In the present study, abnormalities in the admission plasma glucose level were not uncommon in infants with neonatal sepsis which lends support to the routine practice of measuring glucose level to these infants upon NICU admission.
Unlike hypoglycemia, which is a well-known manifestation of neonatal sepsis, hyperglycemia has received much less attention. However, in one study, hyperglycemia was reported among 24.6% of infants admitted into NICU, with sepsis accounting for 78.8% of hyperglycemia cases, but no data was given about the specific prevalence of hyperglycemia among infants with sepsis .
In another study, 6.9% of infants with neonatal sepsis had a blood glucose level over 200 mg/dL whereas 9.9% had a glucose level under 40 mg/dL . The lower frequency of glucose abnormalities in the latter study, compared with ours, might be related to differences in the definitions of hypoglycemia and hyperglycemia or to a discrepancy in gestational age which was, unfortunately, not reported by the latter study.
There is adequate awareness of the dangers of neonatal hypoglycemia which is routinely screened for and immediately treated among sick neonates since it is frequently associated with short-term and long-term serious clinical consequences. Furthermore, in an infant with a diagnosis of sepsis, some signs like lethargy, poor feeding, and apnea may be erroneously attributed to the sepsis process itself although they may be a manifestation of an associated unrecognized hypoglycemia which might itself be harmful if left untreated.
In contrast, hyperglycemia does not trigger a similar alarm response on the part of health care workers and is frequently left untreated because it is thought to produce no serious problems. However, our current findings do not support this practice as it turned out that the mortality rate among the hyperglycemic subgroup was significantly higher compared with that among the normoglycemic ones. Besides, hyperglycemia was an independent predictor of mortality with an odds ratio of 2.89.
Previous studies of neonatal hyperglycemia predominantly targeted very premature infants, whether or not having sepsis, and demonstrated a clear association of hyperglycemia with mortality [12, 20, 21]. In contrast, there is a dearth of data concerning the impact of hyperglycemia on full-term and late-preterm neonates with sepsis. In the only report we were able to retrieve , septic neonates with an admission blood glucose level > 200 mg/dL and those with a level < 40 mg/dL had a significantly higher mortality rate compared with the other infants but the authors did not tell about the gestational age of their cohort.
As for morbidity, no association was found, in the present study, between hyperglycemia and the need for mechanical ventilation or the length of NICU stay, which is consistent with a previous study of extremely low birth weight (ELBW) infants  although another study of ELBW infants reported an association of hyperglycemia with the length of NICU stay .
The pathogenic effects of hyperglycemia could be mediated by increased oxidative stress or by a pro-inflammatory state resulting from the high glucose level. Furthermore, hyperglycemia possesses a pro-thrombotic effect and reduces endothelial nitric oxide, thus decreasing tissue perfusion . Moreover, there are concerns about the potential deleterious consequences of hyperglycemia on the developing brain as indicated by clinical  and experimental  studies. The latter effects could be attributed to hyperglycemia-induced oxidative stress  which can, in turn, produce neuronal apoptosis .
An interesting finding in the present study was the observation of a significantly higher mortality rate among infants with moderate/severe hyperglycemia compared with those having normoglycemia. Meanwhile, no significant difference in mortality was found between infants with mild hyperglycemia and those with normoglycemia. These relations could signify, if confirmed in larger cohorts, that the upper safe limit of glucose concentration in neonatal sepsis might be closer to 180 mg/dL rather than 145 mg/dL. This is supported by recent meta-analyses of randomized controlled trials performed in critically ill pediatric patients which failed to demonstrate a survival benefit from tight glycemic control [26, 27]. Similarly, the most recent adult sepsis guidelines recommend treating hyperglycemia with insulin infusion only if two consecutive blood glucose levels are > 180 mg/dL . Likewise, there has been a strong trend among neonatologists to define hyperglycemia as a blood glucose above 180 mg/dL .
It should be stressed that observational studies, including ours, are not sufficient alone to define the safe upper glucose level in neonates because it is quite possible that hyperglycemia might not be the cause of mortality and morbidity but just an epiphenomenon indicating that sepsis is severe. Undoubtedly, randomized controlled trials are needed to settle that issue. Another important point that needs to be taken into consideration is that tight glycemic control carries the risk of hypoglycemia as shown by recent meta-analyses [26, 27]. Regardless of this controversy, hyperglycemia appears to be useful for predicting mortality in neonatal sepsis.
Compared with hyperglycemia, hypoglycemia was found, in the present study, to have a more evident association with mortality (adjusted odds ratio = 3.86). Moreover, infants with hypoglycemia were more likely to need invasive mechanical ventilation. In addition, hypoglycemia was associated with a significantly lower platelet count which is a prognostic marker in neonatal sepsis . Although hypoglycemia might not be causally linked to these effects, our findings indicate that it is a good prognostic tool that should warn physicians of an unfavorable clinical outcome so that more close monitoring and aggressive treatment would be instituted.
Noteworthy, the postnatal age was significantly higher among non-survivors which could be explained by the fact that a significant number of infants are referred to our NICU from other hospitals after a lag of several days when a place is available. This delay made the age of referred infants older and, meanwhile, might have contributed to their mortality.
There are several limitations of the present study. The sample sizes were not large enough to draw firm conclusions. In addition, we used a single glucose measurement upon NICU admission rather than the mean or peak levels over a prolonged period. However, a single measurement seems to be a simpler tool that can be readily utilized by physicians to predict the prognosis. Besides, we measured plasma glucose level by blood glucose meter whose results are not as reliable as those of formal laboratory testing. Finally, the observational nature of the present study cannot prove the causal relation of glucose abnormalities to mortality and morbidity. Randomized controlled trials are, therefore, certainly needed.