Introduction

Neonatal hypoglycemia is characterized by a lower-than-normal blood glucose level1, which is a plasma glucose level of less than 30 mg/dL in the first 24 h of birth and less than 45 mg/dL in the last 24 h of life2. Prematurity, small for gestational age, prenatal hypoxia, and neonates delivered to diabetic moms are all at risk for neonatal hypoglycemia3,4.

Preterm neonates are particularly susceptible to developing hypoglycemia and its associated complications because of their low glycogen and fat reserves, inability to produce new glucose through gluconeogenesis pathways, higher metabolic demands brought on by their relatively larger brains, and inability to mount a counter-regulatory response to hypoglycemia5,6.

In many circumstances, preventing hypoglycemia is the most critical event during the prenatal to neonatal transition period7. However, hypoglycemia is the most prevalent metabolic abnormality in the newborn period4,8, which is linked to increased neonatal morbidity and mortality3.

If left untreated, persistent or recurrent hypoglycemia can have serious neurologic and developmental consequences9,10. Moreover, chronic hypoglycemia causes long-term neurodevelopmental problems, cerebral palsy, and mortality in the neonatal era9,11. Hence, early detection of recurrent or chronic hypoglycemia is crucial to improving the survival of neonates9,12,13,14.

The challenges to diagnosis and preventing neonatal hypoglycemia are due to their numerous and unclear symptoms15,16,17, which cause common neonatal complications, such as severe malaria, bacterial sepsis, severe malnutrition, and newborn sickness7,18,19. Hence, healthcare providers must be on the lookout for all possible indicators of neonatal hypoglycemia with risk factors to maximize detection and treatment of neonates with hypoglycemia20.

Although the prevalence of neonatal hypoglycemia varies depending on the definition, demographic, feeding method, timing, and type of glucose test used2,10. The overall incidence of hypoglycemia in neonates ranges from 1.3 to 3 per 1000 live births10, with risk groups ranging from 30 to 60%8,11.

In Ethiopia, the burden of neonatal hypoglycemia is very high8,10, and it is also interlinked with numerous neonatal complications and mortality3,9. In this regard, screening and managing neonatal hypoglycemia is a challenge for healthcare providers in the neonatal intensive care unit11,17,19. Thus, data is essential to recognizing and managing hypoglycemia in preterm neonates. However, there are no sufficient studies conducted in Ethiopia in general and in the study setting in particular in the previous era. Hence, this study aims to assess the rate of hypoglycemia and associated factors among preterm neonates admitted to the Neonatal Intensive Care Unit at Debre Tabor Comprehensive Specialized Hospital, Northcentral, Ethiopia, in 2021.

Methods and materials

Study setting and study design

A hospital-based cross-sectional study was conducted from October 1 to December 30, 2021, at Debre Tabor Comprehensive Specialized Hospital in the Neonatal Intensive Care Unit ward. The hospital is located 670 km from Addis Ababa, the capital city of Ethiopia21.

Study participants

All preterm neonates admitted to the neonatal intensive care unit from October 1 to December 30, 2021, at Debre Tabor Comprehensive Specialized Hospital were eligible for the study. Preterm neonates admitted without mothers or caregivers were excluded in the study. Sampling size and.

Sampling procedure

The sample size was determined using the single population proportion formula by considering the following assumptions: 95% confidence interval, 5% margin of error (d), and taking the p value from the previous study conducted in St. Paul’s Hospital Millennium Medical College Neonatal Intensive Care Unit, Ethiopia8.

$$n = \frac{{\left( {z_{a/2} } \right)^{2} \times p\left( {1 - p} \right)}}{{d^{2} }}n = \frac{{\left( {1.96} \right)^{2} \times 0.25\left( {1 - 0.75} \right)}}{{0.05^{2} }} = 289$$

Therefore, the final sample size after adding 5% was 304. However, there were 279 preterm neonates admitted and meeting the inclusion criteria at Debre Tabor Comprehensive Specialized Hospital between October 1 and December 30, 2021.Hence, we included all preterm neonates admitted to the neonatal intensive care unit at Debre Tabor Comprehensive Specialized Hospital during the study period.

Data collection tools and procedures

The data was collected by interviewing mothers and caregivers. Besides, the clinically relevant information was obtained from the medical records of the neonate. The abstraction tool contained socio-demographic, obstetrics, and preterm neonate-related characteristics that enabled the evaluation of the outcome variable. At first, the abstraction tool was developed in English and translated into the local language, Amharic, and then back to English to keep consistency.

Operational definitions

Hypoglycemia is defined as a plasma glucose level of less than 47 mg/dL during the study period22.

Hypothermia is defined as an abnormal thermal state in which the newborn's body temperature drops below 36.5 °C23.

Preterm refers to a baby born before 37 weeks of pregnancy have been completed24.

Birth asphyxia is defined as a profound metabolic or mixed acidemia, the persistence of an Apgar score of 0–3 for longer than 5 min25.

Neonatal sepsis is defined as a clinical sign with the presence of risk factors, lab tests, or confirmed by blood culture25.

Statistical analysis

The data was entered in Epi-info 7 and exported to STATA version 14. Descriptive statistics such as frequencies, proportions, and cross tabulation were employed. The crude odds ratio (COR) and adjusted odds ratio (AOR) were calculated at 95 percent confidence intervals (CI) for binary and multivariable logistic regression to examine the strength of association between the outcome variable and independent factors. During bivariable analysis, variables having a p- value of less than 0.25 were chosen for multivariable logistic regression analysis, and variables having a p-value of less than 0.05 in multivariable analysis had significant associations with the dependent variable.

Ethical approval

Ethical clearance was obtained from the Ethics Review Committee of Debre Tabor University, Ethiopia with Ref NO/HP/713/01/2021 G.C. And then, the official letter was obtained from Debre Tabor Comprehensive Specialized Hospital for permission. All methods were carried out in accordance with relevant guidelines and regulations. The informed consent was obtained from all subjects and/or their legal guardian(s). The names and medical record identification numbers were not collected to keep the study participants' privacy.

Results

Socio-demographic and obstetric characteristics of the mother and preterm neonates

Out of 279 study participants, 267 were included in the study, with a completion rate of 95.7%. The mean age with standard deviation (SD) of the mother was 28.7 (6.9) years old. Nearly half (50.19%) of mothers were in the age group of 20–34 years. The majority (74.16% and 85.0%) of mothers were from urban areas and had spontaneous vaginal delivery.

From the total of mothers, 58.80%, 13.48%, and 15.73% of mothers had RH (Rhesus) + ve, Antepartum Hemorrhage (APH), and Premature rupture of membranes (PROM) respectively. Moreover, 13.48% and 18.35% of mothers had diabetes mellitus (DM), respectively. Of the total mothers included in the study, 83.15% of them had ante-natal care (ANC). Of these, 74.91% of mothers had had at least four ANC follow-ups.

From the total of preterm neonates included in the study, 52.43% and 76.78% were male and had a birth weight of >  = 1500 g, respectively, during the study period. The majority of preterm neonates, 85.02%, were initiated by breastfeeding for one hour, and 83.52% had a 5th minute Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score of greater than 7. During the study period, 26.97%, 17.60%, 10.86%, and 10.11% of preterm neonates had hypothermia, sepsis, birth asphyxia, and seizures, respectively (Table 1).

Table 1 Sociodemographic and obstetric characteristics of mothers and preterm neonates at Debre Tabor Comprehensive Specialized Hospital, Ethiopia, in 2021.
Full size table

The proportion of hypoglycemia

In this study, the proportion of hypoglycemia was found to be 23.59% (95% CI 18.9–29.1). Moreover, 49 (18.35%) of preterm neonates died during the study period.

Associated factors of hypoglycemia

Both bi-variable and multivariable logistic regression was computed. In binary logistic regression, variable including PROM, maternal diabetes, preeclampsia, sex of neonates, birth weight, initiation of breastfeeding, 5th min APGAR score, hypothermia, sepsis, birth asphyxia, and seizure were having a p- value of less than 0.25 at 95% CI with hypoglycemia. Whereas, in multivariable analysis, variable including maternal diabetes, hypothermia, birth asphyxia, and seizure were having a p-value of less than 0.05 at 95% CI, which had statistically significant associations with hypoglycemia.

In this study, preterm neonates with hypothermia were 4.5 times more likely to develop hypoglycemia than preterm neonates without hypothermia (AOR = 4.5; 95 CI 3.4, 7.2). Likewise, preterm neonates with birth asphyxia were 5.1 times more likely to develop hypoglycemia than preterm neonates without birth asphyxia (AOR = 5.1; 95 CI 3.9, 27.1). Preterm neonates who had seizure were 4.7 times more likely to develop hypoglycemia than preterm neonates who had no seizure (AOR = 4.7; 95 CI 2.8, 17.8). Preterm neonates born of diabetic mothers were 6.7 times more likely to develop hypoglycemia than preterm neonates born without a diabetic mother (AOR = 6.7; 95 CI 3.3, 27.2) (Table 2).

Table 2 Associated factors of hypoglycemia at Debre Tabor Comprehensive Specialized Hospital, Ethiopia, in 2021.
Full size table

Discussion

The proportion of hypoglycemia and associated factors among preterm neonates admitted to the neonatal Intensive Care Unit at Debre Tabor Comprehensive Specialized Hospital, Northcentral, Ethiopia was found to be 23.59% (95% CI 18.9–29.1). Furthermore, hypothermia, birth asphyxia, seizure, and neonates born to diabetic mothers were discovered to be risk factors for hypoglycemia.

This finding is consistent with another study conducted in Nigeria, which found that 28.3%26, and Ethiopia, 25%8. However, the finding is higher than the study conducted in Israel22, in Kenyatta National Hospital 14.7%27, in Tehran hospital 15.15%28, in India 21.2%29, and Uganda 2.2%3.

These differences may have been due to variations in the sampling size, study period, setting, and study design. Moreover, the level of the healthcare system regarding the detection and treatment of hypoglycemia is often different between developed and resource-limited countries or continents30,31. In this regard, the study was conducted in a level II neonatal intensive care unit with limited equipment or materials to support sick neonates and also limited opportunities for updated and advanced training to improve quality, which may increase the rate of neonatal hypoglycemia in the study area as compared with another study setting.

The odds of hypoglycemia among preterm neonates with hypothermia were 4.5 times higher as compared to preterm neonates without hypothermia. When a baby gets cold, he or she uses up more glycogen to keep warm, and then they must use their glucose stores to keep warm, which causes blood sugar to drop and the baby to become hypothermic, as well as hypoglycemic32,33. As a result, preventing and managing hypothermia through warm chains and skin-to-skin care is critical to avoid hypoglycemia and its associated complications23,34.

The odds of hypoglycemia among preterm neonates with birth asphyxia were 5.1 times higher as compared to a preterm with no birth asphyxia. Because anaerobic metabolism is used to maintain blood glucose concentrations in the neonatal period, birth asphyxia increases the risk of hyperinsulinism35,36. Prevention and treatment of birth asphyxia by trained and skilled healthcare providers is critical for every birth neonate, regardless of the cause, in order to avoid hypoglycemia and improve survival rates37,38.

The odds of hypoglycemia in preterm neonates with seizures were 4.7 times higher than in preterm neonates without seizures. This can result in altered glucose metabolism, the reduction of intracellular energy metabolites and phosphocreatine, and the accumulation of metabolic intermediates, such as lactate and adenosine, which result in neonatal hypoglycemia39. Thus, diagnosing and managing neonatal seizures is essential to improving the survival of neonates. The odds of hypoglycemia among preterm neonates born to diabetes mothers were 6.7 times higher as compared to preterm neonates born to non-diabetic mothers. Maternal diabetes is one of the major problems in neonates following a pregnancy complicated by diabetes. Another is hypoglycemia. Because glucose freely crosses the placenta, maternal hyperglycemia associated with GDM causes elevated glucose levels in the fetus, resulting in hyperinsulinism40,41. Thus, frequent monitoring and evaluation of glucose levels among delivered mothers is crucial worldwide in general and in the study area in particular to reduce the burden of hypoglycemia in neonates42,43.

Although this study attempted to explore hypoglycemia and its associated factors for the first time in the study, it has some limitations. Firstly, it was a cross-sectional study; it’s a snapshot, which is fronting for a chicken-egg dilemma, and secondly, the study was conducted in a single setting, Hence, risk validation and development model, randomized control trials, and/or cohort studies are recommended to better realize the detection rate of hypoglycemia and associated factors among neonates.

Conclusion

The proportion of hypoglycemia and associated factors among preterm neonates admitted to the neonatal intensive care unit at Debre Tabor Comprehensive Specialized Hospital was found to be high. The associated factors for the occurrence of hypoglycemia were discovered to be neonates with hypothermia, birth asphyxia, seizure, and neonates born with a diabetes mother. Thus, recognizing and treating the above associated factors is essential to preventing, and controlling hypoglycemia.