Maternal glycaemic control and risk of neonatal hypoglycaemia in Type 1 diabetes pregnancy: a secondary analysis of the CONCEPTT trial.

AIMS: To examine the relationship between maternal glycaemic control and risk of neonatal hypoglycaemia using conventional and continuous glucose monitoring metrics in the Continuous Glucose Monitoring in Type 1 Diabetes Pregnancy Trial (CONCEPTT) participants. METHODS: A secondary analysis of CONCEPTT involving 225 pregnant women and their liveborn infants. Antenatal glycaemia was assessed at 12, 24 and 34 weeks gestation. Intrapartum glycaemia was assessed by continuous glucose monitoring measures 24 hours prior to delivery. The primary outcome was neonatal hypoglycaemia defined as glucose concentration < 2.6 mmol/l and requiring intravenous dextrose. RESULTS: Neonatal hypoglycaemia occurred in 57/225 (25.3%) infants, 21 (15%) term and 36 (40%) preterm neonates. During the second and third trimesters, mothers of infants with neonatal hypoglycaemia had higher HbA1c [48 ± 7 (6.6 ± 0.6) vs. 45 ± 7 (6.2 ± 0.6); P = 0.0009 and 50 ± 7 (6.7 ± 0.6) vs. 46 ± 7 (6.3 ± 0.6); P = 0.0001] and lower continuous glucose monitoring time-in-range (46% vs. 53%; P = 0.004 and 60% vs. 66%; P = 0.03). Neonates with hypoglycaemia had higher cord blood C-peptide concentrations [1416 (834, 2757) vs. 662 (417, 1086) pmol/l; P < 0.00001], birthweight > 97.7th centile (63% vs. 34%; P < 0.0001) and skinfold thickness (P ≤ 0.02). Intrapartum continuous glucose monitoring was available for 33 participants, with no differences between mothers of neonates with and without hypoglycaemia. CONCLUSIONS: Modest increments in continuous glucose monitoring time-in-target (5-7% increase) during the second and third trimesters are associated with reduced risk for neonatal hypoglycaemia. While more intrapartum continuous glucose monitoring data are needed, the higher birthweight and skinfold measures associated with neonatal hypoglycaemia suggest that risk is related to fetal hyperinsulinemia preceding the immediate intrapartum period.

Validation of the continuous glucose monitoring sensor in preterm infants.

OBJECTIVE: Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. DESIGN: Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. SETTING: An international multicentre randomised controlled trial. PATIENTS: One hundred and eighty-eight very low birth weight control infants. OUTCOME MEASURES: Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. RESULTS: The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. CONCLUSIONS: CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.

Management of hyperglycaemia in the preterm infant.

In the fetus, the predominant energy supply is glucose transported across the placenta from the mother. As pregnancy progresses, the amount of glucose transported increases, with glycogen and fat stores being laid down, principally in the third trimester. In the well-term baby, there is hormonal and metabolic adaptation in the perinatal period to ensure adequate fuel supply to the brain and other vital organs after delivery, but in the preterm infant, abnormalities of glucose homeostasis are common. After initial hypoglycaemia, due to limited glycogen and fat stores, preterm babies often become hyperglycaemic because of a combination of insulin resistance and relative insulin deficiency. Hyperglycaemia is associated with increased morbidity and mortality in preterm infants, but what should be considered optimal glucose control, and how best to achieve it, has yet to be defined in these infants.

The continuous glucose monitoring sensor in neonatal intensive care.

OBJECTIVE: To determine the feasibility of continuous glucose monitoring in the very low birthweight baby requiring intensive care, as these infants are known to be at high risk of abnormalities of glucose control. METHOD: Sixteen babies were studied from within 24 hours of delivery and for up to seven days. RESULTS: The subcutaneous glucose sensors were well tolerated and readings were comparable to those on near patient whole blood monitoring devices. CONCLUSION: Continuous glucose monitoring is practical in neonates, giving detailed information about glucose control.

Pericardial effusion and cardiac tamponade as complications of neonatal long lines: are they really a problem?

AIM: To estimate the frequency of pericardial effusion/cardiac tamponade associated with the use of neonatal percutaneous long lines (PLLs) over the past five years. METHOD: A retrospective nationwide postal survey, of all neonatal and special care units in the United Kingdom. RESULTS: Eighty two cases of pericardial effusion/cardiac tamponade were reported from the five year period, during which we estimate that 46 000 PLLs were inserted. The calculated frequency of pericardial effusion/cardiac tamponade occurring with PLLs was 1.8/1000 lines. There were 30 deaths, giving a fatality rate after pericardial effusion of 0.7/1000 lines. CONCLUSIONS: Pericardial effusion/cardiac tamponade is a serious but infrequent complication of PLL use.

Neonatal group B streptococcal infection in South Bedfordshire, 1993-1998.

BACKGROUND: Group B streptococcus (GBS) is now the leading cause of neonatal bacterial sepsis in the western world. The incidence of GBS infection in the United States has been determined, and guidelines produced and implemented for the prevention of neonatal infection. Neither incidence nor guidelines are currently established in the United Kingdom. AIM: To define the pattern of neonatal infection within one hospital (Luton and Dunstable Hospital). METHOD: A six year retrospective analysis was performed. RESULT: An incidence of early onset GBS of 1.15 per 1000 deliveries, comparable with that documented in the United States, was found.

Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome.

Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.

Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions?

Neuronal intranuclear inclusions have been found in the brain of a transgenic mouse model of Huntington's disease and in necropsy brain tissue of patients with Huntington's disease. We suggest that neuronal intranuclear inclusions are the common neuropathology for all inherited diseases caused by expansion of polyglutamine repeats. We also suggest that patients with a pathological diagnosis of neuronal intranuclear hyaline inclusion disease may also have polyglutamine repeat expansions.

Renal length in sickle cell disease: observations from a cohort study.

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationships between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increased renal blood volume are likely contributors.

Renal length in sickle cell disease: observation from a cohort study

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationship between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increase renal blood volume are likely contributors.(AU)

Nerve growth factor selectively prevents excitotoxin induced degeneration of striatal cholinergic neurones.

Selective neuronal death is a prominent feature of human neurodegenerative disease both of genetic and idiopathic origin. Huntington's disease is characterised by the selective degeneration of striatal projection neurones, with the relative preservation of a variety of interneurones. The ability of the endogenous excitotoxin, quinolinic acid, to produce a pattern of selective neuronal cell death was investigated using immunocytochemical and histochemical techniques. We find that the large striatal, cholinergic interneurones are relatively spared, and that this sparing can be enhanced by the co-administration of the neurotrophin, nerve growth factor (NGF). Further, a single co-injection of NGF will selectively prevent both the cell death and morphological changes that occur within cholinergic cells when assessed 2 weeks later. These results suggest that an interaction between growth factors and excitotoxins can dramatically modify patterns of selective neuronal death.