Metabolism of carbohydrates in low birth weight newborns at different types of feeding

Yuri V Chernenkov; Larisa G Bochkova; Irina I Kadymova; Anton R Kiselev

doi:10.4103/jcn.jcn_121_21

ORIGINAL ARTICLE

Year : 2022 | Volume : 11 | Issue : 2 | Page : 90-96

Metabolism of carbohydrates in low birth weight newborns at different types of feeding

Yuri V Chernenkov¹, Larisa G Bochkova¹, Irina I Kadymova¹, Anton R Kiselev²
¹ Saratov State Medical University, Saratov, Russia
² National Medical Research Center for Therapy and Preventive Medicine, Moscow, Russia

Date of Submission	06-Oct-2021
Date of Decision	07-Jan-2022
Date of Acceptance	17-Jan-2022
Date of Web Publication	20-Apr-2022

Correspondence Address:
Yuri V Chernenkov
Department of Pediatrics and Neonatology, Saratov State Medical University, 112, Bolshaya Kazachya Str., Saratov, 41001
Russia

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jcn.jcn_121_21

Abstract

Context: Preterm infants need plenty of energy and nutrients supplied by carbohydrates, in particular glucose. Aims: The aim was to study the associations of the carbohydrate content in blood and in feces with intrauterine growth retardation (IUGR) and different types of feeding in low birth weight (LBW) preterm infants. Subjects and Methods: This prospective study included 173 preterm infants with LBW, including those with IUGR. The dynamic monitoring of carbohydrates indicators in blood and feces, as well as the analysis of these parameters depending on the birth weight and type of feeding, have been performed. Results: Infants with LBW exhibited a higher excretion of carbohydrates with feces in preterm infants who received breast milk by the end of the neonatal period. The low level of glycemia in newborns during breastfeeding is explained by the fact that with this type of feeding the use of glucose is more intensive. Conclusions: LBW preterm infants had an increased level of carbohydrates in feces, which implied an enzymatic insufficiency that has persisted throughout the observation period. However, the level of excretion depended, first of all, on the type of feeding of the preterm infants. The level of hypoglycemia was significantly associated with the occurrence of IUGR.

Keywords: Blood glucose, carbohydrates in feces, carbohydrates metabolism, low birth weight, newborns

How to cite this article:
Chernenkov YV, Bochkova LG, Kadymova II, Kiselev AR. Metabolism of carbohydrates in low birth weight newborns at different types of feeding. J Clin Neonatol 2022;11:90-6

How to cite this URL:
Chernenkov YV, Bochkova LG, Kadymova II, Kiselev AR. Metabolism of carbohydrates in low birth weight newborns at different types of feeding. J Clin Neonatol [serial online] 2022 [cited 2023 Mar 21];11:90-6. Available from: https://www.jcnonweb.com/text.asp?2022/11/2/90/343415

Introduction

In accordance with the WHO recommendation, newborns weighing under 2500 g are considered low birth weight (LBW) newborns, regardless of the causes and duration of pregnancy that caused this condition.^[1],[2] They are further classified into very LBW newborns (VLBW; 1000‒1499 g) and extremely LBW newborns (ELBW; 500‒999 g).^[3] The reasons for LBW are prematurity, intrauterine growth retardation (IUGR), and the combination of both.^[4]

Preterm infants need much energy and nutrients supplied by carbohydrates^[5] – in particular, by glucose. The viability of preterm infants largely depends on the metabolism of glucose,^[6],[7] and is directly related to adequate enteral nutrition.^{[8],[9],[10],[11],[12]} The tendency of preterm infants to fluctuations in the level of glycemia is caused by the problems of their neonatal adaptation. At the same time, the high energy requirement and low glycogen content in preterm infants create the risk of hypoglycemia. Intrauterine disorders of placental blood flow, such as acute hypoxia in maternal eclampsia and placental abruption, along with perinatal asphyxia often result in hyperglycemia, contributing to the induction of gluconeogenesis.^[9] Therefore, the assessment of carbohydrate tolerance in children with LBW is a prerequisite for the correction of energy metabolism. It is necessary to consider not only the gestational age but also the original trophic disorders, as well as the type of feeding. When analyzing the feeding of premature newborns and the associated level of carbohydrate excretion with feces, some authors point out a high level of carbohydrate excretion with feces that does not always correlate with the clinical symptoms of lactase deficiency.^[13]

When the activity of lactase typical for preterm infants is low, unhydrolyzed lactose inevitably forms in the small intestine; it is later fermented by intestinal flora, causing functional lactase deficiency.^{[14],[15],[16]} This is an issue of transient lactase deficiency in preterm infants, which indicates the need for further research aimed at studying the clinical and metabolic features of carbohydrate homeostasis in newborns.^[7]

The aim was to study the characteristics of the carbohydrate content in blood and feces of LBW preterm infants with or without IUGR under different types of feeding.

Subjects and Methods

Subjects

This prospective study included 173 LBW preterm infants with birth weights of 500‒2499 g and gestational age of 23–38 weeks, including infants with IUGR. The exclusion criteria were preterm infants with surgical pathology and infectious diseases.

According to their birth weights,^[3] all newborns were divided into six groups:

42 ELBW preterm infants (500‒999 grams) without IUGR
17 ELBW preterm infants with IUGR
30 VLBW preterm infants (1000‒1499 g) without IUGR
38 VLBW preterm infants with IUGR
30 moderately LBW (MLBW) preterm infants (1500‒2499 g) without IUGR
16 MLBW preterm infants with IUGR.

The data on gestational age and postconceptual age of preterm infants enrolled in this study are presented in [Table 1].

Table 1: Gestational age and perinatal histories in feces in studied low birth weight newborns

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The reason for our classification of preterm infants into weight categories was the occurrence of IUGR in some of the examined newborns. In this case, the comparison groups were newborns with birth weights from 1500 to 2499 g.

The age of mothers ranged from 17 to 42 years. They had some extragenital diseases and pregnancy complications, such as hypertension, diseases of the digestive system, urinary system, placental abruption, preeclampsia and eclampsia, threatened miscarriage, and utero-placental insufficiency [Table 1].

Nutrition of newborns

All infants with ELBW received parenteral nutrition combined with minimal trophic nutrition since the 1^st day of their lives. Due to the issue of stabilizing the vital functions, enteral feeding with a special infant formula for ELBW preterm infants became possible mainly only on day 8 of their lives.

VLBW preterm infants were fed enterally from days 5 to 6 of their lives. MLBW infants were fed enterally from the 1^st day of life. The newborns with VLBW and LBW were fed enterally with specialized infant formulas or breast milk.

Study design

The design of this study was approved by the Ethics Committee of Saratov State Medical University (Saratov, Russia). All procedures performed in the studies involving human participants were in accordance with the ethical standards of the Institutional Research Committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Clinical examination of patients included an objective examination; evaluation of the maturity of newborns in terms of their gestational age and anthropometric parameters, mass dynamics, body length, and head circumference; as well as the condition of preterm infants and clinical syndromes during the neonatal period. Physical development was assessed by the method of Fenton.^[17]

Every 10 days, the glucose level in blood of all preterm infants was determined via the glucose oxidase method using the “Photoglucose” kit (Impact LLC, Russia). The principle of this method is based on the oxidation of β-D-glucose by atmospheric oxygen via the catalytic action of glucose oxidase. The level of carbohydrates in feces was studied in preterm infant groups on days 10 and 25 of life using Benedict's method.

Statistical analysis

For continuous variables, descriptive statistics are reported as the median and interquartile ranges (LQ, UQ) for nonnormal distribution, and as the mean (M) and standard deviation for normal distribution. We applied the Shapiro–Wilk test to check whether the data were approximately normally distributed. Binary variables are presented as frequencies and percentages, n (%).

The Mann–Whitney test was used to compare the continuous variables between groups. We used gamma correlation to evaluate the strength of pair association between ordinal variable and continuous variable. To compare the variables within one patient group, we used the Wilcoxon test. The point-biserial correlation was used to measure the strength of pair association between the dichotomous variable and continuous variable.

A receiver operating characteristic (ROC) analysis and the Youden index were used to identify effective cutoff points for separating the newborns of different groups in terms of the studied continuous carbohydrates metabolism parameters (blood glucose and carbohydrate excretion rates).

The obtained estimations were considered statistically significant at P < 0.05.

Results

The analysis of the glycemia in preterm infants with and without IUGR showed that lower blood glucose values were observed in ELBW infants with IUGR at days 10 and 20 of their lives, and in VLBW/MLBW preterm infants at only day 20 of their lives, compared with infants of similar weight without IUGR [Table 2].

Table 2: Blood glucose level and carbohydrate level in feces in studied low birth weight newborns

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The study of carbohydrate level in feces in all preterm infants of early neonatal age demonstrated higher than normally acceptable values. The analysis of carbohydrates in feces of infants with and without IUGR showed statistically significant differences only in ELBW preterm infants on both days 10 and 20 of their lives [Table 2]. ELBW preterm infants with IUGR had lower content of carbohydrates in feces, compared with ELBW preterm infants without IUGR [Table 2].

Among newborns of similar weight with or without IUGR, we did not find any significant differences in the studied carbohydrates metabolism parameters (blood glucose and carbohydrate in feces) [Table 2]. The only exception was a consistent increase in the level of carbohydrates in feces on day 20 day of their lives with an increase of their birth weight along the following gradient: ELBW preterm infants → VLBW preterm infants → MLBW preterm infants [Table 2].

When comparing preterm infants receiving the formula feeding with preterm infants receiving native breastfeeding, statistically higher values of blood glucose level were demonstrated in the former by day 20 of their lives, with no significant differences on day 10 [Table 3].

Table 3: Blood glucose level (mmol/L) and carbohydrate level in feces (mg%) in newborns under formula feeding or native breast milk feeding

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Levels of carbohydrates in feces of preterm infants as early as on day 10 of their lives were significantly lower in those with formula feeding [Table 3]. Subsequently, by day 20, in preterm infants with formula feeding, the carbohydrate content decreased even more, whereas in breastfed preterm infants, this indicator slightly increased [Table 3], which ultimately enlarged the differences between these subgroups on day 10 of their lives.

We studied the correlation between carbohydrates metabolism parameters (blood glucose and carbohydrates in feces) versus clinical characteristics of newborns (birth weight, IUGR, and types of feeding) [Table 4]. A statistically significant relationship has been found between the type of feeding and excretion of carbohydrates with feces in early and late neonatal age (10 and 20 days old), which was significantly enhanced by the 20^th day of life (r = −0.81, P < 0.001). The level of glycemia was significantly associated (r = 0.25, P = 0.001) with the type of food only for the 20^th day of life.

Table 4: Correlation analysis results between carbohydrates metabolism parameters (blood glucose and carbohydrate level in feces) versus clinical characteristics of newborns (birth weight, intrauterine growth retardation, and types of feeding)

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The weight of preterm infants at birth correlated statistically significantly exclusively with the level of carbohydrates in feces on day 20 of their lives [Table 4].

It is noteworthy that the level of glycemia throughout the observation period correlated significantly with the occurrence of IUGR, regardless of the feeding type or body weight at birth [Table 4].

We have performed the ROC analysis to identify the effective cutoff points for the studied continuous carbohydrates metabolism parameters with the goal of classifying preterm infants into categories in terms of feeding type, body weight at birth, and occurrence of IUGR. The results of the ROC analysis are presented in [Table 5]. Overall, they are consistent with the results of the correlation analysis.

Table 5: Receiver operating characteristic analysis results of continuous carbohydrates metabolism parameters (blood glucose and carbohydrate level in feces) versus clinical characteristics of newborns (birth weight, intrauterine growth retardation, and types of feeding)

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Discussion

The results of our study make it possible to assume that the body weight category of a newborn does not determine the indicators of carbohydrates metabolism (blood glucose and carbohydrates in feces). These metabolic parameters can be determined by the type of preterm infant feeding and the occurrence of IUGR. However, the level of glycemia at all times of observation in our study was primarily determined by the presence/absence of IUGR, while excretion of carbohydrates with feces was chiefly based on the type of feeding. The revealed weak association between the body weight of the preterm infant at birth and carbohydrates metabolism parameters were explained by the fact that the birth weight affected, to some extent, the choice of the preterm infant feeding type. The logical framework of an influence of the studied indicators sensu our hypothesis is presented in [Figure 1].

Figure 1: The framework of directions of association between carbohydrates metabolism parameters (blood glucose and carbohydrate excretion rates) and clinical characteristics of newborns (birth weight, intrauterine growth retardation, and types of feeding). carbohydrate excretion rates. Note #1 Imitation of correlation (confounder is the type of feeding)

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In all studied preterm infants (ELBW formula-fed infants and VLBW/MLBW infants who received both native breast milk and a formula for preterm infants), the blood glucose level was within the limits of the reference values. This demonstrated a sufficient homogeneity of the preterm infant groups in terms of carbohydrates metabolism. Various authors previously stated a fairly wide variability in the level of glycemia in LBW newborns (from hypoglycemia to hyperglycemia).^{[18],[19],[20]}

By the end of the neonatal period, significantly lower blood glucose values were still registered predominantly in infants with IUGR (P < 0.001). At the same time, in the breastfed preterm infants, compared with those fed with a special formula, blood glucose content was only slightly lower. This result can be explained by slower utilization of carbohydrates in formula-fed infants and higher blood glucose values in this category of infants.

An analysis of carbohydrate levels in blood and feces of preterm infants with LBW demonstrated a higher excretion of carbohydrates with feces in the newborns breastfed by the end of the neonatal period. The low level of glycemia in breastfed preterm infants is explained by the fact that under this type of feeding, the glucose utilization is more intensive, which is due to genetic predisposition of their enzymatic systems to the consumption of breast milk and its components. Similar results were obtained in many other studies.^{[7],[12],[21]} These data were regarded as a manifestation of transient disaccharidase insufficiency failure in the immaturity of digestive tract.

Nonetheless, such studies did not take into consideration the weight of infants at birth and the type of feeding. The decrease in excretion of carbohydrates with feces that occurred in formula-fed infants can be explained by both the reduced content of lactose in nutrient formulas and the faster maturation of enzymes in preterm infants on formula feeding.

The results of ROC analysis showed that formula-fed ELBW newborns were characterized by the level of carbohydrate excretion rates ≤0.65 mg% [Table 5]. Of ELBW/VLBW preterm infants, those with IUGR who were breastfed, had a glycemic level ≤3.1–3.8 mmol/L [Table 5]. We believe that these cutoff points are of interest for understanding the physiology of carbohydrates metabolism in newborns with different weights at birth, the occurrence (or absence) of IUGR, and different types of feeding. Such quantitative estimates could be useful in mathematical modeling of carbohydrates metabolism in newborns.

Contemporary methods of managing glucose metabolism (including feeding types) in LBW preterm infants can determine the dynamics of parameters of their subsequent physical development. Some authors have reported significant body weight differences between the contemporary Russian children 1–14 years of age and similar children in the end of the previous century.^[22]

Conclusions

LBW preterm infants demonstrated an increased level of carbohydrates in feces, which implied an enzymatic insufficiency that persisted throughout the entire observation period. However, the level of excretion depended, first of all, on the type of feeding of preterm infants: Breast milk promoted an increase in the carbohydrate content of feces. The level of hypoglycemia was significantly associated with the occurrence of IUGR.

Limitations

It should be pointed out that we were not able to identify the features of the carbohydrate metabolism in ELBW preterm infants with or without IUGR. This was caused by the late onset of enteral feeding due to the extreme immaturity of these infants. From birth, they have been receiving only parenteral nutrition in combination with trophic nutrition in a volume of 1–5 mL per day with a gradual increase in the milk dose, which could not seriously affect the metabolism of carbohydrates. In addition, sample sizes of some groups, such as ELBW preterm infants with IUGR, were very small due to the chosen exclusion criteria, such as the presence of infections.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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