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ORIGINAL ARTICLE
Year : 2020  |  Volume : 23  |  Issue : 1  |  Page : 71-78

Prevalence, risk factors, and outcome of hospitalization of neonatal hyperglycemia at a Nigerian health facility


1 Department of Paediatrics, Wesley Guild Hospital, Ilesa, Nigeria
2 Department of Paediatrics and Child Health, Obafemi Awolowo University, Ile-Ife, Nigeria

Date of Submission24-Apr-2019
Date of Acceptance07-Oct-2019
Date of Web Publication10-Jan-2020

Correspondence Address:
Dr. E O Adeniji
P.O. BOX 754, Osogbo, Osun State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/njcp.njcp_229_19

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   Abstract 


Background: Neonatal hyperglycemia (NNH) like hypoglycemia is a dangerous metabolic disorder often associated with adverse consequences, if undetected and untreated. This study was set out to determine the prevalence, risk factors, and outcomes of babies with the point of admission hyperglycaemia at the Wesley Guild Hospital (WGH), Ilesa. Methods: The study was descriptive and cross-sectional, involving 300 consecutively recruited neonates admitted into the special care baby unit (SCBU) of the hospital. All subjects had blood glucose done at the point of admission using Accu-Chek Active® glucometer (Roche Diagnostics GmbH, Germany). Hyperglycemia was defined as blood glucose ≥7.0 mmol/L. Factors associated with NNH were determined using univariate and multivariate analyses. Results: Of the 300 subjects (Male: Female 1.5:1), there were 74 (24.7%) preterms, 35 (11.7%) small-for-gestational age and 85 (28.3%) low-birth-weight babies. Eighteen (6.0%) babies had hyperglycemia. Parental low socioeconomic class, maternal lack of antenatal care (ANC), vaginal delivery, grand multiparity, outborn status, respiratory distress, probable sepsis, and neonatal anemia at presentation were associated with NNH (P < 0.05). Respiratory distress (OR = 3.800, 95% CI = 1.122-12.873, P = 0.032), and probable sepsis (OR = 4.090, 95% CI = 1.206-13.872, P = 0.024) were independent predictors of hyperglycemia. Hyperglycemia was significantly associated with mortality. (38.9% vs. 11.0%; P = 0.001). Conclusion: Neonatal hyperglycemia was detected in 6.0% of neonatal admission at the WGH, Ilesa and it was associated with increased mortality. Hyperglycemia should be suspected and promptly managed at the point of admission of ill newborns particularly those with respiratory distress and signs of sepsis.

Keywords: Hyperglycemia, neonates, respiratory distress, risk factors, sepsis


How to cite this article:
Adeniji E O, Kuti B P, E Elusiyan JB. Prevalence, risk factors, and outcome of hospitalization of neonatal hyperglycemia at a Nigerian health facility. Niger J Clin Pract 2020;23:71-8

How to cite this URL:
Adeniji E O, Kuti B P, E Elusiyan JB. Prevalence, risk factors, and outcome of hospitalization of neonatal hyperglycemia at a Nigerian health facility. Niger J Clin Pract [serial online] 2020 [cited 2020 Jul 13];23:71-8. Available from: http://www.njcponline.com/text.asp?2020/23/1/71/275614




   Introduction Top


Neonatal hyperglycemia (NNH) is a common metabolic abnormality particularly encountered in preterm and ill newborns.[1],[2] It is becoming an increasingly significant secondary cause of morbidity and mortality in the newborn. This is particularly so in extreme low birth weight (ELBW) or extreme preterm babies whose chances of survival are increasing with the availability of improved techniques and facilities for care.[3]

The maintenance of normoglycemia in neonates depends upon the adequacy of glycogen stores, maturation of glycogenolytic, and gluconeogenic pathways, and integrated endocrine response.[2] Glucose homeostasis requires a balance between the utilization and production of glucose from the liver. The balance is controlled by insulin and counter-regulatory hormones.[2]

Historically, hyperglycemia has been attributed majorly to excessive intravenous glucose infusions but recent studies showed that there are physiologic and biochemical mechanisms in ill babies which may result in excess glucose production, glucose intolerance or insulin resistance.[3] These factors interfere with glucose homeostasis, particularly in preterm low birth weight (LBW) infants.[3] Other reported predisposing factors for NNH include birth asphyxia and neonatal sepsis which are major causes of neonatal morbidity and mortality, particularly in developing countries.[4]

The prevalence of NNH varies in different studies depending on the blood glucose cut-off used and patient characteristics such as gestational age and birth weight. It also varies with time of sample collection i.e. at point of admission or during hospital admission. The reported prevalence of NNH by Beardsall et al.[5] in Europe ranges between 32.0–86.0% in very low birth weight (VLBW) infants who were on parenteral nutrition and/or intravenous dextrose infusion.[5] Hays et al.[6] and Farrag and Cowett[7] in the United States of America, reported a prevalence of 57.0% and 68.0%, respectively among ELBW babies also on dextrose infusions. However, Nalini et al.[8] in India using higher blood glucose cut off of 8.3 mmol/L at admission (before intervention) reported a low prevalence (0.94%) among all neonatal admissions but a much higher rate (2.9%) among VLBW babies. In Nigeria, Dedeke et al.[9]reported that 5.0% of all categories of hospitalized babies had NNH at the point of admission using the same cut-off blood glucose of 8.3 mmol/L.[9] Also in Nigeria, Onyiriuka and Enyi[10] reported prevalence rates of 32.6% among VLBW babies whose blood glucose was monitored while on admission in a tertiary healthcare facility.

Neonatal hyperglycemia has been largely understudied because more emphasis is often placed on hypoglycemia which has been widely reported to be associated with both immediate and long-term neurodevelopmental disability and mortality.[2],[11],[12] However, hyperglycemia can also lead to complications which include osmotic dehydration, intracranial hemorrhage, and increased susceptibility to infections.[2],[13] All these can contribute significantly to neonatal morbidity and mortality.[1],[13] The current study, therefore, aimed to determine the prevalence of the point of admission of hyperglycemia, its associated risk factors, and the outcome of hospitalization of babies admitted to the SCBU of the WGH, Ilesa, Osun State, Nigeria.


   Subjects and Methods Top


This descriptive and cross-sectional study was carried out at the SCBU of the WGH, Ilesa, Osun State, southwest Nigeria. The WGH is one of the units of the Obafemi Awolowo University Teaching Hospital Complex (OAUTHC). The SCBU consists of eight glass-walled cubicles that can admit up to 32 babies. It is equipped with incubators and phototherapy units but has no facilities for total parenteral nutrition or automated mechanical ventilation. The ward is manned by six clinicians including a consultant pediatrician, three resident doctors, and two house officers. Twenty- four hour coverage is ensured with complement of 15 nurses (who run shift duty) and other supportive staffs. Three hundred babies aged ≤28 days admitted to the SCBU of the WGH irrespective of gestational age, birth weight, and initial diagnosis were consecutively recruited at the time of presentation into the SCBU. Exclusion criteria were major congenital anomalies or parental refusal of consent. Ethical approval for the study was obtained from the Ethics and Research Committee of the OAUTHC.

Sample size determination

The minimum number “n” of babies required for the study was calculated using the formula below to estimate the sample size in a prevalence study.[14]

n = z2 P (1-p)/d2

where:

z is the critical value and is equal to 1.96 for a 95% confidence interval.

p is the estimated prevalence of neonatal hyperglycemia which is taken as 5%.[9]

d is the absolute sampling error that can be tolerated, it was fixed at 2.5%

Therefore, the minimum sample size n = 1.962 × 0.05 (1-0.05)/0.0252 = 291.

The calculated sample size was rounded up to 300.

History obtained about the recruited babies included the age at presentation, parental socioeconomic status assessed by finding the average scores of the father and mother's occupation and level of education (using Oyedeji's classification),[15] place of antenatal care, place of delivery, mode of delivery, and the mother's parity were documented in the proforma designed for the study. Each baby was weighed and examined for abnormal clinical signs such as respiratory distress and jaundice.

The weights of the babies were classified into normal (2500 to 3999 g), macrosomia (≥4000 g), and LBW (<2500 g). The LBW babies were further subclassified into VLBW (1000 to 1499 g) and ELBW (<1000 g).[16] The babies were also classified using Lubchenko charts into small-for-gestational age (SGA) when the weight was less than 10th percentile of the expected for the gestational age, appropriate-for-gestational age (AGA) when the weight is between 10th and 90th percentiles, and large-for-gestational age (LGA) when weight is >90th percentile using an intrauterine growth chart.[16] Babies were also classified as preterm, term, and post-term when the gestational ages were <37 weeks, 37 to 42 weeks and above 42 weeks, respectively. Diagnosis related to sepsis were classified as presumed sepsis, probable sepsis, and confirmed sepsis. Babies with probable sepsis were babies with clinical features to suggest sepsis such as fever, hypothermia, poor suck, lethargy, respiratory distress, and so on.[17] Presumed sepsis was diagnosed in babies with one or more risk factors to suggest sepsis including prolonged rupture of membrane, peripartum fever, or chorioamnionitis but who had not yet manifested clinical features of sepsis.[17] Babies with confirmed sepsis not only had risk factors or clinical features of sepsis but they also had bacteria growth on blood culture.[17] Respiratory distress was defined by presence of any of the following features; tachypnoea, flaring of alae nasi, intercostal recession, subcostal recession, substernal recession, grunting, or apnoea.

A drop of venous blood was used for cot-side estimation of blood glucose using the Accu-Chek Active® glucometer (Roche Diagnostics GmbH, Germany) at the point of admission into the SCBU. Blood glucose values ≥7.0 mmol/L were taken as hyperglycemia while values <2.2 mmol/L were taken as hypoglycemia.[2] Babies with hyperglycemia were further classified into mild (blood glucose 7.0 to 9.9 mmol/L), moderate (10 to 15 mmol/L), and severe (>15 mmol/L).[10] Babies with hyperglycemia had their blood glucose monitored hourly until two normal blood glucose values were obtained.[3] The babies were managed with intravenous 5% dextrose water (for babies <48 h) or 4.3% dextrose saline for those older than 48 h in addition to treatment of the underlying condition.[18] Insulin therapy was to be considered if hyperglycemia persisted >13.9 mmol/L for more than 48 h and possibility of neonatal diabetes mellitus in such patients.[19] The subjects were monitored until the end of hospitalization and their outcomes (length of hospitalization, discharged, died, discharged against medical advice (DAMA), or referred) documented. The final diagnosis was determined by the researchers who were also the clinical team managing the babies.

Data analysis

This was done using the Statistical Package for Social Sciences (SPSS) for Windows version 23.0. (IBM Corp. Armonk 2015, NY, USA) Descriptive statistics including measures of central tendency like mean with standard deviation (SD) and median with interquartile range (IQR) were used to summarize normally and non-normally distributed continuous variables, respectively, while proportions and percentages were used to summarize categorical variables such as sex and age ranges. Categorical variables were compared using Pearson's Chi-square (χ2) and Fisher's exact test as appropriate. Pearson's correlation was used to determine relationship between blood glucose and the gestational ages of the babies. Logistic regression analysis was used to determine independent predictors of NNH. The relationship between age at presentation (which was not normally distributed) and blood glucose categories was assessed using Kruskal Wallis test (k). Statistical significance was set at P value < 0.05 at 95% confidence interval.


   Results Top


Over a 6-month study period (January to June 2017), 300 babies who met the inclusion criteria were consecutively recruited into the study.

Neonatal data

There were 179 (59.7%) males and 121 (40.3%) females among the study participants giving a male to female ratio of 1.5: 1. The mean (SD) GA of the babies was 37.7 (2.9) weeks with a range of 26 to 44 weeks.

Two hundred and eighteen (72.6%) of the babies were born at term, 74 (24.7%) were preterm and 8 (2.7%) were post-term. The mean (SD) weight of the babies was 2.8 (0.8) kg with range of 0.6 to 4.5 kg. The majority (68.0%) of the babies had normal birth weight, 85 (28.3%) were LBW (including 13 VLBW and three ELBW). Two hundred and fifty-four (84.6%) of the babies were AGA, 35 (11.7%) were SGA and 11 (3.7%) were LGA.

The median (IQR) age at presentation was 10.0 (0.5–70.0) h. The majority (59.0%) of the babies presented within 24 hours of life, 51 (17.0%) babies presented between 24 and 71 hours of age, while 37 (12.3%) and 35 (11.7%) presented between 72 and 167 hours of life and after 7 days of life, respectively.

Parental socioeconomic class

: One hundred and fifty-eight (52.7%) of subjects were born to parents from the middle socioeconomic class: 111 (37.0%) to parents from the upper class and 31 (10.3%) to low socioeconomic class parents.

Maternal data

The mean (SD) maternal age was 29.4 (6.2) years with a range of 17 to 51 years. The highest proportion (82.4%) of the mothers were in the age range 20 to 35 years. Ten (3.3%) mothers were teenagers while 43 (14.3%) were older than 35 years. Maternal parity ranged from one to seven with a mean (SD) of 2.2 (1.3). One hundred and twenty (40.0%) of the mothers were primiparous, 162 (54.0%) were multiparous while the remaining 18 (6.0%) were grand multiparous. The mothers of 123 (41.0%) babies received ANC at the WGH. One hundred and forty-six (48.7%) babies were delivered at the WGH (inborn) while the remaining 154 (51.3%) were delivered elsewhere. Among the outborns, 58 (37.7%) were delivered at maternity centers, 47 (30.5%) at private hospitals, 25 (16.2%) at general hospitals while 15 (9.7%) at mission houses, and 9 (5.8%) were delivered at home. One hundred and eighty-three (61.0%) of the babies were delivered by the vaginal route while the remaining 117 (39.0%) were delivered through a cesarian section.

Clinical diagnosis at admission

[Table 1] shows the relative frequencies of clinical diagnosis on admission. Perinatal asphyxia was the leading diagnosis followed by suspected sepsis. Eighty-five (28.3%) babies were low birth weight while 63 (21.0%) had neonatal anemia.
Table 1: Clinical diagnosis of the 300 babies at presentation

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Blood glucose measurements

The mean (SD) blood glucose at point of admission was 4.1 (2.1) mmol/L (range: 0.6 to 13.4 mmol/L). Of the 300 subjects, 18 (6.0%) had neonatal hyperglycemia, 40 (13.3%) had hypoglycemia while the remaining 242 (80.7%) babies had normal blood glucose levels. Further classifying the severity of neonatal hyperglycemia in the 18 babies showed 13 (72.2%) had mild and five (27.8%) were moderate cases. The mean (SD) duration of hyperglycemia before successful correction in the babies was 2.9 (2.4) hours with a range of 1 to 8 hours. None of the five (1.2%) babies that were given intravenous dextrose infusion from the referring centers had hyperglycemia. All but two of the 18 cases of hyperglycemia were successfully treated with infusions of low glucose: two babies died while corrective treatment was still ongoing.

Association between sociodemographic characteristics and the presence of hyperglycemia

Two (1.8%) of the 111 babies from upper socioeconomic class had hyperglycemia compared to 10 (6.3%) of the 158 babies and 6 (19.4%) of the 31 babies from middle and low socioeconomic class, respectively. The babies from the low socioeconomic class were significantly more likely to have NNH at presentation whereas the babies from upper class were less likely to have hyperglycemia at presentation (χ2 = 11.135, P = 0.004). The age of the babies and sex were not significantly related to the presence of hyperglycemia. Details are summarized in [Table 2].
Table 2: Association between sociodemographic characteristics and the presence of hyperglycemia

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Frequency of hyperglycemia in relation to gestational age and weight

In the respective subgroups, NNH was most prevalent among post-term babies, normal-weight babies and appropriate-for-gestational age babies [Table 3]. None of the VLBW, ELBW and macrosomic babies had neonatal hyperglycemia at presentation. The weight of the babies, gestational ages and the weight for gestational ages were not significantly associated with NNH (P > 0.05).
Table 3: Frequency of hyperglycemia in relation to gestational age and weight

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Frequency of hyperglycemia in relation to maternal characteristics

The babies of grand multiparous women and those delivered through the vaginal route are significantly at risk of hyperglycemia (P-value < 0.05). Also babies whose mothers received ANC or were delivered elsewhere had higher risk of hyperglycemia (P-value < 0.05). These are summarized in [Table 4].
Table 4: Frequency of hyperglycemia in relation to maternal characteristics

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Respiratory distress at admission

Respiratory distress was present in 131 (43.7%) of the recruited babies. Of the 131 babies with respiratory distress at point of admission, 13 (9.9%) had NNH compared to five (3.0%) out of the 169 without respiratory distress. Presence of respiratory distress in the babies constituted significant risk factor for NNH (χ2 = 6.348, P = 0.012).

Association between clinical diagnosis and hyperglycemia

Of all the various clinical diagnoses, babies with probable sepsis and anemia at admission were at higher risk of hyperglycemia (χ2 = 8.977, P = 0.003; χ2 = 6.344, P = 0.012, respectively). The presence of birth asphyxia, LBW, neonatal seizures, transient tachypnoea of newborn, aspiration pneumonitis, congestive cardiac failure, polycythemia, and jaundice was not significantly associated with presence of hyperglycemia at admission. The details as presented in [Table 5].
Table 5: Various clinical diagnosis and the relationship with hyperglycemia

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Binary regression of predictors of neonatal hyperglycemia among the neonates

Logistic regression was applied to determine the independent predictors of hyperglycemia [Table 6]. The potential explanatory variables were factors that showed significant association with NNH on bivariate analysis – see [Table 2], [Table 4] and [Table 5]. Those factors were low socioeconomic class, grand multiparity in the mother, outborn, unbooked status in mother, vaginal delivery, respiratory distress, anemia, and probable sepsis. Respiratory distress irrespective of the cause and probable sepsis emerged as independent predictors of NNH (OR = 3.800, 95% CI = 1.122-12.873, P = 0.032; OR = 4.090, 95% CI = 1.206-13.872, P = 0.024 respectively).
Table 6: Independent risk factors for NNH using the binary logistic regression analysis

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Hyperglycemia and relationship with outcome

The median (IQR) duration of admission for all the babies was 4.7 (2.6 to 7.0) days. Two hundred and forty-six (82.0%) babies were discharged home while 36 (12.0%) died on admission. Four (1.3%) were transferred to another facility while 14 (4.7%) were taken away against medical advice. Seven (38.9%) the 18 babies who had hyperglycemia died compared to 29 (11.0%) of the babies without hyperglycemia (χ2 = 10.542, P = 0.001). The median (IQR) length of hospitalization for the hyperglycemic, normoglycemic and hypoglycemic babies were 4.4 (0.3–6.8), 4.7 (2.8–7.0), and 4.2 (1.5–8.3) days, respectively (k = 2.004, P = 0.367).


   Discussion Top


The observed hospital prevalence of point of admission NNH of 6.0% was earlier reported as 5.0% from the same center more than 10 years ago.[9] It is, however, higher than 0.94% found by Nalini et al.[8] in India. Nalini et al.[8] applied higher cut-off glucose levels of 8.3 mmol/L mmol/L for preterm babies. As such, the study has excluded some babies who would have been classified as hyperglycemic with the cut-off of 7 mmol/L used in the current study. Onyiriuka et al.[10] reported a higher prevalence of 32.6% among VLBW babies admitted into a tertiary hospital elsewhere in Nigeria in contrast with the zero prevalence herein reported. The difference is readily explained by methodological differences. Whereas the current study estimated blood glucose at the point of admission, before any interventions, the subjects in the study by Onyiriuka et al.[10] were already on admission receiving dextrose infusions. A similar reason explains the much higher prevalence rates of 57% and 68% documented by Hays et al.[6] and Farrag et al.[7] both in USA. The ELBW babies in both of those studies were receiving intravenous glucose infusion or total parenteral nutrition. This underscores the fact that hyperglycemia in the newborn is often iatrogenic.[10]

Respiratory distress increased the risk of NNH by a factor of 3.8. This is in keeping with the findings of Van der Lugt et al.[1] This is possible because respiratory distress and the associated increase in the work of breathing, being a cause of stress can lead to increased production of counter-regulatory hormones which in turn trigger hepatic gluconeogenesis and glycogenolysis resulting in raised blood glucose levels.[20] The reverse relationship is also plausible as excess blood glucose can suppress surfactant production hence causing respiratory distress.[21]

In the present study, the increased risk of hyperglycemia with probable sepsis is in keeping with the finding of Van der Lugt et al.[1] This is because sepsis is a stressful condition to the babies is potentially associated with increased levels of cortisol, and catecholamines.[22] These hormones cause increased glycogenolysis and gluconeogenesis leading to increased glucose levels in the blood.[22] Also, in babies with sepsis, there is release of endotoxins and cytokines including interleukin-1, interleukin-6, and tumor necrotic factor-α which tend to oppose insulin actions.[22] Surprisingly, confirmed sepsis did not constitute a significant risk for hyperglycemia. This is possible because of the small number of confirmed cases of sepsis in the babies.

The risk of NNH was not significantly increased in babies who had birth asphyxia. This is in keeping with the finding of Akmal et al.[23] but contrary to the report of Sabzehei et al.[24] Although birth asphyxia is a known risk factor for NNH,[25] it is not surprising that it is not significantly associated with NNH. Most of the babies were outborns, and it is possible that before those babies got to the WGH, compensatory mechanisms had been set in motion if there was NNH initially. Such compensatory mechanisms include increase serum insulin whose ultimate result is to bring back to normal the serum blood glucose.[26]

The risk of death from NNH is consistent with reports from other studies.[1],[6] Hyperglycemia can increase the risk of mortality as a result of complications like intracranial hemorrhage, osmotic diuresis, dehydration, and late-onset of neonatal sepsis.[2],[13] The hyperosmolarity caused by hyperglycemia can cause movement of water from the intracellular compartment to extracellular compartment resulting in contraction of intracellular brain volume which can lead to intracranial hemorrhage.[27] This underlines the need for early detection of NNH.

A limitation of this study was the inability to confirm the presence of speculative associations between NNH on the one hand, and counter-regulatory hormones, or intraventricular hemorrhage on the other.


   Conclusion Top


Hyperglycemia is not uncommon among babies admitted to SCBU and it is significantly associated with mortality. Babies with respiratory distress and probable sepsis had more than three-fold likelihood of hyperglycemia. A high index of suspicion is required to make a diagnosis and institute interventions to improve outcomes.

Acknowledgments

The authors hereby acknowledge the contributions of the clinicians and other health professionals who were involved in the management of the babies admitted into the Special Care Baby Unit, WGH, Ilesa. We also acknowledge the babies and the parents/guardians who participated in the study.

Financial support and sponsorship

Personal.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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