Umbilical Cord Glucose: A Novel Screening Method for Congenital Hyperinsulinism to Prevent Brain Damage
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 50
- 主要终点
- Diagnostic performance of arterial umbilical cord blood glucose (UCBG) screening for pathological neonatal hyperinsulinism
研究概览
简要总结
Congenital hyperinsulinism (HI) causes persistent neonatal hypoglycemia that, if untreated, can lead to neurodevelopmental impairments (NDI) such as cognitive delays, cerebral palsy, epilepsy, and blindness. Despite being preventable with early diagnosis and treatment, 30-50% of affected infants still suffer NDI. Transient HI occurs in about 1 in 1,200 births, while persistent forms are rarer. Current screening focuses on high-risk groups but misses many infants with HI, resulting in delayed diagnosis and brain injury. Our pilot research suggests that measuring umbilical cord blood glucose (UCBG), already routinely collected for other purposes, can serve as a timely, non-invasive screening test for HI. Arterial UCBG below 3.5 mmol/L showed excellent accuracy in predicting pathological HI. This project aims to validate UCBG screening for neonatal HI, implement a national screening program, and assess the neurological outcomes of screen-positive infants. Planned studies:
- A review will analyze current screening strategies and the impact of delayed diagnosis on brain outcomes
- A nationwide, prospective study in Denmark will implement UCBG screening in all newborns. Infants with arterial UCBG below 3.5 mmol/L will undergo hypoglycemia monitoring and diagnostic testing. Diagnostic accuracy and optimal thresholds will be evaluated.
- Neurological follow-up at 6 months will assess development using standardized cognitive and motor tests, EEG, and MRI.
- A retrospective observational study to investigate whether UCBG can provide improved risk stratification for hypoglycaemia in infants born to mothers with diabetes.
详细描述
Although preventable with earliest possible diagnosis and treatment, the frequency of neurodevelopmental impairment (NDI; brain damage) in congenital hyperinsulinism (HI) still reaches 30-50%, including delayed psychomotor development, cognitive impairment, cerebral palsy, epilepsy and blindness. The incidence of transient HI ("perinatal stress hyperinsulinism") has been estimated to 1:1,200, whereas persistent HI occurs in 1:10,000 to 1;40,000. Both transient and persistent hyperinsulinism, here together named pathological HI, impose, unfortunately, a high risk of NDI if not promptly diagnosed and treated.
According to the classical WHO consensus, an ideal universal screening should be performed with a suitable test to diagnose a condition early enough to institute an effective treatment. Moreover, the screening must be specific, affordable, harmless, and worldwide applicable.
From a yet unpublished retrospective pilot study, a novel proposal has been established of how to implement timely screening by use of umbilical cord blood glucose (UCBG), which is already routinely measured in cord gas analysis for asphyxia, to predict neonatal HI. Until today, the use of UCBG screening for neonatal hypoglycemia is virtually a complete overlooked possibility, not only in Denmark, but internationally. In pilot study, reference intervals has been established for UCBG and showed that arterial (from the neonate to the placenta) UCBG below 3.5 mmol/L (65 mg/dL) had an excellent diagnostic performance in predicting pathological HI in the four included cases.
The overall aim of this study is to further develop this new and proposed ideal screening tool, in diagnosing neonatal pathological HI with the perspective of global implementation.
Research Plan Study 1 and 4 are not included in this description.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Screening
- 盲法
- None
入排标准
- 年龄范围
- — 至 8 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Live-born neonates delivered at participating Danish hospitals during the study period.
- •arterial umbilical cord blood glucose (UCBG) ≤3.5 mmol/L.
- •Written informed consent obtained from parent(s) or legal guardian(s).
- •Infants diagnosed with pathological neonatal hyperinsulinism (HI) following UCBG screening in Study
- •Written informed consent obtained from parent(s) or legal guardian(s) for participation in the follow-up study.
排除标准
- •No predefined clinical exclusion criteria.
- •Missing or unsuccessful arterial umbilical cord blood sampling resulting in an unavailable UCBG measurement.
- •Withdrawal of parental consent.
- •No predefined clinical exclusion criteria.
- •Withdrawal of parental consent.
研究组 & 干预措施
Arterial UCBG screen positive
Screen-positive infants will undergo two blood glucose measurements during the first hours after birth. Infants with a very low arterial UCBG (<2.5 mmol/L) will undergo a total of six glucose and G-BOBH measurements.
干预措施: For the screening, the interventions will be glucose measurements (and possibly G-BOBH), while follow-up assessments will include Bayley testing, EEG, and MRI. (Diagnostic Test)
结局指标
主要结局
Diagnostic performance of arterial umbilical cord blood glucose (UCBG) screening for pathological neonatal hyperinsulinism
时间窗: Birth to 72 hours of age
Diagnostic accuracy of arterial umbilical cord blood glucose (UCBG) measured at birth for identification of pathological neonatal hyperinsulinism using a predefined screening threshold of ≤3.5 mmol/L. Diagnostic accuracy will be summarized by the area under the receiver operating characteristic curve (AUC).
Neurodevelopmental outcome in infants diagnosed with pathological neonatal hyperinsulinism through UCBG screening
时间窗: Approx. 6 months of age
Presence of neurodevelopmental impairment at approximately 6 months of age, defined according to a prespecified composite assessment including Bayley-IV, EEG, and brain MRI findings.
次要结局
未报告次要终点