The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism

Muukkonen, Liisa; Männistö, Jonna M E; Jääskeläinen, Jarmo; Hannonen, Riitta; Huopio, Hanna

doi:10.1111/dmcn.14039

Cited by 29 publications

(27 citation statements)

References 22 publications

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“…In our cohort, adverse neurodevelopmental outcome was observed in 50% of patients with persistent CHI and 13.5% of children with transient CHI, respectively. This result is in line with other studies reporting neurodevelopmental sequelae in 25%-48% of patients with persistent CHI (13)(14)(15)(16)(17)(18)(19)21). Data concerning the outcome after transient CHI are still limited.…”

Section: Discussionsupporting

confidence: 91%

“…The prevalence of neurodevelopmental sequelae is reported to be up to 48% in patients with persistent CHI and 30% in children with transient CHI, respectively (13,14). However, two recent studies indicate that the prevalence of brain injury is similar in children with transient and persistent CHI (12,15). Furthermore, no significant improvement of the neurodevelopmental outcome can be seen over the last decades despite advances in treatment options (13,14,16,17).…”

Section: Introductionmentioning

confidence: 99%

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Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism

et al. 2020

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ObjectiveAim was to identify hypotheses why adverse neurodevelopment still occurs in children with transient or persistent hyperinsulinism despite improvements in long-term treatment options during the last decades.Material and MethodsA retrospective review of 87 children with transient (n=37) or persistent congenital hyperinsulinism (CHI) (n=50) was conducted at the University Children’s Hospital Duesseldorf, Germany. Possible risk factors for neurodevelopmental sequelae due to hypoglycemia were analyzed with a focus on the first days after onset of disease.ResultsMedian age at follow-up was 7 years (IQR 8). Adverse neurodevelopmental outcome was seen in 34.5% (n=30) of all CHI patients. Fifteen had mildly abnormal neurodevelopment and 15 had a severe hypoglycemic brain injury. In univariate analysis, mildly abnormal neurodevelopment was associated with the diagnosis of persistent CHI (odds ratio (OR) 8.3; p=0.004) and higher birth weight (mean difference 1049 g; p<0.001). Severe hypoglycemic brain injury was associated with the diagnosis of persistent CHI (OR 5.1; p=0.013), being born abroad (OR 18.3; p<0.001) or in a lower-level maternity hospital (OR 4.8; p=0.039), and of note history of hypoglycemic seizures (OR 13.0; p=<0.001), and a delay between first symptoms of hypoglycemia and first blood glucose measurement/initiation of treatment (OR 10.7; p<0.001). Children with severe hypoglycemic brain injury had lower recorded blood glucose (mean difference -8.34 mg/dl; p=0.022) and higher birth weight than children with normal development (mean difference 829 g; p=0.012). In multivariate binary logistic regression models, lowest blood glucose <20 mg/dl (OR 134.3; p=0.004), a delay between initial symptoms and first blood glucose measurement/initiation of treatment (OR 71.7; p=0.017) and hypoglycemic seizures (OR 12.9; p=0.008) were positively correlated with severe brain injury. Analysis showed that the odds for brain injury decreased by 15% (OR 0.85; p=0.035) if the blood glucose increased by one unit.ConclusionWhile some risk factors for adverse outcome in CHI are not influenceable, others like lowest recorded blood glucose values <20 mg/dl, hypoglycemic seizures, and insufficiently—or even untreated hypoglycemia can be avoided. Future guidelines for management of neonatal hypoglycemia should address this by ensuring early identification and immediate treatment with appropriate escalation steps.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism

et al. 2020

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“…Early diagnosis of hypoglycaemia and appropriate treatment is essential to prevent neuroglycopenic brain damage (3,5). This holds particularly true for patients with syndromic HH, as these children may already have an increased risk of seizures and mental retardation (9).…”

Section: Discussionmentioning

confidence: 99%

“…Recurrent hypoglycaemic insults to the developing brain are associated with serious lifelong complications such as permanent brain injury and seizures (3,4,5). Therefore, early recognition and treatment of HH is the cornerstone for improving neurodevelopmental outcomes (6).…”

Section: Introductionmentioning

confidence: 99%

Persistent hyperinsulinaemic hypoglycaemia in children with Rubinstein–Taybi syndrome

Welters

El-Khairi

Dastamani

et al. 2019

European Journal of Endocrinology

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Objective Genetic aetiology remains unknown in up to 50% of patients with persistent hyperinsulinaemic hypoglycaemia (HH). Several syndromes are associated with HH. We report Rubinstein–Taybi syndrome (RSTS) as one of the possible causes of persistent HH. Early diagnosis and treatment of HH is crucial to prevent hypoglycaemic brain injury. Design Four RSTS patients with HH were retrospectively analysed. Methods Genetic investigations included next-generation sequencing-based gene panels and exome sequencing. Clinical characteristics, metabolic profile during hypoglycaemia and treatment were reviewed. Results Disease-related EP300 or CREBBP variants were found in all patients, no pathogenic variants were found in a panel of genes associated with non-syndromic HH. Two patients had classic manifestations of RSTS, three had choanal atresia or stenosis. Diagnosis of HH varied from 1 day to 18 months of age. One patient was unresponsive to treatment with diazoxide, octreotide and nifedipine, but responded to sirolimus. All required gastrostomy feeding. Conclusions Given the rarity of RSTS (1:125 000) and HH (1:50 000), our observations indicate an association between these two conditions. We therefore recommend that clinicians should be vigilant in screening for HH in symptomatic infants with RSTS. In children with an apparent syndromic form of HH, RSTS should be considered in the differential diagnosis.

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“…The incidence of adverse neurodevelopmental outcomes in patients with HI has been significant -varying between 26 and 44% in large patient groups, and has remained static over the last two decades despite advances in diagnosis and management [4,[6][7][8]. Poor neurological outcomes have also been found in transient HI patients and do not differ in incidence when compared to patients with persistent HI [9,10]. Long-term conservative management of HI has been shown to be associated with the remission of clinical symptoms by several groups [5,8,11] with the mean time to resolution on diazoxide treatment reported to be 4.8 years [12].…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia

Worth

Hashmi

Yau

et al. 2020

Orphanet J Rare Dis

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Background: Hypoglycaemia due to hyperinsulinism (HI) is the commonest cause of severe, recurrent hypoglycaemia in childhood. Cohort outcomes of HI remain to be described and whilst previous follow up studies have focused on neurodevelopmental outcomes, there is no information available on feeding and auxology. Aim: We aimed to describe HI outcomes for auxology, medications, feeding and neurodevelopmental in a cohort up to age 5 years. Method: We reviewed medical records for all patients with confirmed HI over a three-year period in a single centre to derive a longitudinal dataset. Results: Seventy patients were recruited to the study. Mean weight at birth was − 1.0 standard deviation scores (SDS) for age and sex, while mean height at 3 months was − 1.5 SDS. Both weight and height trended to the population median over the follow up period. Feeding difficulties were noted in 17% of patients at 3 months and this reduced to 3% by 5 years. At age 5 years, 11 patients (15%) had neurodevelopmental delay and of these only one was severe. Resolution of disease was predicted by lower maximum early diazoxide dose (p = 0.007) and being born SGA (p = 0.009). Conclusion: In a three-year cohort of HI patients followed up for 5 years, in spite of feeding difficulties and carbohydrate loading in early life, auxology parameters are normal in follow up. A lower than expected rate of neurodevelopmental delay could be attributed to prompt early treatment.

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The effect of hypoglycaemia on neurocognitive outcome in children and adolescents with transient or persistent congenital hyperinsulinism

Cited by 29 publications

References 22 publications

Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism

Risk Factors for Adverse Neurodevelopment in Transient or Persistent Congenital Hyperinsulinism

Persistent hyperinsulinaemic hypoglycaemia in children with Rubinstein–Taybi syndrome

Longitudinal Auxological recovery in a cohort of children with Hyperinsulinaemic Hypoglycaemia

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