糖尿病母亲婴儿低血糖发生情况及其与脑损伤的关系

目的探讨糖尿病母亲婴儿（IDMS）低血糖的发生情况及其与脑损伤的关系。方法分析86例IDMS低血糖的发生情况、母亲孕期血糖控制与低血糖持续时间的关系。分析其脑损伤发生及严重程度与低血糖持续时间、并其他疾病和症状性低血糖的关系。结果短暂性低血糖75例（87.2%）,反复发作性低血糖11例（12.8%）。母亲孕期血糖反复发作性低血糖发生率控制不满意组为19.4%,满意组为8%。反复发作性低血糖组脑损伤总发生率及重度脑损伤发生率高于短暂性低血糖组,并其他疾病组48.5%和无临床症状组57.4%,均有显著性差异（Pa〈0.05）。结论低血糖的持续时间与母亲妊娠期血糖控制情况及脑损伤发生、严重程度有关;低血糖并其他疾病会加重脑损伤,症状性低血糖时常存在严重脑损伤。     

Transient hyperinsulinism in asphyxiated newborn infants

Hypoglycemia in birth asphyxiated infants is attributed to glycogen depletion. We observed three term AGA (Appropriate for Gestational Age) infants with birth asphyxia, who developed hyperinsulinemic hypoglycemia postnatally. All had inappropriately high serum insulin concentrations for their blood glucose levels, and needed glucose infusion rates of greater than 8 mg/kg/min for several days to maintain normoglycemia. All infants recovered spontaneously.     

血清S100B蛋白在新生儿窒息后脑损伤中的临床意义

目的：S100B蛋白是一种脑特异性蛋白,可反映脑损伤的程度。该研究旨在探讨窒息新生儿脐血及生后血清S100B蛋白的变化及对新生儿窒息诊断和窒息后脑损伤判断的价值。方法：对窒息新生儿的脐血及生后1,3,7d血清S100B蛋白变化进行分析。结果：①窒息新生儿脐血S100B蛋白水平高于正常对照组,差异有显著性(P<0.05),轻度窒息与重度窒息患儿脐血S100B蛋白含量差异无显著性;②出生后1～7d内轻度窒息患儿血清S100B蛋白无明显变化,重度窒息脑损伤患儿血清S100B蛋白呈逐渐增高趋势,生后第7天时重度窒息脑损伤患儿血清S100B蛋白明显高于轻度窒息患儿(P<0.01);③死亡的窒息患儿生后第7天的血清S100B蛋白含量高于存活儿,但差异无显著性(P>0.05);④发生颅内出血和/或脑水肿的患儿生后第3天血清S100B蛋白含量增高,差异有显著性(P<0.05)。结论：血清S100B蛋白检测有助于新生儿窒息的诊断及窒息后脑损伤的判断。     

Prolonged hyperinsulinemic hypoglycemia in a small for date preterm

Hyperinsulinism is an important cause of hypoglycemia in early infancy. Many forms of hyperinsulinemic hypoglycemia are described: transient, prolonged, persistent. Transient forms are well recognized in infants of diabetic mother; prolonged forms are responsible for the hypoglycemia in small-for-date (SGA) infants and asphyxiated newborns. Persistent hyperinsulinemic hypoglycemia occurs in a group of congenital disorders associated with an abnormality of beta-cell regulation throughout the pancreas. Accurate diagnosis and treatment are essential in all various forms of hyperinsulinism also because newborns are at high risk of permanent brain damage. We report a case of prolonged hyperinsulinemic hypoglycemia in a SGA preterm, immediately treated with a high dose of glucose and glucocorticoid and then with diazoxide. Hypoglycemia was continued until 2 months of age when it resolved spontaneously and completely.     

ON THE DIAGNOSIS OF SYMPTOMATIC NEONATAL HYPOGLYCEMIA

Eighteen newborn infants, 11 males and 7 females, with hypoglycemia, i.e. with blood glucose concentration of less than 20 mg per 100 ml were studied. Twelve infants were diagnosed as cases of symptomatic and 6 as cases of asymptomatic hypoglycemia. All infants with asymptomatic hypoglycemia were small for gestational age, whereas the symptomatic group was heterogenous from a clinical point of view. The disappearance rate of intravenously administered glucose (k_G-value) was studied before any treatment was started. The k_G-values were high in all infants with symptomatic hypoglycemia, in 10 exceeding +2 s.D. for normal infants of the same age. The symptomatic infants were treated with hydrocortisone or human growth hormone in addition to continuous glucose infusion. After the institution of therapy there was a rapid normalization of the k_G-values. The 6 infants with asymptomatic hypoglycemia had normal k_G;-values. They were only given a high caloric supply by means of breast milk. In two infants with symptomatic hypoglycemia repeated simultaneous determinations of k_G-values and the plasma concentration of free fatty acids revealed no relationship. At follow-up examinations at ages from 5 months to 2 years, 2 out of the 12 infants in the symptomatic group were found to have severe cerebral damage. All infants with asymptomatic hypoglycemia were completely normal. The findings seem to have some clinical applications. Determination of the disappearance rate of intravenously administered glucose, primarily given as a diagnostic test, may differentiate between symptomatic and asymptomatic hypoglycemia. If in a doubtful case the k_G-value is normal, the likely diagnosis is asymptomatic hypoglycemia. In cases of symptomatic neonatal hypoglycemia repeated determinations of the k_G-value may provide a sensitive guide as to the effect of treatment.     

Transient tricuspid insufficiency of the newborn: a form of myocardial dysfunction in stressed newborns.

Fourteen term newborn infants have been recognized as having transient tricuspid insufficiency associated with significant perinatal stress. Five of these infants underwent cardiac catheterization for presumed congenital heart disease, but had only massive tricuspid valve insufficiency. The other nine infants were diagnosed on the basis of a murmur characteristic of tricuspid valve insufficiency and on other clinical grounds. All had a history of significant perinatal stress in the form of asphyxia with or without hypoglycemia. Frequently, congestive heart failure, persistent cyanosis, and ECG evidence of myocardial ischemia were present. Twelve of the 14 survived, and in each of them all cardiac signs and symptoms, including the murmur, spontaneously resolved. The two patients who died had histopathologic evidence of necrosis in the anterior papillary muscle of the tricuspid valve. The constant features of perinatal stress, ST-T wave abnormalities on the ECG, and spontaneous resolution of the transient tricuspid insufficiency strongly suggest that this syndrome is secondary to a reversible form of myocardial dysfunction, perhaps by affecting papillary muscle specifically. We believe that hypoxia with or without hypoglycemia precipitates the events leading to this clinical syndrome which is distinguishable from other cardiac abnormalities in the newborn by the history, distinctive murmur, and the ECG abnormalities.     

新生儿糖代谢紊乱的临床研究

目的分析新生儿糖代谢紊乱的相关因素,探讨其预防和治疗措施。方法住院新生儿1783例进行血糖监测。所有息儿监测至2次空腹血糖正常为止。计数资料采用X2检验。结果发生糖代谢紊乱295例,其中低血糖症176例,高血糖症52例,二者兼有67例。血糖异常与胎龄呈显著负相关(P=0.001);与出生体质量呈显著负相关(P<0.01);小于胎龄儿(SGA)易发生糖代谢紊乱;轻度窒息组血糖紊乱以低血糖症为主,重度窒息组血糖紊乱以高血糖症居多(P<0.01);血糖恢复时间与窒息程度呈显著正相关(P<0.01);血糖异常与感染程度星显著正相关(P=0.019);糖尿病母亲婴儿易患低血糖症。结论对高危儿应尽早进行血糖监测,对血糖异常者及时处理,以减少或避免后遗症发生。     

The Scottish perinatal neuropathology study: clinicopathological correlation in early neonatal deaths

BACKGROUND: A proportion of neonatal deaths from asphyxia have been shown to be associated with pre-existing brain injury. OBJECTIVES: (a) To compare the epidemiology of infants displaying signs of birth asphyxia with those not showing signs; (b) to examine the neuropathology and determine if possible the timing of brain insult comparing asphyxiated with non-asphyxiated infants; (c) to compare the clinical features of those born with birth asphyxia with and without pre-labour damage. METHODS: Over a two year period, all 22 Scottish delivery units collected clinical details on early neonatal deaths. Requests for post mortem included separate requests for detailed neuropathological examination of the brain. Infants were classified into two groups: birth asphyxia and non-birth asphyxia. Clinicopathological correlation was used to attempt to define the time of brain insult. RESULTS: Detailed clinical data were available on 137 of 174 early neonatal deaths that met the inclusion criteria. Seventy of 88 parents who had agreed to post mortem examination consented to a detailed examination of additional samples from the brain; in 53 of these cases the infant was born in an asphyxiated condition. All asphyxiated and encephalopathic infants, 38% of mature and 52% of preterm infants with features of birth asphyxia but without encephalopathy, and only one of 12 infants without any signs of birth asphyxia showed damage consistent with onset before the start of labour. CONCLUSIONS: In a large proportion of neonatal deaths, brain injury predates the onset of labour. This is more common in infants born in an asphyxiated condition.     

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??Abstract?? Objective??To study the diagnosis and treatment of neonatal Congenital Hyperinsulinism Hypoglycemia??CHI??. Methods??The clinical data of 15 newborn babies with CHI??who were diagnosed in Beijing Children’s Hospital between 2000 and 2010??were retrospectively reviewed. Results??Sex ratio of boys to girls was 10??4. Time variation in disease onset?? from less than 1 hour after labor to 25 days. ten of 15 patients were large for gestational age?? 8 of them were macrosonias. Convulsion??cyanosis??lethargy??refusing milk sucking??irritability and sweating were common symptoms. The laboratory findings displayed persistent hypoglycemia and hyperinsulinism in all of the 15 newborn babies. There were no urine and blood ketones elevating in all of the 15 newborn babies. Nine infants were treated with oral diazoxide??but only 2 of them showed effectiveness to the therapy. One patient was given subtotal pancreatectomy and the blood glucose level was restored to normal after operation. Two newborn babies died within 2 weeks. Of the other 13 newborn babies??only 3 who were effectively treated had normal intelligence. Nine of them presented mental retardation in a 5-year follow-up. Conclusion??The measurement of blood glucose??blood insulin and urinary ketones is helpful in the diagnosis of persistent hyperinsulinemic hypoglycemia of infancy. Most patients have no response to diazoxide therapy. Whenever drug treatment is comfirmed unresponsive??operation should be considered.     

Cerebral metabolism during hypoglycemia dn asphyxia in newborn dogs

The cerebral metabolic responses to perinatal hypoglycemia (blood glucose less than or equal to 1 mmol/l) combined with asphyxia were studied in paralyzed, lightly anesthetized newborn dogs. No major differences in heart rate, blood pressure or arterial acid-base balance between control and hypoglycemic animals occurred either prior to or during asphyxia. The electroencephalogram, unaltered by hypoglycermia alone, became isoelectric at the same intervals in both groups following respiratory arrest. Intravenous carbon black infusion at 5 min of asphyxia demonstrated no relationship between blood glucose level and cerebral perfusion (p > 0.05), whereas a positive correlation did exist between systemic blood pressure and cerebral perfusion (p < 0.01). During asphyxia, anaerobic glycolysis in brain was less enhanced in hypoglycemic dogs, resulting in a more rapid exhaustion of high-energy phosphate reserves (phosphocreatine, ATP and ADP). Thus, the cerebral metabolic responses to asphyxia superimposed upon hypoglycemia were the direct consequence of insufficient cerebral glucose stores coupled with deficient circulating glucose to brain. These metabolic disturbances were no more the result of cerebral ischemia than that which occurs during asphyxia alone. The findings also suggest that systemic physiological monitoring may be an inadequate means of appraising cerebral homeostasis during combined hypoglycemia ad hypoxia.     

Perinatal asphyxia: a clinical review,including research with brain hypothermia

Perinatal asphyxia may occur in utero, during labor and delivery, or in the postnatal period. There are numerous causes, and the clinical manifestations vary. Infants who experience mild asphyxia may show no neurologic injury. Severe asphyxia may be fatal in utero, or immediately after birth, with survivors showing extensive neurologic sequelae, with or without cognitive deficits. Mild brain hypothermia appears promising in the prevention of further neurologic damage in encephalopathic infants following asphyxia. Recent research on newborn animal models has focused on the timing, duration, and depth of hypothermia. Promising new research is now under way in nurseries in the U.S. in an attempt to establish clinical protocols for use of hypothermia in human neonates.     

Increased brain levels of F2-isoprostane are an early marker of behavioral sequels in a rat model of global perinatal asphyxia

Perinatal asphyxia is a major cause of immediate and postponed brain damage in the newborn. It may be responsible for several delayed neurologic disorders and, in this respect, early markers of brain injury would be relevant for therapeutic intervention as well as for identification of infants at high risk for developmental disabilities. Biochemical measurements (brain F2-isoprostane levels) and behavioral tests (ultrasonic vocalization pattern on postnatal days (pnd) 5, 8, and 11, spontaneous motor behaviors on pnd 7 and 12, and homing response on pnd 10) were performed in a rat model of global perinatal asphyxia in the immature neonate. Caesarean section was performed in rats and the pups, still in uterus horns, were placed into a water bath at 37 degrees C for either 10 or 20 min. Caesarean delivered pups were used as controls. Pups experiencing severe (20 min), in contrast to those undergoing the 10 min, asphyctic insult presented with detectable abnormalities including early (two hours after the insult) increase in brain F2-isoprostane (a direct marker of oxidative injury) without detectable changes in PGE2, COX-2 and iNOS levels, and delayed physical (reduced weight gain on pnd 5 and thereafter) and behavioral disturbances (alterations in ultrasound emission on pnd 11 and spontaneous motricity levels mainly). These findings suggest that increased brain F2-isoprostane levels shortly after the asphyctic insult are predictive of delayed behavioral disturbances in the newborn rat. The present 20-min asphyxia model might serve for the assessment of preventive and curative strategies to treat neurologic/behavioral disturbances associated with perinatal asphyxia.     

86例新生儿低血糖临床病因及治疗分析

目的 分析致新生儿低血糖的因素、临床表现及治疗,为临床诊治提供可借鉴的依据.方法 对可能发生低血糖的278例新生儿进行血糖测定.结果 共测出86例为低血糖,临床表现为多样性,原发基础疾病:窒息35例(40.7%),早产儿及小于胎龄儿27例(30.7%),喂养障碍12例(13.9%),感染6例(7.0%),母亲患糖尿病者4例(4.7%).出血病2例(2.3%).结论 对存在新生儿低血糖发病因素者要及时测定血糖,以利于早发现、早治疗,避免因低血糖而致中枢神经的损伤.     

NEONATAL HYPOGLYCEMIA II. A Clinical Study of 44 Idiopathic Cases with Special Reference to Corticosteroid Treatment

Forty-four newborn infants with significant hypoglycemia, i. e. with two or more true blood glucose values of 20 mg/100 ml or less, have been studied. Two thirds of the patients were males, and a similar proportion had low birth weight for gestation, mostly associated with maternal toxemia. Hypoglycemia was diagnosed during the first day of life in 34 cases. Only three infants were asymptomatic, whereas the others exhibited various nonspecific symptoms, which generally were more severe in patients aged two or three days. A therapeutic test with glucose was positive in only 20 infants, and mostly negative before 24 hours of age. The hypoglycemia was transient in all cases. Mental retardation with spasticity and infantile spasms has developed in four infants by the age of six months, and one of them died at the age of eight months. The others appear normal after 4–26 months of observation. A significant effect of hydrocortisone in shortening the duration of hypoglycemia was demonstrated. On the basis of experience with the patients reported, it is suggested that all infants with significant hypoglycemia should be efficiently treated, regardless of symptomatology.     

A comparison of the mid-arm circumference/head circumference ratio and ponderal index for the evaluation of newborn infants after abnormal intrauterine growth

We studied the accuracy of the ponderal index and the mid-arm circumference/head circumference ratio for detecting newborn infants who were likely to be symptomatic because of aberrant intrauterine growth. Sixty infants were evaluated because of suspected intrauterine growth retardation; both the mean ponderal index and mid-arm circumference/head circumference ratio were significantly lower in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants (p less than 0.05). However, the mid-arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (80% vs. 47%; p = 0.007). An additional 60 infants were evaluated because of suspected abnormal intrauterine growth acceleration. The mean mid-arm circumference/head circumference ratio, but not the ponderal index, was significantly higher in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants (p less than 0.005). Again, the mid-arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (79% vs. 33%; p less than 0.001). The mid-arm circumference/head circumference ratio is more accurate than the ponderal index for the evaluation of potentially symptomatic newborn infants who suffered abnormal fetal growth. The ponderal index is not useful for the detection of symptomatic large-for-dates infants.     

A Comparison of the Mid-Arm Circumference/Head Circumference Ratio and Ponderal Index for the Evaluation of Newborn Infants after Abnormal Intrauterine Growth

ABSTRACT. We studied the accuracy of the ponderal index and the mid-arm circumference/head circumference ratio for detecting newborn infants who were likely to be symptomatic because of aberrant intrauterine growth. Sixty infants were evaluated because of suspected intrauterine growth retardation; both the mean ponderal index and mid-arm circumference/head circumference ratio were significantly lower in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants ( p <0.05). However, the mid-arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (80% vs. 47%; p =0.007). An additional 60 infants were evaluated because of suspected abnormal intrauterine growth acceleration. The mean mid-arm circumference/head circumference ratio, but not the ponderal index, was significantly higher in the group of 30 symptomatic infants than in the group of 30 asymptomatic infants ( p <0.005). Again, the mid-arm circumference/head circumference ratio identified a significantly higher percentage of the symptomatic infants than the ponderal index (79% vs. 33%; p <0.001). The mid-arm circumference/head circumference ratio is more accurate than the ponderal index for the evaluation of potentially symptomatic newborn infants who suffered abnormal fetal growth. The ponderal index is not useful for the detection of symptomatic large-for-dates infants.     

Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy

OBJECTIVES: To determine plasma and cerebrospinal fluid (CSF) levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: A controlled, prospective study of 20 control neonates, 19 term newborn infants presenting with sepsis and no meningitis, and 19 asphyxiated term newborn infants. Blood and CSF samples were collected within 48 hours of birth for IL-6 and TNF-alpha determinations. RESULTS: Median plasma IL-6 was similar in sepsis and asphyxia but significantly higher than in control neonates. Median plasma TNF-alpha was similar in asphyxia and control neonates but significantly lower than in sepsis. In asphyxiated newborn infants, median CSF IL-6 and TNF-alpha were significantly higher than in sepsis and control neonates. Median CSF IL-6 was significantly higher in sepsis than in control neonates. Median CSF TNF-alpha was similar in newborn infants with sepsis and control neonates. IL-6 and TNF-alpha CSF/plasma ratios were similar in newborn infants with sepsis and control neonates but lower than in asphyxiated newborn infants. CONCLUSIONS: Term newborn infants with HIE have elevated CSF IL-6 and TNF-alpha levels. Plasma IL-6 is increased in asphyxia and sepsis. Plasma TNF-alpha is increased only in sepsis. High IL-6 and TNF-alpha CSF/plasma ratios in asphyxia suggest that these cytokines are produced in the brain of term newborn infants with HIE.     

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.     

新生儿低血糖脑损伤的临床研究

目的探讨低血糖脑损伤的临床表现与早期影像学特征,为诊断与预后判定提供依据。方法6例人院时血糖为0.48～1.70mmol/L。胎龄35周^＋5至40周,出生体重1545～3900g。均无窒息史、败血症、颅内感染、遗传代谢及内分泌性疾病。在入院24～48h完成T1WI、T2WI和DWI磁共振扫描。结果6例均有明显的临床表现,以惊厥、萎靡最为常见,其次为呼吸暂停,4例血糖正常时仍有惊厥发生。5例低血糖发生在生后6～53h,1例在生后12d。低血糖持续时间[（47.7±38.8）（4～96）]h,最低值[（1.05±0.44）（0.48～1.70）]mmol／L。首次MRI检查1例在生后15d,余在生后2～5d,受累部位为枕叶（6例）和顶叶（3例）皮层及皮层下白质：DWI上表现为高信号6例,TlwI为低信号4例,T2WI高信号1例。3例在生后第2周接受第2次检查,1例DWI转为低信号,余信号正常;3例此时TlwI和T2W1分别表现为低信号和高信号,局部水肿明显减轻。1例3个月随访发育正常,未见顶枕部萎缩,但内囊后枝和视放射髓鞘化不良。结论枕顶叶是新生儿低血糖脑损伤的主要受累部位,DWI可以早期反映脑损伤的改变。     

Endocrine-induced forms of hypoglycemia

Hypoglycemia due to endocrine disorders commonly manifests itself during the newborn period or in early infancy. Hyperinsulinism accounts for more than 50% of all cases of persistent hypoglycemia occurring during the first year of life. The underlying cause of hyperinsulinism is probably a functional dysregulation of the B cells of the pancreas. These patients suffer from severe, sometimes life-threatening hypoglycemia during their first hours and days of life. Hypoglycemia cannot be prevented by a high carbohydrate supply exceeding the endogenous glucose production rate of the liver. The diagnosis of hyperinsulinism is established by an increased insulin concentration (above 10-12 mU/l) during hypoglycemia (blood glucose less than 40 mg/dl). Macrosomia of these newborns without a history of maternal diabetes supports the diagnosis. Most of the patients require a 90%-95% pancreatectomy in order to prevent severe brain damage, as medical and dietary treatment are ineffective. Hypoglycemia due to panhypopituitarism, growth hormone deficiency and inherited glucocorticoid deficiency also develops during early infancy, but can be discriminated from hyperinsulinism by one important criterion: hypoglycemia can be avoided by continuous glucose infusion dosed at the endogenous glucose production rate. If additional symptoms are lacking the diagnosis has to be established by the plasma concentrations of the different hormones and provocation tests.