|Year : 2020 | Volume
| Issue : 1 | Page : 127-131
Prevalence of glucose level abnormalities in neonatal sepsis and its association with mortality
Dalia M Ellahony1, Muhammad S El-Mekkawy1, Abd El Hameed R A. Issa2
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Benha, Egypt
2 Department of Pediatrics, Ministry of Health, Benha, Egypt
|Date of Submission||09-Jul-2018|
|Date of Decision||05-Aug-2018|
|Date of Acceptance||06-Aug-2018|
|Date of Web Publication||25-Mar-2020|
Abd El Hameed R A. Issa
387 Canal El Suez, El Shatby, Bab Sharq, Alexandria 21111
Source of Support: None, Conflict of Interest: None
To determine the prevalence of plasma glucose abnormalities among infants with neonatal sepsis and their association with mortality and morbidity.
Plasma glucose abnormalities were previously noted in neonatal sepsis, but data in full-term neonates is limited and the association with mortality and morbidity is not established.
Patients and methods
This was a prospective observational study including 114 full-term neonates with culture-proven and probable sepsis. Plasma glucose level was measured within 2 h of neonatal intensive care unit admission and the patients were monitored till discharge or mortality. The patients were divided into three groups according to their plasma glucose level into hyperglycemic, hypoglycemic, and normoglycemic subgroups.
Of the patients, 8.7% were hyperglycaemic; 8.7% were hypoglycemic, and 82.6% were normoglycemic. Mortality in the hypoglycemic, hyperglycemic, and normoglycemic subgroups were 20, 20, and 17%, respectively (P = 0.8). There was no significant difference in the length of hospital stay according to the glycemic status (P = 0.3). In addition, the glycemic status was not associated with the need for mechanical ventilation (P = 0.99).
Plasma glucose abnormalities are not uncommon among full-term neonates with sepsis. However, these abnormalities are not associated with morbidity or mortality. Larger studies are needed to confirm these findings.
Keywords: hyperglycemia, hypoglycemia, mortality, neonatal sepsis, plasma glucose
|How to cite this article:|
Ellahony DM, El-Mekkawy MS, A. Issa AE. Prevalence of glucose level abnormalities in neonatal sepsis and its association with mortality. Menoufia Med J 2020;33:127-31
|How to cite this URL:|
Ellahony DM, El-Mekkawy MS, A. Issa AE. Prevalence of glucose level abnormalities in neonatal sepsis and its association with mortality. Menoufia Med J [serial online] 2020 [cited 2020 Mar 30];33:127-31. Available from: http://www.mmj.eg.net/text.asp?2020/33/1/127/281274
| Introduction|| |
Neonatal sepsis is an important cause of neonatal morbidity and mortality, and it is an major ongoing global public health challenge. The perinatal period is hazardous because of multiple opportunities for exposures to virulent organisms. There are multiple sites of exposure including the uterus, the birth canal, the neonatal care unit, invasive procedures and devices, health-care providers family and visitors, and the community. In addition to these sites of exposure and different modes of infection transmission, neonates are relatively immunocompromised. The innate immune function of premature infants is impaired predisposing them to invasive infections. The fetal immune response begins at about 24 weeks of age and development occurs until term; therefore, premature neonates do not benefit from complete immune system development, making them more susceptible to infection with organisms that term infants may be able to suppress. Neonatal sepsis is divided – according to the onset of age – into early-onset sepsis (EOS) and late-onset sepsis (LOS). EOS reflects transplacental or, more frequently, ascending infections from the maternal genital tract, whereas LOS is associated with the postnatal community environment or nosocomial, with the peak incidence reported to be between the 10th and 22nd day of life. Since the early 1980 s, a general reduction in EOS was observed, probably due to advances in obstetric care and the use of prophylactic intrapartum antibiotics to prevent infections caused by group B Streptococcus spp. However, the incidence of LOS has increased in parallel with the improved survival of premature infants, especially in those with very low birth weight, indicating the role of hospitalization and advanced medical devices in the pathogenesis of neonatal LOS. Neonatal sepsis is a systemic infection occurring in infants in the first 28 days of life and is a major cause of morbidity and mortality in newborns. According to the International Pediatric Consensus Conference of 2001, the definition of neonatal sepsis was a systemic inflammatory response syndrome in the presence of or as a result of suspected or proven infection with or without the accompanying bacteremia, documented by a positive blood culture in the first 28 days of life. Sepsis encompasses various systemic infections of the new born such as septicemia, meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections. Newborns, especially preterms, are more susceptible to infections than older children. Recent years have witnessed a significant drop in childhood mortality all over the world. However, neonatal mortality has decreased at a much lower pace and currently represents 40% of all childhood mortality. Every year, 2.6 million neonates die; three-fourths of these deaths occur in the first week of life, and 99% occur in low-income and middle-income countries. Neonatal sepsis ranks third among causes of neonatal mortality. It comes after prematurity and perinatal asphyxia. Neonatal sepsis is responsible for 13% of all neonatal mortality, and 42% of deaths in the first week of life. In critically ill patients a hypermetabolic state exists, which is caused principally by the increased serum levels of counter-regulatory hormones and cytokines, such as tumor necrosis factor-α, interleukin-1, and interleukin-6, which may be important mediators of insulin resistance and hyperglycemia. In contrast, some neonates are at a risk of developing low blood glucose concentration, for example, preterm babies, large for gestational age, infants of diabetic mothers, intrauterine growth retardation, sepsis, shock, asphyxia, hypothermia, and respiratory distress syndrome. The aim of the present study was to assess the prevalence of plasma glucose abnormalities in infants with neonatal sepsis and the association between these abnormalities and both morbidity and mortality.
| Patients and Methods|| |
This was a prospective, observational study. The study protocol was approved by the ethics committee of Faculty of Medicine, Menoufia University. The study was conducted from April 2017 to March 2018 in the neonatal intensive care unit of Menoufia University Hospital and Benha Children Hospital. A total of 114 neonates having sepsis were included. Sepsis was defined as the presence of clinical signs and symptoms indicative of infection isolation of pathogens from the blood, cerebrospinal fluid, or urine. Probable sepsis was defined as the presence of clinical signs and symptoms of sepsis with one or more of these criteria; presence of a total leukocytes count of more than 30 000/mm3 or under 5000/mm3; positive C-reactive protein (>5 mg/dl); existence of predisposing factors, that is maternal fever or foul smelling liquor or prolonged rupture of membranes (>18 h).
The exclusion criteria included: (a) neonates less than 36 weeks of postmenstrual age, (b) babies more than 42 weeks of postmenstrual age, (c) infants of diabetic mothers, (d) cases who were initially suspected of sepsis or probable sepsis, but the investigations did not support the initial diagnosis. Glucose level was measured within 2 h of admission using Accu-Chek device (Roche Diabetes Care Inc., Basel, Switzerland), which measures the glucose level from a drop of blood from a heel prick and automatically gives the reading of plasma glucose. Patients were divided into three subgroups, namely those with hypoglycemia, hyperglycemia, and normoglycemia. Hypoglycemia was defined as plasma glucose level less than 50 mg/dl in the first 48 h and less than 60 mg/dl after 48 h of age. Hyperglycemia was defined as plasma glucose more than 145 mg/dl. All neonates were monitored till either discharge or neonatal intensive care unit mortality. Continuous variables with normal distribution were expressed as the mean ± SD, while quantitative variables with non-normal distribution were presented as median and range. t Test and 'analysis of variance' were used for comparing the means of normally distributed continuous variables as indicated. Quantitative variables with non-normal distribution were compared by Mann–Whitney U test and Kruskal–Wallis test as indicated. Qualitative data were analyzed by χ2 test or Fisher's exact test. The latter was utilized for 2 × 2 qualitative variables when more than 25% of the cells had an expected count of less than 5. Correlations between variables with normal and non-normal distribution were performed by Pearson's and Spearman's correlation, respectively. Logistic regression analysis was used to test the association of variables with mortality. A P value of less than 0.05 was considered statistically significant. Statistical analyses were performed using IBM statistical package for the social sciences (version 20; SPSS Inc., Chicago, Illinois, USA).
| Results|| |
One hundred fourteen neonates were recruited in the study. Their basic demographic, clinical, and laboratory data are shown in [Table 1]. This table shows also that nonsurvivors had a significantly lower platelet count, a significantly higher postnatal age, and a significantly higher mechanical ventilation rate.
Of the infants, 8.7% had hyperglycemia, while 8.7% had hypoglycemia, and 82.6% were normoglycemic. No significant difference in mortality rate was found among the infants with hyperglycemia, hypoglycemia, and normoglycemia. No significant difference was found among the three subgroups regarding other clinical and laboratory variables. There was no significant difference in mechanical ventilation rate and the length of hospital stay among the three subgroups [Table 2].
Through logistic regression analysis, no significant association was found between mortality and both hyperglycemia and hypoglycemia [Table 3].
|Table 3: Univariate logistic regression analysis for prediction of mortality by the glycemic status|
Click here to view
No correlation was found between glucose level and any of the clinical or laboratory variables [Table 4].
| Discussion|| |
Hypoglycemia is one of the most common metabolic derangements encountered in the neonatal age group. Sepsis has been known to be the cause of 9.6% cases of neonatal hypoglycemia. In the present study, 17.5% of infants had abnormal plasma glucose level; 8.7% had hypoglycemia; and 8.7%% had hyperglycemia. In a study made by Najati and Saboktakin, 14 168 newborns were recruited to determine the prevalence of neonatal hypoglycemia and its underlying causes. Prevalence of neonatal hypoglycemia was 0.4%. Sepsis was the third cause of hypoglycemia (9.6%) after prematurity and infants of diabetic mothers. In another study conducted on 62 infants with neonatal sepsis, 13.5% of infants had hypoglycemia on admission. In one study which included 502 neonates with culture-proved sepsis or probable sepsis, blood glucose levels were under 40 mg/dl in 50 (9.9%) patients. In another study, the prevalence of hypoglycemia in neonates with primary diagnosis of sepsis was 16.3%. In the study made by Mizock et al., the prevalence of hyperglycemia was 15.3%. Ahmed and Khalid found in their study that the glucose levels were above 200 mg/dl in 35 (6.9%) patients. In another study, the prevalence of hypoglycemia in neonates with primary diagnosis of sepsis was 16.3%. The prevalence of hyperglycemia in critically ill children in the first week of ICU was 53.9%. In the present study, it was observed that mortality in the hyperglycemic group was not significantly higher than mortality in the normoglycemic group. Islam et al. found a significantly higher mortality rate in the hyperglycemic group compared with the normoglycemic group (50 vs. 10.8%, P ≤ 0.05). The difference between our results and this study may be due to the small number of patients in the latter study. Another study conducted by Hays et al. showed that in extremely low birth weight infants, high blood glucose concentrations increased the risk of death. May be our current findings are discordant with the latter study due to the discrepancy in gestational age. It is to be noted that relevant studies on neonatal sepsis are few. However, studies in older children indicated an increased risk of mortality in parallel with the increase in glucose level. In a retrospective study made by Naranje et al., they did not find any significant association between isolated hyperglycemia and mortality. Our study found no significant association between hypoglycemia and mortality. In line with the present study, a small study of infants with neonatal sepsis found no significant difference in mortality between infants with hypoglycemia and those with normoglycemia. In contrast, a larger study found an association of a blood glucose level of less than 40 mg/dl was associated with mortality in infants with neonatal sepsis. However, the latter study did not mention the gestational age of their patients which could explain the discrepancy between their findings and ours. This study had a larger number of cases than our study and that is why the effect of hypoglycemia is more obvious on mortality, but the gestational age is not mentioned in the latter study. In our study, a gestational age of less than 36 weeks was excluded to avoid instability of the blood glucose level that happens in preterms. Our study concluded that there were no differences between hyperglycemic, hypoglycemic, and normoglycemic groups regarding the length of stay and need for invasive mechanical ventilation. In contrast to our findings, another study showed that hyperglycemia was associated with a longer length of hospital stay, but the latter study was conducted on extremely low birth weight infants. Another study reported an association between the maximal glucose level and the length of PICU stay. However, the latter study was conducted on pediatric patients beyond the neonatal period. The cohort study made by Naranje et al. did not show any significant association between isolated hyperglycemia and length of ICU stay. Continuous glucose monitoring may be more accurate and can settle the issue in the future. As far as we know, no previous study evaluated the relation between plasma glucose abnormalities and the need for invasive mechanical ventilation. It should be asked: What is the mechanism linking hyperglycemia to poor clinical outcome? It was shown that hyperglycemia causes hyperosmolality and osmotic diuresis. Hyperosomolality alters cerebral autoregulation. Hyperosmolar state can also cause water to move from the intracellular compartment to the extracellular compartment. The resultant contraction of intracellular volume of the brain may cause intracranial hemorrhage. Other mechanisms include enhanced apoptosis, increased production of cytokine, hypercoagulation, acute dyslipidemia, and endothelial dysfunction. A neonate having sepsis develops reluctance to feed and this can lead to hypoglycemia. Similarly increased metabolic demand and hypothermia caused by sepsis can bring down the glucose level. Significant hypoglycemia in neonates results in neurological impairment ranging from learning disabilities, seizure disorders to cerebral palsy. It may also cause mental retardation of varied severity. We recommend the following: screening for plasma glucose abnormalities should be performed for all full-term infants with neonatal sepsis on admission. Larger studies are needed to confirm the relation of glucose level abnormalities to mortality and morbidity. Larger studies are needed to determine the exact level of glucose that defines hyperglycemia and hypoglycemia. Randomized, controlled trials are needed to confirm whether glucose abnormalities are really harmful to the neonate or they just represent epiphenomena.
| Conclusion|| |
Our findings indicate that plasma glucose abnormalities, including hypoglycemia and hyperglycemia, are not uncommon among full-term neonates with sepsis. However, these abnormalities are not associated with mortality or morbidity. Larger studies are needed to confirm these findings.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Qazi SA, Stoll BJ. Neonatal sepsis: a major global public health challenge. Pediatr Infect Dis J 2009; 28
Tissieres P, Ochoda A, Dunn-Siegrist I, Drifte G, Morales M, Pfister R, et al
. Innate immune deficiency of extremely premature neonates can be reversed by interferon-g. PLoS One 2012; 7
Boghossian NS, Page GP, Bell EF, Stoll BJ, Murray JC, Cotten CM, et al
. Late-onset sepsis in very low birth weight infants from singleton and multiple-gestation births. J Pediatr 2013; 162
Shim GH, Kim SD, Kim HS, Kim ES, Lee HJ, Choi CW, et al
. Trends in epidemiology of neonatal sepsis in a tertiary center in Korea: a 26-year longitudinal analysis, 1980–2005. J Korean Med Sci 2011; 26
Simonsen KA, Anderson-Berry AL, Delair SF, Davies HD. Early-onset neonatal sepsis. Clin Microbiol Rev 2014; 27
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Crit Care Med 2005; 6
Woldu MA, Guta MB, Lenjisa JL, Tegegne GT, Tesafye G. Assessment of the incidence of neonatal sepsis, its risk factors, antimicrobials use and clinical outcomes in bishoftu general hospital, neonatal intensive care unit, Debrezeit-Ethiopia. Pediat Therapeut 2014; 4
Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013; 60
Wang H, Liddell CA, Coates MM, Mooney MD, Levitz CE, Schumacher AE, et al
. Global, regional, and national levels of neonatal, infant, and under-5 mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384
Liu L, Johnson HL, Cousens S, Perin J, Scott S, Lawn JE, et al
. Global, regional, and national causes of child mortality: an updated systematic analysis for 2010 with time trends since 2000. Lancet 2012; 379
McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin 2001; 17
Mizock BA. Alterations in fuel metabolism in critical illness: hyperglycaemia. Best Pract Res Clin Endocrinol Metab 2001; 15
Wilker RE. Hypoglycemia and hyperglycemia. In: Cloherty JP, Eichenwald EC, Stark AR, eds. Manual of neonatal care. 6th
ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2008. 540–549.
Zea-Vera A, Ochoa TJ. Challenges in the diagnosis and management of neonatal sepsis. J Trop Pediatr 2015; 61
Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008; 36
Thornton PS, Stanley CA, De Leon DD, Harris D, Haymond MW, Hussian K, et al
. Recommendations from the pediatric endocrine society for evaluation and management of persistent hypoglycemia in neonates, infants, and children. J Pediatr 2015; 167
Harris DL, Battin MR, Weston PJ, Harding JE. Continuous glucose monitoring in newborn babies at risk of hypoglycemia. J Pediatr 2010; 157
Najati N, Saboktakin L. Prevalence and underlying etiologies of neonatal hypoglycemia. Pak J Biol Sci 2010; 13
Islam MS, Mia MA, Rokshanaakhter K, Haque M, Malik M. Glycemic status and its effect in neonatal sepsis in a tertiary care hospital. Bangladesh J Child Health 2016; 40
Ahmed S, Khalid R. Blood glucose levels in neonatal sepsis and probable sepsis and its association with mortality. J Coll Physicians Surg Pak 2012; 22
Sadi-Nezhad M. Study of prevalence of hypoglycemia in neonates with primary diagnodiss of sepsis. yafte 2004; 5
Naranje KM, Poddar B, Bhriguvanshi A, Lal R, Azim A, Singh RK, et al
. Blood glucose variability and outcomes in critically ill children. Indian J Crit Care Med 2017; 21
Hays SP, Smith EO, Sunehag AL. Hyperglycemia is a risk factor for early death and morbidity in extremely low birth weight infants. Pediatrics 2006; 118
Wintergerst KA, Buckingham B, Gandrud L, Wong BJ, Kache S, Wilson DM. Association of hypoglycemia, hyperglycemia, and glucose variability with morbidity and death in the pediatric intensive care unit. Pediatrics 2006; 118
Rozance PJ, Hay WW Jr. Describing hypoglycemia—definition or operational threshold? Early Hum Dev 2010;86
[Table 1], [Table 2], [Table 3], [Table 4]