How much of neonatal encephalopathy is due to birth asphyxia?

In the literature on neonatal encephalopathy, the pervasive assumption is that once infants with major malformations or infections have been excluded, most of the remaining cases are due to birth asphyxia. Assessing the proportion of neonatal encephalopathy that is due to asphyxia during birth is difficult because of problems in defining asphyxia and neonatal encephalopathy and in recognizing the cause of neonatal neurologic illness. Available evidence indicates that neonatal neurologic signs are not strongly related to obstetric complications, signs of fetal distress, or biochemical markers usually considered to indicate perinatal asphyxia. Most studies that have sought positive evidence of independent markers of intrapartum asphyxia have found them to be absent in a large majority of neurologically symptomatic neonates. We conclude that the proportion of neonatal encephalopathy that is asphyxial in origin is not known but warrants examination, especially in view of the probable need in the near future to identify, on the basis of evidence available in the first hour or so of life, suitable candidates for clinical trials of powerful but risky treatments of birth asphyxia.     

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。     

Fetal and Neonatal Cortical Adrenal Function in Birth Asphyxia

ABSTRACT. Eighteen newborn infants, gestational age between 36 and 42 weeks with birth asphyxia were compared with 23 normal newborn infants to determine serum cortisol and dehydroepiandrosterone sulfate levels in cord blood and in venous blood samples collected 12–18 hours after birth. Both groups were similar in gestational age, birthweight, proportion of small for gestational age and large for gestational age infants, proportion of infants delivered by cesarean section with and without labor, and proportion of mothers with pre-eclampsia. There was no antenatal exposure to corticosteroid. The asphyxiated newborn infants had a significantly higher mean cord serum level of cortisol, and a significantly lower mean cord serum level of dehydroepiandrosterone sulfate than the control group. Mean serum cortisol and dehydroepiandrosterone sulfate levels collected 12–18 hours after birth were similar between both groups. It is suggested that elevated cord serum level of cortisol is related to birth asphyxia stress stimulating the adrenal definitive zone, and the low cord serum level of dehydroepiandrosterone sulfate is secondary to a transient hypoxemic-ischemic insult to the adrenal fetal zone.     

Fetal and neonatal cortical adrenal function in birth asphyxia

Eighteen newborn infants, gestational age between 36 and 42 weeks with birth asphyxia were compared with 23 normal newborn infants to determine serum cortisol and dehydroepiandrosterone sulfate levels in cord blood and in venous blood samples collected 12-18 hours after birth. Both groups were similar in gestational age, birthweight, proportion of small for gestational age and large for gestational age infants, proportion of infants delivered by cesarean section with and without labor, and proportion of mothers with pre-eclampsia. There was no antenatal exposure to corticosteroid. The asphyxiated newborn infants had a significantly higher mean cord serum level of cortisol, and a significantly lower mean cord serum level of dehydroepiandrosterone sulfate than the control group. Mean serum cortisol and dehydroepiandrosterone sulfate levels collected 12-18 hours after birth were similar between both groups. It is suggested that elevated cord serum level of cortisol is related to birth asphyxia stress stimulating the adrenal definitive zone, and the low cord serum level of dehydroepiandrosterone sulfate is secondary to a transient hypoxemic-ischemic insult to the adrenal fetal zone.     

Perinatal mortality in Jamaica 1986-1987

A large population-based study of all stillbirths and neonatal deaths occurring on the island of Jamaica during a 12 month period is described. During this time, 2069 perinatal deaths were identified in an estimated total of 54,400 infants born giving a perinatal death rate of 38.0 per 1000 births. The death rate was 5 times higher among twins than singletons. An attempt was made to obtain detailed postmortem examination of as many cases as possible. In the event, 51% of the infants who died perinatally had such postmortem examination. Postmortem rate was affected by sex, multiplicity of the infant, time of death, month of death and area of delivery. Deaths were classified using the Wigglesworth scheme. The distribution of categories was similar in the months when the postmortem rate was 70% to the rest of the time period when the post-mortem rate was only 40%. The Wigglesworth classification of deaths identified those associated with intrapartum asphyxia as the most important group, accounting for over 40% of deaths overall and 59% of deaths in infants of more than 2500 g birthweight. Antepartum fetal deaths were the second largest group, comprising 20% of deaths. Sixty percent of the infants in this group weighed less than 2500 g at birth. Major malformations were responsible for few perinatal deaths in Jamaica. This simple classification is important as it focuses attention on details of labour and delivery that may require change and is useful in planning future delivery of obstetric and neonatal care.     

Neonatal resuscitation after severe asphyxia - a critical evaluation of 177 Swedish cases.

AIM: To evaluate neonatal resuscitation of infants born with severe asphyxia. METHOD: All case records of the 472 claims for financial compensation due to suspected medical malpractice in conjunction with childbirth in Sweden between 1990 and 2005 were scrutinized. Inclusion criteria were: gestational age > or =33 completed weeks, planned vaginal onset of delivery, a reactive CTG at onset of labour, neonatal asphyxia (defined as metabolic acidosis [pH of < 7.05 and/or a base excess of < -12]), or an Apgar score <7 at 5 min. It was assessed that 177 infants suffered from cerebral palsy or early death due to severe asphyxia presumably caused by malpractice around labour. RESULTS: Median Apgar score at 5 min was 3, indicating that all infants needed immediate and extensive resuscitation. There was insufficient adherence to guidelines concerning neonatal resuscitation, including delayed initiation of excessive resuscitation in 19 infants, lack of satisfactory ventilation in 79 infants, and untimely interruption of resuscitation in 38 infants. CONCLUSIONS: Compliance with guidelines for resuscitation of severely asphyctic newborn may be improved, especially concerning ventilation and prompt paging for skilled personnel in cases of imminent asphyxia. Documentation of neonatal resuscitation must be improved to enable reliable evaluation.     

Perinatal Mortality in Jamaica 1986-1987

ABSTRACT. A large population-based study of all stillbirths and neonatal deaths occurring on the island of Jamaica during a 12 month period is described. During this time, 2069 perinatal deaths were identified in an estimated total of 54400 infants born giving a perinatal death rate of 38.0 per 1000 births. The death rate was 5 times higher among twins than singletons. An attempt was made to obtain detailed postmortem examination of as many cases as possible. In the event, 51 % of the infants who died perinatally had such postmortem examination. Postmortem rate was affected by sex, multiplicity of the infant, time of death, month of death and area of delivery. Deaths were classified using the Wigglesworth scheme. The distribution of categories was similar in the months when the postmortem rate was 70 % to the rest of the time period when the post-mortem rate was only 40 %. The Wigglesworth classification of deaths identified those associated with intrapartum asphyxia as the most important group, accounting for over 40 % of deaths overall and 59 % of deaths in infants of more than 2 500 g birthweight. Antepartum fetal deaths were the second largest group, comprising 20 % of deaths. Sixty percent of the infants in this group weighed less than 2 500 g at birth. Major malformations were responsible for few perinatal deaths in Jamaica. This simple classification is important as it focusses attention on details of labour and delivery that may require change and is useful in planning future delivery of obstetric and neonatal care.     

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.     

ECG changes in asphyxia neonatorum

Twenty five asphyxiated neonates had ECG changes consistent with degree of asphyxia. Equivocal changes were found in mild asphyxia and changes suggestive of myocardial infarction were seen with severe asphyxia. In most cases, the changes reverted to normal within two weeks signifying great ability of the neonatal heart to withstand hypoxic insult. Four babies with severe asphyxia having ECG changes suggestive of acute myocardial infarction expired within 48 hours of birth.     

Gliosis in neonatal SUDI cases

Aim: To review sudden unexpected infant deaths (SUDI) in the first 28 days of life referred to a Coronial Perinatal Forensic Pathology Service over a 10‐year period from 2000 to 2009. Methods: Cases were collected from mortuary records, and a retrospective review of autopsy reports and other available infant records was undertaken. Results: Twenty‐four neonatal SUDI were reviewed. For eight infants, a diagnosis was made at autopsy. For the remaining 16 infants, 14 (87.5%) were bedsharing at the time of death. Maori infants and those living in deprived neighbourhoods were over‐represented. Only two infants were preterm, and four were growth‐restricted. At post‐mortem, white matter gliosis was found in 10 of the 16 (62.5%) unexplained SUDI cases. Conclusion: Sudden unexpected infant deaths occur in the first month of life in association with bedsharing. Gliosis may be an important associated risk factor, and its presence indicates a previous insult of prenatal onset.     

Neonatal mortality in France: usefulness of a neonatal death certificate]

A neonatal death certificate was introduced in France in 1997. It provides detailed data on the causes of death and the characteristics of newborn, birth and parents. Our aim was to describe the new results of this certificate. METHOD: All deaths in 1999 in the first 27 days of life were included (N=2036). Certificates were analysed using the usual process, especially following the International Classification of Diseases. RESULTS: The neonatal death certificate was used for 87% of deaths. The proportion of documented items was 96% for gestational age and birthweight, 87% for maternal age and parity and 70% for maternal occupation. Almost three quarters of the deaths occurred in the first 6 days (36.9% in the first 24 hours and 35.1% between one and six days). 30.5% of the died infants were born before 27 weeks of gestation and 36.5% between 27 and 36 weeks. A shift in medical care was observed at 26 weeks, with an increase in caesarean sections before labour and newborn referrals. In all, 63.3% of neonatal deaths were due to perinatal conditions, and 27.9% to congenital anomalies. The proportion of deaths explained by congenital anomalies was higher for longer gestational age: 14% of deaths between 25 and 28 weeks of gestation vs 38 to 43% between 33 and 42 weeks. CONCLUSION: The neonatal death certificate was well accepted; however the data on detailed causes of death and parent's characteristics were insufficient. Analysis of the circumstances and the causes of death is facilitated with the neonatal death certificate and it will be developped in the future.     

Is serum troponin T a useful marker of myocardial damage in newborn infants with perinatal asphyxia?

AIM: To assess the correlation of echocardiographic signs of myocardial damage to serum cardiac troponin T (cTnT) concentrations in newborn infants with perinatal asphyxia. METHODS: Electocardiograms (ECG) and echocardiograms (Echo) were obtained during the first 24 h of life from 29 asphyxiated and 30 control infants and correlated with cTnT concentrations. The echocardiographic parameters included systolic ventricular performance, preload, afterload, diastolic function, stroke volume (SV), left ventricular output (LVO), hyperechogenity of the papillary muscles and insufficiency of the atrioventricular valves. RESULTS: LVO and SV were lower but CTnT were significantly higher in asphyxiated than in control infants: 0.15 (010-0.23) vs. 0.05 (0.02-0.13), p < 0.001). Asphyxiated infants with signs of myocardial damage were associated with significantly higher cTnT than those without, 0.20 (0.11-0.28) and 0.11 (0.05-0.14 ug/L), p = 0.04. CONCLUSION: Cardiac troponin may prove to be valuable in evaluating myocardial damage in birth asphyxia. However, the degree of prematurity may complicate the assessment.     

Effect of birth asphyxia on serum calcium levels in neonates

Serum calcium and phosphorus levels were measured at birth, 6 hours, 24 hours, and on 5th day of life in 35 neonates with birth asphyxia (one-minute Apgar score of 6 or less), and in 37 neonates without asphyxia (one-minute Apgar score of 7 or more). Infants were divided into three groups: FT-AGA (n=30, asphyxia=15), FT-IUGR (n=20, asphyxia=10) and PT-AGA (n=22, asphyxia=10). Asphyxiated infants-FT-AGA as well as FT-IUGR-had significantly lower serum calcium levels than control infants during each of the time period studied. In PT-AGA infants with asphyxia, the serum calcium was significantly low only on 5th day of life. Lack of calcium intake, and hyperphosphatemia were identified as possible risk factors for low serum calcium in asphyxiated infants. No change in serum calcium levels was found in bicarbonatetreated asphyxiated infants in comparison to those who did not receive sodium bicarbonate. In view of the high incidence of low serum calcium in asphyxiated infants, serial monitoring of serum calcium levels is recommended in these infants.     

脑电图背景活动对窒息足月新生儿预后评估的研究

目的：新生儿期最常见的脑损伤疾病为新生儿重度窒息后的缺氧缺血性脑病（HIE）,可遗留神经系统后遗症。目前对新生儿HIE预后的判断方法除考虑异常围生期因素、常规神经系统体格检查外,只能依赖于颅内超声、CT、MRI等影像学方法,这些方法主要建立在解剖结构改变基础之上,而脑电图则能发现早期的脑功能异常。该研究的目的是通过对足月窒息新生儿脑电图背景活动的研究,检测并评估与窒息新生儿预后相关的参数,并根据数理原理得出并证明这些参数对预后判断的价值。方法：对80名生后24 h至日龄<8 d的足月新生儿（对照组31人,窒息组49人）脑电图进行平行对照的前瞻性分析,并在出院后对窒息组患儿进行6~12个月的随访。结果：①窒息患儿交替性脑电活动期平均阵发性放电间期延长,振幅降低,阵发性活动、异常尖波频率出现率和睡眠周期循环障碍的发生率增加。②对窒息患儿预后判断有重要意义的参数为胎龄、出生体重、脑电活动振幅均值、睡眠循环障碍、影像学异常改变、HIE分级。③出生24 h后脑电图仍表现为平坦波或平坦波伴大量异常放电患儿预后极差。结论：脑电图背景活动是足月窒息新生儿预后判断的有效工具,如结合患儿脑电图背景活动及其胎龄、出生体重、影像学检查、HIE分级等临床指标,可使预后判断更为准确。［中国当代儿科杂志,2007,9（5）：425-428］     

新生儿窒息与宫内巨细胞病毒感染22例

目的探讨新生儿窒息与宫内巨细胞病毒（CMV）感染的关系。方法对窒息新生儿在生后1wk内进行血清CMV特异抗体IgM、IgC检测，部分病人同时送检脑脊液、尿、胃液找巨细胞包涵体、死亡病例进行病理检查。结果22例窒息新生儿中宫内CMV感染者16例，占72.73%．其力3例死亡。死亡病例经病理检查证实为全身性CMV感染。结论宫内CMV感染为窒息的原因之一。     

Clinical Evaluation of the Pathogenesis of Neonatal Asphyxia

The perinatal mortality rate in Japan decreased from 16.8 per 1000 live-births in 1964 to 4.5. in 1980, and the early neonatal mortality rate from 8.1 in 1964 to 1.1 in 1980. These decreases are mainly due to the improvement in prognosis of premature infants. The incidence of neonatal asphyxia in mature infants also decreased from 8.8% in 1967–68 to 5.1% in 1979–80. Fetal distress, breech delivery and Caesarean section were the major causes of neonatal asphyxia. Early detection of fetal distress and appropriate care decreased both the incidence of neonatal asphyxia and the neurological signs even in severely asphyxiated infants.     

Comparison of serum cardiac troponin T and creatine kinase MB isoenzyme mass concentrations in asphyxiated term infants during the first 48 h of life

OBJECTIVE: This prospective study aimed to compare serum creatine kinase MB isoenzyme (CK-MB) mass concentrations and cardiac troponin T (cTnT) concentrations during the first 48 h of life in asphyxiated term infants. METHODS: Serum cTnT and CK-MB mass concentrations of 50 term infants with clinical features of perinatal asphyxia were measured at birth and at 12, 24 and 48 h of age by chemiluminescence immunoassay. These infants were followed up until discharge or death. Cord blood CK-MB and cTnT concentrations of 50 healthy term infants were also assayed. RESULTS: At birth, asphyxiated infants had significantly higher concentrations of cTnT and CK-MB than controls (P < 0.0001). Serum cTnT of asphyxiated infants with low ejection fraction <60% was significantly higher at 12 and 24 h than those with normal ejection fraction (P < 0.05). Asphyxiated infants with congestive cardiac failure had significantly higher serum cTnT concentration during the first 48 h of life than those without congestive cardiac failure (P or= 0.1). CONCLUSION: Unlike CK-MB, serum cTnT concentrations are significantly higher in asphyxiated infants who die or develop cardiac dysfunction.     

2005年中南地区产科新生儿流行病学调查

目的：通过对我国中南地区城市医院分娩的新生儿的调查,了解我国中南地区新生儿出生情况。方法：抽取我国中南地区的23所医院进行调查。回顾性调查了2005年1月1日至同年12月31日期间出生的产科住院新生儿15582名。结果：（1）新生儿男女性别比为1.16∶1;（2）早产儿发生率为8.11%;（3）极低出生体重儿发生率为0.73%;（4）分娩方式：自然分娩占57.52%,剖宫产占40.82%（其中因社会因素剖宫产占29.91%）,其他产式占1.66%;（5）新生儿窒息发生率为3.78%,其中重度窒息占0.75 %;（6）新生儿死亡率为0.55%,其中早产儿死亡率为5.56%。结论：（1）我国中南地区早产儿发生率和新生儿窒息发生率均较高;（2）我国中南地区剖宫产比例较高,尤其是社会因素所占的比例过高。     

Plasma thrombomodulin level in newborn infants with and without perinatal asphyxia

To determine whether vascular endothelial damage occurs in neonates with asphyxia, we examined the plasma thrombomodulin level at birth in infants with and without asphyxia. The plasma thrombomodulin concentration in 11 asphyxiated infants was significantly elevated compared with that in 48 infants without asphyxia (38.1 vs 27.0 μg/l, p < 0.0001). The plasma thrombomodulin-to-serum creatinine ratio was also significantly elevated (0.62 vs 0.48 μg/μmol, p = 0.0005). The plasma thrombomodulin concentration and the plasma thrombomodulin-to-serum creatinine ratio in infants without asphyxia did not differ between the two types of delivery: normal vaginal delivery and elective caesarean section. Stepwise regression analysis showed the serum D-dimer concentration, plasma pH and serum creatinine concentration were significant independent variables for plasma thrombomodulin concentration, whereas base deficit, platelet count, fibrinogen concentrations and antithrombin III activity were not. Our data suggest that vascular endothelial damage might occur in asphyxiated infants.     

Why hypothermia in neonatal hypoxic ischemic encephalopathy?

The incidence of asphyxiated full-term infants is still high in both high income and developing countries. In up to 80 percent of infants, moderate to severe birth asphyxia results in long-term neurological sequelae. Many years of experimental work and a limited data on hypoxic-ischemic neonates have supported the hypothesis that hypothermia after the primary insult induces permanent neuroprotection. In this mini overview, we attempt to update pediatricians in this aspect and raise the following: Will the future treatment include hypothermia along with the conventional and or other promising drugs affecting different aspects of the hypoxia-ischemia?