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Treatment of blood glucose concentrations in newborn babies
Comment
Treatment of blood glucose concentrations in newborn babies
www.thelancet.com Vol 382 December 21/28, 2013
given dextrose gel were less likely to be admitted to intensive care for hypoglycaemia than were those given placebo (16 [14%] vs 30 [25%]), less likely to receive formula feeds (median 7 [range 1–21] vs 10 [1–24] feeds), and less likely to be formula fed at 2 weeks (5 [4%] vs 15 [13%]). We congratulate Harris and colleagues for their study of such a difficult and controversial area. Further information was obtained by use of masked continuous glucose monitoring. This information was difficult to interpret because most episodes had been treated by the time the monitor had been initialised, and delays in treatment meant that a low glucose concentration had frequently resolved by the time the trial treatment was given, reducing the power of any secondary comparisons. For example, despite a halving of the duration of low interstitial glucose concentrations (from 164 min to 81 min) without rebound, this finding was not statistically significant. Further studies are needed to assess dose and frequency of use. Dextrose gel has been recommended before, roughly 20 years ago,5 but a previous randomised trial6 that was designed to assess intermittent blood glucose concentrations, rather than important functional outcomes, did not show differences between gel and placebo and remains unpublished. In view of the disconnect between blood glucose concentrations and symptoms, design for assessment of functional outcomes seems preferable. For most services, use of buccal dextrose, even as an emergency stopgap, has fallen into disuse. We now have
Published Online September 25, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61755-9 See Articles page 2077
BSIP/Corbis
Few subjects provoke such controversy as does the measurement of blood glucose concentration in an otherwise healthy newborn baby. Little evidence-based guidance is available to tell clinical staff what concentration of blood glucose should provoke intervention to raise concentrations and avoid potentially disastrous neurological complications.1 Indeed, whether a low concentration causes problems in the absence of symptoms is debatable. Over the years, various thresholds and strategies have evolved despite the fact that by itself a blood glucose measurement is an inadequate guide to assess the fundamental problem of neuroglycopaenia and its sequelae, except at extremely low values.2 Many babies are admitted to neonatal intensive-care units, separated from their mothers, and given an intravenous infusion of glucose, thus disrupting the establishment of breastfeeding. To minimise this drawback, individual neonatal services have evolved their own operational thresholds and subsequent management strategies that are based mainly on consensus and opinion. Most specialists agree that the existence of neurological symptoms in association with low glucose concentrations needs urgent action and investigation, and some degree of consensus exists about the babies at greatest risk3— broadly those from pregnancies complicated by maternal diabetes, obesity, low birthweight, restriction of fetal growth, overt pathological abnormalities producing hyperinsulinism, or babies with inborn errors of metabolism. Management beyond this group is much less clear and, in view of the low chance of long-term complications, clinical services need to act to minimise the effect of an abnormal screening result on neonatal adaptation and feeding. In The Lancet, Deborah Harris and colleagues’ randomised study4 assesses whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. The investigators also analyse the effect of the gel on key neonatal operational outcomes—admission to a neonatal intensive-care unit and later feeding strategies. The findings show that the gel reduced the frequency of treatment failure, the trial’s primary endpoint, compared with placebo (16 [14%] of 118 vs 29 [24%] of 119 babies; relative risk 0·57, 95% CI 0·33–0·98). Furthermore, babies
2045
Comment
high-quality evidence that it is of value and should be part of the response to triggering of treatment. With their study, Harris and colleagues have further contributed to our understanding of the prevalence and timing of low concentrations of blood sugar. In their previous analysis of risk groups acquired prospectively on the basis of birthweight, gestation, and maternal diabetes, the investigators showed that 51% had at least one low measurement, 19% had values of less than 2·0 mmol/L, and 19% had recurrent episodes.7 Furthermore, more than a third of episodes took place after three normal values and 6% of episodes after more than 24 h of birth. Despite the welcome results of Harris and coworkers’ present trial,4 we need further trials to refine our operational definitions. The popular definition of 2·6 mmol/L seems to be based on an extremely small number of newborn babies in a study of evoked cortical potentials and a retrospective assessment of long-term low values in a low birthweight feeding study, which is hardly robust evidence, and an exhortation to maintain generous normoglycaemia in newborn babies.8 Such trials can and should be randomised and include outcome evaluations to strengthen our understanding of the association between low blood glucose readings,
their timecourse, and neurological outcomes; indeed one strategy for doing this has been proposed.1 Until more information is available, practice will continue to be based on uncertain facts; however, use of buccal dextrose gel should help to minimise unnecessary interventions. Neil Marlow Neonatal Medicine, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK [email protected] I declare that I have no conflicts of interest. 1
2 3 4
5 6
7 8
Boluyt N, van Kempen A, Offringa M. Neurodevelopment after neonatal hypoglycemia: a systematic review and design of an optimal future study. Pediatrics 2006; 117: 2231–43. Boardman JP, Wusthoff CJ, Cowan FM. Hypoglycaemia and neonatal brain injury. Arch Dis Child Educ Pract Ed 2013; 98: 2–6. Rozance PJ, Hay WW Jr. Describing hypoglycemia—definition or operational threshold? Early Hum Dev 2010; 86: 275–80. Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial. Lancet 2013; published online Sept 25. http://dx.doi.org/10.1016/S0140-6736(13)61645-1. Bourchier D, Weston P, Heron P. Hypostop for neonatal hypoglycaemia. N Z Med J 1992; 105: 22. Troughton KEV, Corrigan NP, Tait RME. Hypostop gel in the treatment of neonatal hypoglycaemia: a randomised controlled trial. Arch Dis Child 2000; 82 (suppl 1): A30. Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161: 787–91. The Lancet. Brain damage and neonatal hypoglycaemia. Lancet 1989; 1: 882–83.
AJ Photo/Science Photo Library
Radiation induced bowel injury: a neglected problem
Published Online September 23, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61946-7 See Articles page 2084
2046
Stigma associated with radiation induced bowel injury (RBI) has restricted interest in its pathogenesis and the pathophysiological processes that occur as a consequence. This neglect has in turn hampered clinical management and led to the widely held belief that RBIs are not amenable to treatment. RBI is more common than Crohn’s disease, yet attracts a fraction of the research funding. Furthermore, only a fifth of patients with RBI in the UK see a gastroenterologist, and most who do so are managed ineffectively.1 In The Lancet, Jervoise Andreyev and colleagues1 report findings from one of the first randomised trials to show that the symptoms of RBI can be improved by a therapeutic intervention. In what will probably be viewed as a landmark trial, Andreyev and colleagues randomised 218 patients to three groups: algorithm-based treatment led by a gastroenterologist or nurse, or usual care. The findings show that in terms of the trial’s primary endpoint, the mean difference in change in score on the
IBDQ-B instrument between baseline and 6 months, both gastroenterologist-led care (5·47, 95% CI 1·14–9·81; p=0·01) and nurse-led care (4·12, 0·04–8·19; p=0·04) were superior to usual care; in other words, both men and women with a range of RBIs can have clinical and statistically significant improvements in their symptoms with tailored management programmes determined by an investigative and therapeutic algorithm. A reasonable question to ask is why a diagnostic and therapeutic algorithm should work in a group of disorders considered refractory to treatment, without the use of new pharmaceutical agents. The answer is surprisingly simple. The investigators recognised that RBI frequently affects several parts of the bowel and almost always affects several normal physiological processes adversely. The identification of these processes (using the diagnostic part of the algorithm) therefore enables adaptive measures, such as dietary modifications and the use of commonly prescribed drugs to reduce the severity www.thelancet.com Vol 382 December 21/28, 2013
Treatment of blood glucose concentrations in newborn babies
www.thelancet.com Vol 382 December 21/28, 2013
given dextrose gel were less likely to be admitted to intensive care for hypoglycaemia than were those given placebo (16 [14%] vs 30 [25%]), less likely to receive formula feeds (median 7 [range 1–21] vs 10 [1–24] feeds), and less likely to be formula fed at 2 weeks (5 [4%] vs 15 [13%]). We congratulate Harris and colleagues for their study of such a difficult and controversial area. Further information was obtained by use of masked continuous glucose monitoring. This information was difficult to interpret because most episodes had been treated by the time the monitor had been initialised, and delays in treatment meant that a low glucose concentration had frequently resolved by the time the trial treatment was given, reducing the power of any secondary comparisons. For example, despite a halving of the duration of low interstitial glucose concentrations (from 164 min to 81 min) without rebound, this finding was not statistically significant. Further studies are needed to assess dose and frequency of use. Dextrose gel has been recommended before, roughly 20 years ago,5 but a previous randomised trial6 that was designed to assess intermittent blood glucose concentrations, rather than important functional outcomes, did not show differences between gel and placebo and remains unpublished. In view of the disconnect between blood glucose concentrations and symptoms, design for assessment of functional outcomes seems preferable. For most services, use of buccal dextrose, even as an emergency stopgap, has fallen into disuse. We now have
Published Online September 25, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61755-9 See Articles page 2077
BSIP/Corbis
Few subjects provoke such controversy as does the measurement of blood glucose concentration in an otherwise healthy newborn baby. Little evidence-based guidance is available to tell clinical staff what concentration of blood glucose should provoke intervention to raise concentrations and avoid potentially disastrous neurological complications.1 Indeed, whether a low concentration causes problems in the absence of symptoms is debatable. Over the years, various thresholds and strategies have evolved despite the fact that by itself a blood glucose measurement is an inadequate guide to assess the fundamental problem of neuroglycopaenia and its sequelae, except at extremely low values.2 Many babies are admitted to neonatal intensive-care units, separated from their mothers, and given an intravenous infusion of glucose, thus disrupting the establishment of breastfeeding. To minimise this drawback, individual neonatal services have evolved their own operational thresholds and subsequent management strategies that are based mainly on consensus and opinion. Most specialists agree that the existence of neurological symptoms in association with low glucose concentrations needs urgent action and investigation, and some degree of consensus exists about the babies at greatest risk3— broadly those from pregnancies complicated by maternal diabetes, obesity, low birthweight, restriction of fetal growth, overt pathological abnormalities producing hyperinsulinism, or babies with inborn errors of metabolism. Management beyond this group is much less clear and, in view of the low chance of long-term complications, clinical services need to act to minimise the effect of an abnormal screening result on neonatal adaptation and feeding. In The Lancet, Deborah Harris and colleagues’ randomised study4 assesses whether treatment with dextrose gel was more effective than feeding alone for reversal of neonatal hypoglycaemia in at-risk babies. The investigators also analyse the effect of the gel on key neonatal operational outcomes—admission to a neonatal intensive-care unit and later feeding strategies. The findings show that the gel reduced the frequency of treatment failure, the trial’s primary endpoint, compared with placebo (16 [14%] of 118 vs 29 [24%] of 119 babies; relative risk 0·57, 95% CI 0·33–0·98). Furthermore, babies
2045
Comment
high-quality evidence that it is of value and should be part of the response to triggering of treatment. With their study, Harris and colleagues have further contributed to our understanding of the prevalence and timing of low concentrations of blood sugar. In their previous analysis of risk groups acquired prospectively on the basis of birthweight, gestation, and maternal diabetes, the investigators showed that 51% had at least one low measurement, 19% had values of less than 2·0 mmol/L, and 19% had recurrent episodes.7 Furthermore, more than a third of episodes took place after three normal values and 6% of episodes after more than 24 h of birth. Despite the welcome results of Harris and coworkers’ present trial,4 we need further trials to refine our operational definitions. The popular definition of 2·6 mmol/L seems to be based on an extremely small number of newborn babies in a study of evoked cortical potentials and a retrospective assessment of long-term low values in a low birthweight feeding study, which is hardly robust evidence, and an exhortation to maintain generous normoglycaemia in newborn babies.8 Such trials can and should be randomised and include outcome evaluations to strengthen our understanding of the association between low blood glucose readings,
their timecourse, and neurological outcomes; indeed one strategy for doing this has been proposed.1 Until more information is available, practice will continue to be based on uncertain facts; however, use of buccal dextrose gel should help to minimise unnecessary interventions. Neil Marlow Neonatal Medicine, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK [email protected] I declare that I have no conflicts of interest. 1
2 3 4
5 6
7 8
Boluyt N, van Kempen A, Offringa M. Neurodevelopment after neonatal hypoglycemia: a systematic review and design of an optimal future study. Pediatrics 2006; 117: 2231–43. Boardman JP, Wusthoff CJ, Cowan FM. Hypoglycaemia and neonatal brain injury. Arch Dis Child Educ Pract Ed 2013; 98: 2–6. Rozance PJ, Hay WW Jr. Describing hypoglycemia—definition or operational threshold? Early Hum Dev 2010; 86: 275–80. Harris DL, Weston PJ, Signal M, Chase JG, Harding JE. Dextrose gel for neonatal hypoglycaemia (the Sugar Babies Study): a randomised, double-blind, placebo-controlled trial. Lancet 2013; published online Sept 25. http://dx.doi.org/10.1016/S0140-6736(13)61645-1. Bourchier D, Weston P, Heron P. Hypostop for neonatal hypoglycaemia. N Z Med J 1992; 105: 22. Troughton KEV, Corrigan NP, Tait RME. Hypostop gel in the treatment of neonatal hypoglycaemia: a randomised controlled trial. Arch Dis Child 2000; 82 (suppl 1): A30. Harris DL, Weston PJ, Harding JE. Incidence of neonatal hypoglycemia in babies identified as at risk. J Pediatr 2012; 161: 787–91. The Lancet. Brain damage and neonatal hypoglycaemia. Lancet 1989; 1: 882–83.
AJ Photo/Science Photo Library
Radiation induced bowel injury: a neglected problem
Published Online September 23, 2013 http://dx.doi.org/10.1016/ S0140-6736(13)61946-7 See Articles page 2084
2046
Stigma associated with radiation induced bowel injury (RBI) has restricted interest in its pathogenesis and the pathophysiological processes that occur as a consequence. This neglect has in turn hampered clinical management and led to the widely held belief that RBIs are not amenable to treatment. RBI is more common than Crohn’s disease, yet attracts a fraction of the research funding. Furthermore, only a fifth of patients with RBI in the UK see a gastroenterologist, and most who do so are managed ineffectively.1 In The Lancet, Jervoise Andreyev and colleagues1 report findings from one of the first randomised trials to show that the symptoms of RBI can be improved by a therapeutic intervention. In what will probably be viewed as a landmark trial, Andreyev and colleagues randomised 218 patients to three groups: algorithm-based treatment led by a gastroenterologist or nurse, or usual care. The findings show that in terms of the trial’s primary endpoint, the mean difference in change in score on the
IBDQ-B instrument between baseline and 6 months, both gastroenterologist-led care (5·47, 95% CI 1·14–9·81; p=0·01) and nurse-led care (4·12, 0·04–8·19; p=0·04) were superior to usual care; in other words, both men and women with a range of RBIs can have clinical and statistically significant improvements in their symptoms with tailored management programmes determined by an investigative and therapeutic algorithm. A reasonable question to ask is why a diagnostic and therapeutic algorithm should work in a group of disorders considered refractory to treatment, without the use of new pharmaceutical agents. The answer is surprisingly simple. The investigators recognised that RBI frequently affects several parts of the bowel and almost always affects several normal physiological processes adversely. The identification of these processes (using the diagnostic part of the algorithm) therefore enables adaptive measures, such as dietary modifications and the use of commonly prescribed drugs to reduce the severity www.thelancet.com Vol 382 December 21/28, 2013