|Year : 2011 | Volume
| Issue : 2 | Page : 53-58
Study of blood glucose level in normal and low birth weight newborns and impact of early breast feeding in a tertiary care centre
Arun Kumar De, Rupa Biswas, Moumita Samanta, Chanchal Kumar Kundu
Department of Pediatric Medicine, Medical College, Kolkata, India
|Date of Web Publication||17-Feb-2012|
Arun Kumar De
Anandalok Co-operative Housing Society Ltd, Flat No: 2/1, Premises No: 05-109, Plot No: BB-50, Action Area: I B, New Town Rajarhat, Kolkata-700 156
| Abstract|| |
Background and Objectives: Neonatal hypoglycemia, a common metabolic problem, often goes unnoticed owing to lack of specific symptoms. We designed this study to assess the incidence of hypoglycemia in healthy normal birth weight and low birth weight babies, including both preterm and small for gestational age (SGA) newborns, to evaluate the impact of early breastfeeding on hypoglycemia and to assess the impact of exclusive breast feeding on glucose values up to 48 h of age.
Design and Settings: A hospital-based prospective longitudinal study.
Materials and Methods: The study was conducted over six months involving one hundred fifty healthy (both term and preterm) appropriate for gestational age (AGA) or SGA babies with birth weight between 1.5 kg and 3.99 kg. Blood glucose values were measured at the age of 1 h, 6 h, 12 h, 24 h and 48 h after delivery which was independent of feeding time. Blood glucose value less than 40 mg/dl (2.2 mmol/l) was defined as hypoglycemia. Sick newborns, those less than 34 weeks of gestation or less than 1500 g, infant of diabetic mother, those with birth asphyxia, congenital malformations and endocrine deficiencies were excluded.
Results: Overall incidence of hypoglycemia was 32%. Hypoglycemia was significantly greater in SGA and preterm as compared to AGA and term newborns respectively (P<0.001). Incidence of hypoglycemia was significantly more in newborns with delayed breast feeding than early breast feeding (64% vs 17%; P<0.001).
Conclusion: Low birth weight babies (both preterm and small-for-date) are prone to develop hypoglycemia especially in first 24 h of life with delayed introduction of breast feeding being an additional risk.
Keywords: Appropriate for gestational age, early breast feeding, hypoglycemia, low birth weight, pre-term, small for gestational age
|How to cite this article:|
De AK, Biswas R, Samanta M, Kundu CK. Study of blood glucose level in normal and low birth weight newborns and impact of early breast feeding in a tertiary care centre. Ann Nigerian Med 2011;5:53-8
|How to cite this URL:|
De AK, Biswas R, Samanta M, Kundu CK. Study of blood glucose level in normal and low birth weight newborns and impact of early breast feeding in a tertiary care centre. Ann Nigerian Med [serial online] 2011 [cited 2015 Mar 4];5:53-8. Available from: http://www.anmjournal.com/text.asp?2011/5/2/53/92951
| Introduction|| |
Neonatal hypoglycemia is a common metabolic disease  due to inability to maintain glucose homeostasis. The overall prevalence depends on birth weight, gestational age and intrauterine growth retardation. Since quite a proportion of neonates do not manifest any symptoms despite existence of hypoglycemia, exact incidence is difficult to work out. In other words, symptomatic hypoglycemia is not common (1-3 per 1000 live births) as against chemical hypoglycemia [67% in preterm small for gestational age (SGA) to 4% in term appropriate for gestational age (AGA)].  Undiagnosed hypoglycemia can have long term neurological consequences; thus the emphasis is on prevention and early detection along with treatment of asymptomatic hypoglycemia. Prognosis of these newborns with hypoglycemia depends on how promptly and efficiently hypoglycemia is managed. The maintenance of normoglycemia in newborns depends upon adequacy of glycogen stores, maturation of glycogenolytic and gluconeogenic pathways and an integrated endocrine response.  The endocrine events believed to trigger the release of glucose and the metabolism of fat from peripheral stores is an increase in adrenaline secretion and rapid fall in insulin: glucagon ratio during the first few hours of life.  These endocrine changes increase the activities of the essential enzyme for glycogenolysis (release of glucose from stored glycogen in liver, cardiac muscles and brain), gluconeogenesis, lipolysis and ketogenesis, namely glycogen phosphorylase, phosphophenolpyruvate carboxykinase, lipoprotein lipase and hydroxymethylglutaryl-CoA synthase respectively. Usually the transition from intra-uterine glucose regulation to extra-uterine adaptation develops in first 24 h of age.  The definition of hypoglycemia in the newborn infant has remained controversial because of a lack of significant correlation among plasma glucose concentration, clinical symptoms and long-term sequelae.  The operational threshold for hypoglycemia is currently believed to be a blood glucose value of < 40 mg/ dl (plasma glucose < 45 mg/dl).  However, if the plasma glucose value is < 45 mg/dl (2.5 mmol/l) in a symptomatic infant, clinical interventions aimed to increase blood glucose are indicated and if it is < 36 mg/dl without any symptoms a close surveillance should be maintained and should be intervened if plasma glucose remains below this level or infants become symptomatic or level does not increase after feed. I.V. glucose infusion should be given when plasma glucose level is < 20-25 mg/dl (1.1-1.4 mmol/l).  The most effective method of preventing hypoglycemia is early breast feeding which is preferred to formula feeding. 
With this background, this study is done to identify the early onset asymptomatic hypoglycemia as soon as possible, to observe the impact of early breastfeeding on hypoglycemia and to evaluate the effect of exclusive breastfeeding on subsequent blood glucose values up to 48 h.
| Materials and Methods|| |
The "term" newborn is defined as those delivered between 37 completed weeks and 42 weeks of gestation and "preterm'' as born before 37 weeks of gestation. Birth weight is defined as normal birth weight (NBW) with weight between 2.5 kg and 3.9 kg, and LBW (low birth weight) with weight < 2.5 kg. The terms "AGA" and "SGA" were defined according to intrauterine growth curves based on percentile of birth weight.  All infants were exclusively breast-fed as per hospital policy (based on baby-friendly hospital policy). For infants delivered by cesarean section (CS), breastfeeding was started as soon as feasible and maximum within 4 h of delivery. Based on BFHI, 24 h rooming in and kangaroo mother care is practiced to encourage breast feeding. Newborns are separated from mother only in cases of maternal illness and until she is transferred to the ward. In these cases, formula feeds are given if mother remains unavailable beyond 4 h. Onset of breast feeding was recorded. 'Early feeding' is defined as initiation of breastfeeding within 2 h of delivery and 'delayed feeding' as initiation of breast feeding beyond 2 h of delivery. No prelacteal feeds were given.
It is a prospective longitudinal observational study. By observing the trends of deliveries conducted in our hospital over the past two years, we assumed 80% of newborns to be AGA and 20% to be SGA. Similarly, 80% were term and 20% preterm. Using a two-sided test for comparison of two independent samples, assuming an alpha of 0.05 and desired power of 0.99, the maximum sample size turned out for each group to be 21. Thus, one hundred and sixty six newborns that included both healthy both term and pre-term, AGA and SGA, between 1.5 and 3.9 kg body weight and beyond 34 weeks of gestation, delivered at the Eden Hospital, Calcutta Medical College during the period between January 2010 and June 2010, were selected prospectively by computer-generated random number table. Of these, three were infants of diabetic mother, four had birth asphyxia and two had congenital malformation. These nine newborns were excluded from the study population at the outset.
Capillary blood was collected by heel prick after proper aseptic measure for screening by reagent strips method and the same time venous blood sample was sent for laboratory confirmation by glucose oxidase method in an autoanalyzer. Blood glucose values were measured at the age of 1 h, 6 h, 12 h, 24 h and 48 h after delivery which was independent of feeding time. Blood glucose value less than 40 mg/dl (2.2 mmol/ l) was defined as hypoglycemia. Lethargy, jitteriness and seizures, tremor, apnea, poor feeding etc were considered to be clinical signs of hypoglycemia if they were unexplained by other diagnoses and corrected with the provision of glucose. Infants were considered as asymptomatic if low plasma glucose concentration was not associated with clinical signs. Infants found to have hypoglycemia were clinically re-examined, given an additional breast-feed and plasma glucose reassessed after 30 min. If plasma glucose remained below 2 mmol/l (36 mg/dl) despite additional feeding or infants became symptomatic, they were transferred to the neonatal intensive care unit for intervention and excluded from the study population. Five newborn developed early onset septicemia and two were later found to have hypoglycemia secondary to metabolic causes. Hence 150 newborns were involved in statistical analysis and formed the study group. Of these 150 study subjects, 108 were AGA and 42 SGA while 123 were term and 27 preterm. Thus the number of newborn in every group remained above 21 which is the minimum number to maintain a study power of 0.99.
The study proposal was approved by the Institutional Ethical Committee prior to the commencement of the study. During the study, ethical issues were dealt rigorously according to revised Helsinki 2000 protocol. Prior to enrollment in the present study, parents and responsible caregivers of the neonates were properly counseled in their own vernacular and a written informed consent was taken from them.
Data were presented in the form of statistical Tables and charts. SPSS software version 17 was used. Serum blood glucose values were expressed in terms of mean and S.D. Two sample t tests were used for validation of quantitative data. For the comparison of proportions ie, categorical variables Chi-square test was used. P<0.05 was considered as significant. By linear regression analysis, the effect of individual variables on hypoglycemia was assessed.
| Results|| |
One hundred and fifty neonates, including 108 AGA and 42 SGA, were involved in the study after fulfillment of the inclusion criteria. All newborns were recruited in the study at birth or 0 h of life. The median birth weight was 2540 (range 1600 - 3200 g), with a male to female ratio of 86:64 (1.34:1) and median gestational age of 38 weeks (range 33 - 41 weeks). 95 (63.33%) neonates were term AGA, 13 (8.66%) preterm AGA, 28 (18.66%) term SGA and 14 (9.33%) preterm SGA. Maximum number of the preterm babies were of low birth weight (96.29%) whereas the term low birth weight babies were only 28 in number (22.76%). Only one baby was preterm with normal birth weight. There was positive correlation between birth weight and gestational age (r = 0.65). 27 % (29/108) of AGA babies were born by CS; whereas 52 % (22/42) of SGA babies were born by CS. Rest were delivered vaginally. 100 newborns belong to early breast feeding group while rest 50 had delayed commencement of breast feeding.
Overall prevalence of hypoglycemia is 49 out of 150 newborns or 32.67%. Incidence of hypoglycemia is greater in LBW than NBW (64% versus 14% respectively) and SGA than AGA (64% versus 26% respectively; P<0.01) Preterm neonates had greater incidence of hypoglycemia than their term counterparts (77.77% versus 22.95% respectively; P<0.01)) [Table 1]. Maximum numbers of cases of hypoglycemia were seen within the first 24 h of age. Seventeen infants had low glucose concentration at 1 h, 33 infants at 6 h, and 12 infants at 12 h and none of infants had hypoglycemia at 24 h and 48 h of age. Mean blood glucose values of the LBW babies were significantly lower than that of the NBW babies at 1 h, 6 h, 12 h, 24 h and 48 h after delivery (P < 0.001 in the entire time schedule) [Table 2]. In similar observation, lower mean blood glucose values were found in SGA than AGA newborns (P< 0.001) [Table 2] and preterm than term neonates (P< 0.001 in the entire time schedule) [Table 3].
|Table 2: Blood glucose values [mean (mg/dl) +/- SD], P values and t values in LBW, NBW, AGA and SGA babies|
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|Table 3: Blood glucose values [mean (mg/dl) ± SD], P values and t values in preterm and term babies|
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Out of 50 delayed feeding group, 28 had hypoglycemia (56%) and out of 100 early feeding group, 21 (21%) had hypoglycemia (χ2 = 33.48, 'P'<0.001) [Table 1]. Mean blood glucose values in delayed feeding group were significantly lower than early feeding group (P< 0.001 in the entire time schedule) [Table 4]. Out of 23 'delayed feeding group' of LBW babies, 16 had hypoglycemia (69.56%). Out of 31 early feeding group of the same class, 19(61.29%) had hypoglycemia. 74% of newborn delivered by CS had hypoglycemia and of which 31.6% had delayed feeding and majority were preterm SGA newborns. By linear regression model, the regression coefficient or the effect of individual variables on hypoglycemia was determined. Coefficient of regression (R) of prematurity factor on hypoglycemia is 0.470, LBW 0.459, delayed feeding 0.627 and CS 0.614.
|Table 4: Blood glucose values [mean (mg/dl) ± SD], P values and t values in delayed and early feeding groups|
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| Discussion|| |
Hypoglycemia is not a disease but a symptom of other diseases or lack of metabolic adaptation postnatally. Manifestations of hypoglycemia are non-specific but unexplained by other diagnoses and corrected with the provision of glucose. However, when the low blood glucose levels are prolonged or recurrent, they may result in acute systemic effects and neurologic sequelae. According to AAP guideline 2011,  there has been no substantial evidence-based progress in defining what constitutes clinically important [neonatal hypoglycemia (NH)], particularly regarding how it relates to brain injury, and that monitoring for, preventing and treating NH remain largely empirical. The guidelines call for immediate intravenous glucose for infant who are symptomatic and have glucose levels lower than 40 mg/dl. For asymptomatic at-risk infants, the initial feed should be given within 1 h of birth, with glucose screening 30 min after the first feed. Because there is no point-of-care screening method reliable enough to be used as the sole method for screening for NH, the blood or plasma glucose concentration must be confirmed by laboratory testing done simultaneously. In our study too, besides doing the reagent strip test, blood was sent for laboratory measurement of glucose immediately. However, therapy required was initiated based on reagent strip test itself.
In our study, we found that overall incidence of hypoglycemia in healthy breastfed newborns was 32% and the blood glucose values increased as their hours of life increased. Maximum numbers of cases of hypoglycemia were seen within the first 24 h of age. Seventeen infants had low glucose concentration at 1 h, 33 infants at 6 h, and 12 infants at 12 h and none of infants had hypoglycemia at 24 h and 48 h of age. A similar observation was made by Hoseth et al.,  in the breast-fed term AGA infants. They found that blood glucose concentrations within the first 24 h of delivery were significantly lower than those after 24 h. Bhat et al.,  also found that greater episodes of hypoglycemia (98%) occurred in the first 24 h of life in SGA newborns. Plasma insulin/glucose ratio was significantly higher in hypoglycemic than non-hypoglycemic babies, whereas the cortisol levels were similar. The hypoglycemic babies were more likely to be sick and oral feeds had been initiated by 1 h of life in only 37% of them compared to 63% of non-hypoglycemic babies. Based on meta-analysis (studies published 1986 to 1994) of low plasma glucose thresholds in full-term normal newborns, the authors specifically noted that given the lower plasma glucose levels in normal breast-fed infants, the low threshold for exclusively breast-fed infants might even be lower. Recommendation based on this threshold approach was a blood glucose value of 28 mg/dl at 1-2 h after birth, 40 mg/dl at 3-47 h and 48 mg/dl at 48-72 h of life. 
Our study demonstrated significantly greater incidence of hypoglycemia in LBW newborn than NBW ones [Table 1]. The mean blood glucose values in the LBW newborns were significantly lower than that of the NBW newborns at 1 h, 6 h, 12 h, 24 h and 48 h after delivery, which is well correlated with the findings of Singhal et al.,  Anderson et al.,  conducted a cross-sectional study on 226 term uncomplicated newborns. Hypoglycemia is defined as a blood glucose value < 2.6 mmol/l during the 50 h of life. Overall incidence was 38% which was slightly higher than the present study. It may be due to higher cut-off value of hypoglycemia (2.6 mmol/l) in comparison to present study. Incidence of hypoglycemia in LBW was 55% which was slightly lower than the present study; it may be due to large number of LBW samples in the present study.
In the present study, significantly lower mean blood glucose values and higher incidence of hypoglycemia was found in SGA than the AGA babies [Table 1] and [Table 2]. Holtrop PC  studied the incidence of hypoglycemia in the large for gestational age (LGA) and the SGA babies. Definition of hypoglycemia chosen was that suggested by Srinivasan et al. Hypoglycemia was detected in 14.7% of SGA babies which was much lower than that of the present study. Higher incidence in the present study may be due to large number of the LBW infants present in the SGA group which is also a contributing factor of hypoglycemia.
Bhat et al.,  found hypoglycemia in 25.2% of SGA babies as compared to 32.8% reported by Lubchenco and Bard.  The variability in incidence could be partly due to different definitions used for hypoglycemia, SGA and different policies of feeding.
Besides suffering from greater incidence of hypoglycemia (preterm vs term being 77.77% vs 22.95%), the mean blood glucose values in the preterm babies were significantly lower than that of the 'term' babies [Table 2] and [Table 4]. Similar findings were reported by other workers. ,, Hawdon et al.,  quoted the incidence of hypoglycemia in the term babies ranging between 0 and 8% and between 3 and 15% in the preterm babies. Higher number of hypoglycemia in the preterm babies is probably due to very low mean birth weight in the preterm babies, immaturity of the glycogenolytic and gluconeogenesis enzymes and delayed onset of feeding.
Maximum numbers of cases of hypoglycemia were seen within the first 24 h of age especially at 6 h of age. Hewitt in 2005  also found the lowest blood glucose levels <25mg/dl at 3-6 h of age after systematic analysis of breastfed term infants. Findings in our study can be partly explained by the fact that most of the preterm SGA had hypoglycemia and it is known that establishment of enteral feeds is essential for metabolic adaptation from intrauterine continuous nutrient supply to extrauterine intermittent supply of nutrients. This adaptation is delayed in preterm SGA including delayed induction of gluconeogenetic enzymes resulting in the nadir of glucose at 6 h of life. Mean blood glucose values in delayed feeding group were significantly lower than that in early feeding group in the LBW infants. There was also significant difference in blood glucose values between early and delayed feeding group of the NBW babies. But the mean blood glucose values in NBW babies were higher than that of LBW babies in both early and delayed feeding group [Table 4]. While 56% of newborns developed hypoglycemia in delayed feeding group, only 21% in early feeding group had hypoglycemia [Table 1]. Sasidharan et al.,  in a hospital-based prospective study concluded that hypoglycemia was a common problem in apparently normal asymptomatic babies. Of the eight variables that independently and strongly predicted the risk of neonatal hypoglycemia, prematurity, low birth weight, infant of diabetic mother, maternal oligohydramnios and a breastfeeding delay of more than 2 h after delivery are few to mention. Mandatory blood glucose screening in babies with any of the risk factors serves as an easy and cost-effective measure for the prompt identification of this condition. WHO, the AAP and the National child birth trust of the United Kingdom recommends that early and exclusive breastfeeding is safe to meet the nutritional needs of healthy term infants and healthy full-term infants to do not develop symptomatic hypoglycemia, which is implied as a result of under feeding.  Thus routine screening for hypoglycemia is not necessary in healthy term AGA infants and should be done in infants with risk factors for hypoglycemia.
| Conclusion|| |
The study depicts how common hypoglycemia and factors influencing it is of clinical significance. This study highlights that infants should be breastfed immediately and frequently to prevent hypoglycemia and that LBW infants (both preterm and small-for-date) are at greater risk especially in first 24 h of life. Both these points are already known, but our study further confirms these findings. However, long-term prospective studies are needed to evaluate the future neurological damage in asymptomatic healthy term babies with hypoglycemia.
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[Table 1], [Table 2], [Table 3], [Table 4]