was no significant relationship between low prealbumin level and mortality rate.
In adult patients, hypoalbuminemia was shown to be a strong independent predictor of poor outcomes, and each 1 g/dL decline in albumin significantly elevated the risk of mortality and morbidity and increased the length of hospital stay (34). Several pediatric studies have suggested an association between low serum albumin and adverse clinical sequelae such as necrotizing enterocolitis, poor surgical outcomes, prolonged length of NICU stay, and mortality (35-38). Unfortunately, in these studies, amino acid and intralipid formulae for neonates were not available to be prescribed as calorie and protein sources.
Conclusion
Similar to many previous studies, the evaluated infants did not receive their whole daily calorie and protein requirements. Based on numerous studies, timely and adequate administration of suitable calorie sources (dextrose and lipids) and amino acids is recommended. Prealbumin was a better biochemical parameter, compared to albumin for evaluating patients’ short-term nutritional status, particularly in critically ill patients. This study was funded by Mazandaran University of Medical Sciences.
)