Hypoglycaemia is a common metabolic abnormality in neonates which is usually seen shortly after delivery [1]. During their transition from intrauterine to extra-uterine life, their plasma glucose concentrations usually decline in the first few hours of life. Failure of adaption mechanisms that will rise their glucose to the normal level due to different risk factors will result in hypoglycaemia [2]. There is an ongoing controversy about the definition of hypoglycaemia regarding blood glucose measurements [4–7]. In this study, a blood glucose level less than 47 mg/dl was considered hypoglycaemia for any postnatal or gestational age.
As there are few reports on neonatal hypoglycaemia in developing countries like Ethiopia [14–18], we evaluated transient neonatal hypoglycaemia which is seen in the first 48 hours [22] and its association with maternal, obstetric and neonatal factors in a tertiary care hospital setting from a developing country. In this study we found prevalence of hypoglycaemia in 25% of the neonates. Our finding is slightly lower than the study done in Nigeria in 2008 which was 28% [14] but it was similar with the report from Kenyatta National hospital which showed around 23.2% prevalence [15]. Unlike our finding, the study done on high risk neonates with SGA, IDM, preterm and other factors by Deborah L et al showed a prevalence of 51% which is higher than the current study [23].
Our study showed higher prevalence compared to a previous study done in Ethiopia at Tikur Anbessa hospital [18] and Tehran hospital [16] which was 14.89% and 15%, respectively. In these two studies they took a lower cut of point to consider hypoglycaemia (40 mg/dl and 35 mg/dl, respectively). In addition in the Tehran hospital study, the neonates were of age less than 3 hours, which can explain the difference from the current study [16]. Another study by Ruben et al [24] showed a 12% prevalence of hypoglycaemia in neonates in the first three hours of age. This can explain the lower prevalence compared to the current study which was done in the first 48 hours of age.
Several risk factors have been identified for neonatal hypoglycaemia including prematurity, SGA, postmaturity, multiple gestation, maternal toxaemia, perinatal asphyxia, hypothermia, sepsis, IDM, neonates who underwent exchange transfusion and delayed initiation of feeding. Neonates who are LGA, polycythemic are also at risk of developing hypoglycaemia [4, 8, 9].
In this study we found birth weight less than 2500 gm to be the most significant variable associated with neonatal hypoglycaemia. LBW neonates had a twofold increased risk and VLBW neonates had a fourfold increase in the risk of hypoglycaemia. Similar results were seen in a study conducted in south India and they found low birth weight to be an independent predictor of the risk of hypoglycaemia [17]. In contrast to our findings, a report from Nepal did not find low birth weight to be significantly associated with hypoglycaemia after adjusting for confounders [25].
Another factor which was found to be significantly associated with hypoglycaemia after multivariate analysis was hypothermia. The association between hypothermia and hypoglycaemia is widely described in different studies [26–28]. Hypothermia increases the risk of hypoglycaemia by increasing their glucose requirement [8, 9]. In our study, neonates with moderate to severe hypothermia had a considerable increase in the risk of hypoglycaemia. Comparable results were also seen in previous studies done by Sasidharan et al in 2002 who examined the risk factors for neonatal hypoglycemia in 605 neonates. In their series, a significant proportion of hypoglycaemic neonates were hypothermic at the time of sampling. They also found hypothermia to be significantly associated with hypoglycaemia after adjusting for confounders [17]. On the contrary, a cross sectional study conducted in Nepal on 578 neonates aged 0-48hrs, did not identify hypothermia as a significant risk factor for hypoglycaemia [25].
Our study found neonates born to mothers in the age range of 20-35yrs were less likely to develop hypoglycaemia. In contrary to our finding, a matched case control study was conducted in Allentown on term, non-diabetic pregnancies and they found maternal age was not significantly associated with neonatal hypoglycaemia [29]. The association of maternal age seen in our study could be due to a significant portion (84.2%) of the participant’s mothers falling in this age range.
The results of our study did not show a statistically significant difference in some factors that prior studies have identified as predictors of risk, such as maternal DM, mode of delivery, gestational age, small for gestational age, polycythemia, perinatal asphyxia and pregnancy induced hypertension [26, 27, 28, 30, 31]. Evaluating the association of maternal DM and neonatal hypoglycaemia was not feasible in our study since there were only two neonates born to diabetic mothers from the participants. Unlike our study, Ruben et al and colleagues conducted a cross sectional study on 4000 neonates to determine the true incidence of early neonatal hypoglycaemia and to confirm potential risk factors. They found gestational age to have the strongest association with hypoglycaemia [24]. Another study done in south India showed prematurity, maternal pre-ecclamsia and ecclampsia and birth asphyxia independently predicted the risk of neonatal hypoglycaemia [17]. This is in contrast to our investigation, in which none of these factors seem to influence the odds of hypoglycaemia. In a study from Nepal they found an independent association between polycytemia and hypoglycaemia [25]. This result was not replicated in our study. This could be attributed to the very small number of patients with polycythemia included in our study.
We did not find parity of the mother and prolonged rupture of membranes to be significantly associated with hypoglycaemia. Comparable results were seen in a prospective study from south India. Their data did not show significant difference in the incidence of hypoglycaemia between infants born to primipara and multipara mothers. Prolonged rupture of membrane also did not influence the risk of hypoglycaemia in their study [17].
Mode of delivery and small for gestational age were also not found to be significant predictors of neonatal hypoglycaemia in our study. Similar result was also seen in a cross sectional study conducted at a tertiary medical centre in Israel in 2014. They found small for gestational age was not associated with hypoglycaemia in the neonates [24].
In our study early feeding initiation was found to be protective in 6.8% of the neonates. However, delayed feeding initiation and whether the neonates were started on breast milk or mixed feeding was not associated with neonatal hypoglycaemia. Similar result was reported from Nepal [25] where they found no correlation between feeding delay and the risk of hypoglycaemia. On the contrary, in the study conducted in Kerala they found delay in initiation of feeding for more than 2hrs postnatal to be an independent predictor of the risk of neonatal hypoglycaemia [17].
In summary, our study found the prevalence of neonatal hypoglycaemia to be 25% in the first 48hrs of life as reported in other studies showing its burden. Low birth weight and the presence of moderate to severe hypothermia contribute considerably to the risk of hypoglycaemia. We found these two factors to be the strongest predictors of hypoglycaemia in these neonates. Neonates diagnosed to have RDS are also at an increased risk to develop hypoglycaemia. Moreover, initiation of feeding in the first 3hrs of life has been found to be a protective factor. Neonates delivered after prolonged duration of labor beyond 24hrs and those born to mothers in the age range of 20–35 year were also less likely to develop hypoglycaemia. These findings call for the need for early detection of hypoglycaemia and timely interventions such as early initiation of feeding and prevention of hypothermia.Therefore, looking for predisposing factors, taking timely preventive measures and early treatment of hypoglycemia is crucial to save neonates from acute complications, long term neurological abnormalities and mortality.