血清脑红蛋白评估新生儿低血糖脑损伤的临床价值

目的探讨血清脑红蛋白（NGB）在新生儿低血糖脑损伤评估中的临床应用价值。方法选择100例低血糖新生儿为研究对象。根据振幅整合脑电图（aEEG）结果和/或临床表现，分为3组：症状性低血糖脑损伤组（n=22）、无症状性低血糖脑损伤组（n=37）和低血糖无脑损伤组（n=41）。比较各组患儿血糖、低血糖持续时间、NGB及神经元特异性烯醇化酶（NSE）水平、改良aEEG评分；分析NGB与NSE水平、改良aEEG评分之间的相关性并绘制受试者工作特征（ROC）曲线等。结果症状性低血糖脑损伤组血糖、改良aEEG评分低于无症状性低血糖脑损伤组及低血糖无脑损伤组（P < 0.05），NGB、NSE、低血糖持续时间高/长于无症状性低血糖脑损伤组及低血糖无脑损伤组（P < 0.05）。无症状低血糖脑损伤组血糖、改良aEEG评分低于低血糖无脑损伤组（P < 0.05），NGB、NSE及低血糖持续时间高/长于低血糖无脑损伤组（P < 0.05）。NGB与NSE、低血糖持续时间呈正相关（分别r=0.922、0.929，P < 0.05），与血糖、改良aEEG评分呈负相关（分别r=-0.849、-0.968，P < 0.05）；NGB、NSE、改良aEEG评分的ROC曲线下面积分别为0.894、0.890、0.941，NGB最佳截断值为108 mg/L，敏感度80.8%，特异度95.8%。结论血清NGB与NSE、改良aEEG评分比较，同样可作为评估低血糖新生儿脑损伤的特异性指标，具有一定的临床应用价值。     

早产儿血糖异常与脑损伤发生率的关系

目的探讨早产儿血糖异常与脑损伤发生率的关系。方法对138例早产儿分别于出生0 h、2 h、4 h、8 h、12 h、24 h进行血糖检测,血糖正常者入血糖正常组,血糖异常者分别入高、低血糖组,并于48 h、72 h继续监测血糖变化,血糖正常组若发生血糖波动及时调整组别。观测血糖异常持续时间,依据血糖异常时间分为0～6 h组,>6～<24 h组,≥24 h组。采用足跟血,应用ACCU-CHEK罗氏血糖仪进行血糖测定。出生7 d行颅脑CT或MRI检查。比较血糖正常组及高、低血糖组早产儿脑损伤的发生率。结果血糖正常组脑损伤发生率为5.66%(3/53例),低血糖组脑损伤发生率为20.29%(14/69例),高血糖组脑损伤发生率为37.50%(6/16例)。血糖异常持续时间越长,脑损伤发生率越高,而持续高血糖引起早产儿脑损伤的比率大于低血糖组,但无统计学差异。结论早产儿血糖异常波动是导致早产儿脑损伤的重要原因之一,血糖异常持续时间越长,早产儿脑损伤的发生率越高。     

妊娠期糖尿病母亲的新生儿出生48小时内血糖的动态变化及低血糖的影响因素

摘要目的：探讨糖尿病母亲婴儿（IDMS）出生后血糖的变化情况,分析IDMS发生低血糖的可能影响因素。方法：回顾性横断面调查,纳入2014年1月1日至12月31日在福建省妇幼保健院（我院)定期产检和分娩、单胎活产的全部妊娠期糖尿病（GDM）产妇,收集产妇和新生儿的一般临床资料、母亲孕产期血糖值和IDMS出生后48 h内各时点的血糖值。血糖值＜2.2 、~2.6 mmol·L-1 为低血糖和临界低血糖。多因素Logistic回归分析IDMS低血糖、临界低血糖的影响因素。结果：共1 083份病志进入本文分析。①GDM产妇年龄(30.2±4.2)岁,(39.1±1.4)孕周,初产妇66.8%,阴道分娩82.4%,孕前BMI＜18.5者4.5%、≥25者9.8%。1 083例IDMS中,早产儿3.8%,男52.5%,Apgar评分均≥8分,出生体重(3 303.7±428.2)g。②IDMS出生0.5 h时平均血糖明显下降,2~48 h呈上升趋势。母亲孕前BMI 18.5~24.9、阴道分娩、足月儿、总产程时间≥7 h、傍晚至夜间分娩、正常体重儿的IDMS出生时和生后某些时点的平均末梢血糖相对较高。③1 083例IDMS中,低血糖7例(0.65%),6例发生在出生时,1例发生在生后48 h;临界低血糖29例(2.68%),26例发生在出生时,生后12、24和48 h各1例。④多因素非条件Logistic回归显示,孕末期静脉血糖水平高是新生儿低血糖、临界低血糖的保护因素。结论：IDMS生后48 h内发生低血糖的时间以出生时最多,但生后48 h都有发生低血糖的可能,应密切监测。GDM孕妇孕末期静脉血糖水平高可能是新生儿低血糖和临界低血糖的保护因素。     

Clinical features and EEG monitoring ofneonatal hypoglycemic brain injury

目的 探讨新生儿低血糖脑损伤(HBD)时的脑电图(EEG)改变与临床预后关系,为HBD的诊断及预防提供依据.方法 监测住院新生儿血糖并描记入院后24-72 h的EEG,低血糖新生儿于入院后2周再次EEG检查.分析比较低血糖新生儿与正常血糖新生儿,以及无症状性与症状性低血糖患儿EEG的异常率以及预后.结果 人组100例新生儿,其中低血糖组52例,正常血糖组48例;低血糖组新生儿中症状性低血糖25例,无症状性低血糖27例.EEG异常率低血糖组新生儿73.1%(38/52),正常血糖组12.5%(6/48),两者差异有统计学意义(χ2=37.17,P<0.05).低血糖组新生儿中,症状性低血糖组EEG异常率96%(24/25).无症状性低血糖组51.9%(14/27),两者差异有统计学意义(χ2=10.7,P<0.05).新生儿血糖越低、持续时间越长,则EEG异常越严重.EEG中重度异常新生儿,大多遗留认知障碍、癫癎、脑瘫等后遗症.结论 新生儿HBD与低血糖的严重程度及持续时间密切相关.EEG能客观、直接地反映脑细胞的功能状态及损害程度,有助于早期评估脑损伤的程度及预后.     

新生儿低血糖脑损伤临床特征与脑电图监测

目的探讨新生儿低血糖脑损伤(HBD)时的脑电图(EEG)改变与临床预后关系,为HBD的诊断及预防提供依据。方法监测住院新生儿血糖并描记入院后24～72 h的EEG,低血糖新生儿于入院后2周再次EEG检查。分析比较低血糖新生儿与正常血糖新生儿,以及无症状性与症状性低血糖患儿EEG的异常率以及预后。结果入组100例新生儿,其中低血糖组52例,正常血糖组48例;低血糖组新生儿中症状性低血糖25例,无症状性低血糖27例。EEG异常率低血糖组新生儿73.1%(38/52),正常血糖组12.5%(6/48),两者差异有统计学意义(χ2=37.17,P<0.05)。低血糖组新生儿中,症状性低血糖组EEG异常率96%(24/25),无症状性低血糖组51.9%(14/27),两者差异有统计学意义(χ2=10.7,P<0.05)。新生儿血糖越低、持续时间越长,则EEG异常越严重。EEG中重度异常新生儿,大多遗留认知障碍、癫疒间、脑瘫等后遗症。结论新生儿HBD与低血糖的严重程度及持续时间密切相关。EEG能客观、直接地反映脑细胞的功能状态及损害程度,有助于早期评估脑损伤的程度及预后。     

新生儿低血糖(附87例临床分析)

新生儿低血糖是早产儿、小于胎龄儿、新生儿窒息等疾病的常见并发症.本症多无明显临床症状,易与新生儿期其他疾病症状相混淆,如不早期诊断和及时处理,反复发作常导致永久性脑损伤。近几年来,我们对围产期易并发低血糖的疾病进行血糖监测.现报告如下.     

早产儿低血糖与血清C肽检测的相关性分析

目的 探讨早产儿低血糖与血清C肽间的关系。方法 选择50例血糖正常的早产儿作为对照组，50例低血糖早产儿作为观察组，检测两组患儿的空腹血糖，动态监测低血糖患儿的血糖，并检测两组早产儿的血清C肽，对检测值进行比较及分析。结果 （1）早产儿低血糖无明显临床表现，可反复发作，其血糖纠正的时间与初始低血糖程度呈负相关（r=-0．674，P〈0．01）。（2）两组早产儿血清C肽检测结果比较差异无显著性（P〉0．05）。结论 早产儿低血糖临床症状不典型，应注意检测。早产儿胰岛B细胞分泌功能基本成熟。     

低出生体重儿生后早期动态血糖监测研究

新生儿低血糖是新生儿惊厥、呼吸暂停等严重症状的原因之一，低血糖持续时间较长可造成广泛脑损伤,导致死亡或智力发育障碍等后遗症，由于其多无症状,有症状也缺乏特异性，因此，确诊有赖于实验室血糖测定，为探讨新生儿血糖和体重关系，我们对91例低出生体重儿和216例正常体重儿末梢微量血血糖进行了监测，结果报告如下。     

糖尿病母亲婴儿并发症的临床观察

目的 探讨糖尿病母亲婴儿(infants of diabetic mothers,IDMS)并发症的发生情况.方法回顾性分析52例IDMS和50例非糖尿病母亲娩出的正常新生儿(对照组)的并发症发生情况.结果52例IDMS患儿发生低血糖23例(44.2％,23/52),高胆红素血症16例(31.4％,16/52),红细胞增多症11例(21.2％,11/52),巨大儿11例(21.2％,11/52),新生儿呼吸窘迫综合征4例(7.7％,4/52),先天畸形1例(1.9％,1/52).对照组50例患儿中有1例发生低血糖(2％,1/50),高胆红素血症7例(14.0％,7/50),红细胞增多症1例(2％,1/50).两组患儿在低血糖、高胆红素血症、红细胞增多症3种并发症方面比较,差异有统计学意义(P值分别为0.000、0.043和0.009).结论IDMS出现并发症的发生率高于正常新生儿,应对其进行严密监护.     

Research progress in neonatal hypoglycemic brain injury

<正>新生儿低血糖是早产儿、小于胎龄儿及糖尿病母亲婴儿等的常见并发症,目前对新生儿低血糖的诊断与临床干预有了较深入的认识,但是新生儿低血糖出现脑损伤的血糖阈值和时间域值并不清楚,持续或反复的低血糖可导致新生儿永久性脑损伤,遗留认知障碍、视觉障碍、枕叶癫癎、脑瘫等后遗症。部分临床医师对新生儿低血糖性脑损伤也缺乏充分的认识,诊断标准有待建立[1]。现就新生儿低血糖     

Effects of maternal labetalol on the newborn infant.

Forty eight neonates, born to mothers suffering from pregnancy induced hypertension and receiving labetalol for control of blood pressure, were studied for the possible adverse effects of the drug. These were compared with eighty one neonates matched for gestation and weight and born to mothers with pregnancy induced hypertension treated with drugs other than labetalol. Incidence of birth asphyxia and intrauterine growth retardation (IUGR) in the study population was 10.4 and 22.9%, respectively and in the control group 5 and 19.7%, the difference between two groups was not statistically significant (p > 0.05). However, the incidence of hypoglycemia was significantly higher (p < 0.01) in the study group (47.9%) as compared to the control group (17.2%). Two-thirds of the hypoglycemic babies in the study population were asymptomatic and they were managed with sugar-fortified milk feeds. In the study population, the symptomatic hypoglycemic babies had hypoglycemia for prolonged duration of 43.3 +/- 23.3 hours as compared to 11.5 +/- 6.3 hours in symptomatic hypoglycemic babies of the control group (p < 0.01). The mothers of the symptomatic babies in the study group received higher doses of labetalol in the range of 287.6 +/- 142.3 mg/day while rest of the mothers in the same group whose babies had either asymptomatic hypoglycemia or normal blood glucose levels, received 239.5 +/- 118.5 mg/day, though the difference was not statistically significant. It is concluded that maternal labetalol therapy is associated with increased risk of neonatal hypoglycemia.     

Hypoglycemic brain injury

Hypoglycemia frequently occurs in newborn infants who previously have suffered asphyxia, who are offspring of diabetic mothers, or who are low birthweight for gestational age (IUGR). Many infants who are hypoglycemic do not exhibit clinical manifestations, while others are symptomatic and at risk for the occurrence of permanent brain damage. This review emphasizes the clinical, neuropathologic, and neuro-imaging features of hypoglycemia in newborn infants, especially those who are symptomatic. Neurologic morbidity occurs particularly in those infants who have suffered severe, protracted, or recurrent symptomatic hypoglycemia. Experimental observations emphasize the resistance of the immature brain to the damaging effect of hypoglycemia; such resistance occurs as a consequence of compensatory increases in cerebral blood flow, lower energy requirements, higher endogenous carbohydrate stores, and an ability to incorporate and consume alternative organic substrates to spare glucose for energy production. Hypoglycemia combined with hypoxia-ischemia (asphyxia) is more deleterious to the immature brain than either condition alone.     

Neonatal hypoglycemia--clinical profile and glucose requirements.

A total of 2248 infants born at All India Institute of Medical Sciences Hospital, New Delhi were selectively screened for hypoglycemia over a period of 15 months. Hypoglycemia (blood glucose less than 30 mg/dl) was diagnosed in 107 cases (4.8%). Preterm babies had three times increased risk (12.8%) as compared to term babies (3.6%). Small-for-dates (SFDs) and large-for-dates (LFDs) infants were at increased risk of manifesting hypoglycemia (7 and 10 times, respectively) as compared to the appropriate-for-dates (AFDs) babies (2.7%). Approximately two-thirds of the hypoglycemic babies (67.3%) had one or more risk factors including birth asphyxia (24.2%), diabetic mothers (23.8%), respiratory distress (13.9%) and septicemia (11.6%). A total of 59.8% cases were asmyptomatic while the rest had one or more symptoms. The most common symptom observed was lethargy (81.4%), followed by jitteriness (67.4%), respiratory abnormalities (41.9%), hypotonia (39.5%) and seizures (30.2%). The amount of glucose (mg/kg/min) needed to maintain a stable blood sugar in various categories of hypoglycemic babies was observed to be in the following decreasing order of amount; symptomatic babies with seizures (Gp IV), IGDM's/IDM's and symptomatic babies with other features (Gp III), SFDs and LFDs (Gp II) and AFDs (Gp I). Such a categorization of hypoglycemic babies will help to treat them more precisely.     

Glucose disappearance in infants of diabetic mothers I. Relationship to maternal glucose tolerance and insulin production

Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.     

Glucose disappearance in infants of diabetic mothers. III. Relationship of spontaneous glucose disappearance to glucose tolerance,neonatal hypoglycemia and lowest blood glucose

Spontaneous glucose disappearance in the first 90 min of life and glucose disappearance following an intravenous injection of 1 g/kg dextrose were measured in 23 infants of insulin-dependent diabetic mothers. Spontaneous disappearance was log-linear in 12/23 infants, providing for calculation of an endogenous K_t which correlated significantly (P < 0.01) with the exogenous Kt determined after the dextrose injection, r = 0.74.Hypoglycemia <20 mg/dl occurred in 4/23 infants, and was identified during the spontaneous glucose disappearance (3 infants) and/or predicted by an endogenous K_t > 3.0%/min (2 infants). There was also a significant inverse correlation (P < 0.01) of the lowest blood glucose obtained within the first 24 h of life with the endogenous K_t, r = 0.61. There was no correlation of the endogenous or exogenous Kt, lowest blood glucose or hypoglycemia with White's classification of the maternal diabetes, diabetic control during pregnancy, the maternal blood glucose at delivery or the cord blood glucose.These data indicate that determination of spontaneous glucose disappearance within the first 90 min of life is useful in identifying infants of diabetic mothers with hypoglycemia or those who will subsequently develop hypoglycemia.     

Prediction of neonatal hypoglycemia in infants of diabetic mothers by glucose disappearance in the first hour of life

Whole blood glucose determinations were obtained in the first hour of life in 44 infants of diabetic mothers in order to predict the occurrence of subsequent hypoglycemia by means of the calculated glucose disappearance rate. Hypoglycemia (whole blood glucose < 20 mg/dl) occurred in 10 infants with linear glucose disappearance of whom 9 had a glucose disappearance rate ? 3.0% per min (90% sensitivity). Nine of 11 infants with glucose disappearance rates ? 3.0% per min had hypoglycemia (82% specificity). This relatively simple procedure offers an accurate method for prediction of neonatal hypoglycemia due to reactive hyperinsulinemia in infants of diabetic mothers.     

Asymmetric septal hypertrophy in infants of diabetic mothers. Fetal echocardiography and the impact of maternal diabetic control.

Maternal hyperglycemia may result in fetal hyperinsulinemia and asymmetric septal hypertrophy, macrosomia, and hypoglycemia in infants of diabetic mothers. We monitored glycosylated hemoglobin levels in 61 pregnant diabetic women each trimester as an index of maternal glycemic control and did serial fetal echocardiograms starting at 18 weeks of gestation. At delivery, cord blood C-peptide levels were obtained as an index of fetal hyperinsulinemia. Infants were assessed for hypoglycemia, macrosomia and septal thickening by echocardiography. Nineteen of the 61 infants (31%) had septal hypertrophy, were heavier, and had higher cord blood C-peptide levels and lower serum glucose levels than unaffected infants. Maternal glycosylated hemoglobin levels were higher during the third trimester in mothers of affected infants. Our data support a possible relationship between third-trimester maternal hyperglycemia and neonatal asymmetric septal hypertrophy, macrosomia, and hypoglycemia.     

Hypoglycemia in newborn infants: Features associated with adverse outcomes

The purpose of this review article is to document from the literature values of blood/plasma glucose concentration and associated clinical signs and conditions in newborn infants (both term and preterm) that indicate a reasonable clinical probability that hypoglycemia is a proximate cause of acute and/or sustained neurological injury and to review the physiological and pathophysiological responses to hypoglycemia that may influence the ultimate outcome of newborns with low blood glucose. Our overall conclusion is that there is inadequate information in the literature to define any one value of glucose below which irreparable hypoglycemic injury to the central nervous system occurs, at any one time or for any defined period of time, in a population of infants or in any given infant. Clinical signs of prolonged and severe neurological disturbance (coma, seizures), extremely and persistently low plasma/blood glucose concentrations (0 to <1.0 mmol/l [0 to <18-20 mg/dl] for more than 1-2 h), and the absence of other obvious central nervous system (CNS) pathology (hypoxia-ischemia, intracranial hemorrhage, infection, etc.) are important for the diagnosis of injury due to glucose deficiency. Specific conditions, such as persistent hyperinsulinemia with severe hypoglycemic episodes that include seizures, also contribute to the diagnosis of hypoglycemic injury. Such lack of definitive measures of injury specific to glucose deficiency indicates that clinicians should be on the alert for infants at risk of hypoglycemia and for clinical signs and conditions that might herald severe hypoglycemia; they should have a low threshold for investigating and diagnosing 'hypoglycemia' with frequent measurements of plasma/blood glucose concentration; and they should treat low glucose concentrations promptly and maintain them in a safe range. Because there is no conclusive evidence or consensus in the literature that defines an absolute value or duration of 'hypoglycemia' that must occur, with our without related clinical complications, to produce neurological injury, clinicians should consider the information currently available, determine a 'target' plasma or blood glucose concentration that is acceptable, and treat infants with glucose concentrations below this value accordingly. Our intent in this review article is to highlight the studies relevant to this issue and help clinicians formulate a safe and, hopefully, effective strategy for the diagnosis and treatment of hypoglycemia.