Therapeutic hypothermia for newborn infants with hypoxic–ischaemic encephalopathy

Peripartum asphyxia complicated by moderate or severe hypoxic–ischaemic encephalopathy is a devastating global health issue. A therapeutic ‘window of opportunity’ exists after resuscitation of the asphyxiated newborn and before the delayed phase of neuronal loss. Animal studies demonstrated that neuronal injury following hypoxia–ischaemia can be prevented or reduced by a mild reduction in brain temperature. Human infant pilot studies confirmed feasibility, without major adverse effects. Randomised trials and systematic reviews comprising term infants with moderate or severe encephalopathy and peripartum asphyxia have established the neuroprotective benefit of therapeutic hypothermia. Hypothermia reduces mortality or major disability to 18 months of age, as well as cerebral palsy, and neuromotor and cognitive delay. Importantly, mortality is reduced without any increase in major neurodevelopmental disability in survivors, and with only minor adverse effects. The evidence supports therapeutic hypothermia when used within strict protocols in tertiary centres to improve the outcome for term and near‐term newborns with moderate or severe hypoxic–ischaemic encephalopathy. Equally strict protocols in non‐tertiary nurseries will enable earlier initiation of hypothermia under guidance of the regional neonatal intensive care unit and transport team.     

Pharmacokinetics and dosing of arbekacin in preterm and term newborn infants

BACKGROUND: The objective of the present study was to determine pharmacokinetic variables and to characterize a new initial dosing regimen of arbekacin (ABK) for preterm and term newborn infants. PATIENTS AND METHODS: Subjects were 40 infants treated with ABK in a tertiary care neonatal unit over a period of 18 months. At birth, the infants were 23 5/7-40 0/7 weeks and weighed 530-3428 g. Serum ABK concentration was measured at two points in a course of treatment. Data were analyzed by a one-compartment model to obtain volume of distribution (Vd) and clearance (CL) of ABK. These variables were correlated with the patients' demographic and laboratory data. The new initial dosing regimen was determined based on these data. RESULTS: Sixty pairs of blood samples were taken from the infants. They were divided into three groups: preterm early (PE), gestational age (GA) < 37 weeks and postnatal age (PNA) < 28 days; preterm late (PL), GA < 37 weeks and PNA >or= 28 days; and term (T), GA >or= 37 weeks and PNA < 28 days. The Vd was 0.50 +/- 0.02, 0.48 +/- 0.04, and 0.43 +/- 0.03 L/kg, and CL was 0.59 +/- 0.04, 1.12 +/- 0.10, and 0.78 +/- 0.09 mL/min per kg (mean +/- SEM) in PE, PL, and T, respectively. The new dosing regimen is 5 mg/kg every 48 h, 5 mg/kg every 24 h, and 4 mg/kg every 24 h for PE, PL, and T, respectively. CONCLUSIONS: With the new dosing regimen, more infants achieved serum ABK levels within the optimal range than the conventional one.     

足月新生儿缺氧缺血性脑病的早期评估

目的　 探讨通过临床分度 ,新生儿行为测定 ,脑部CT对足月新生儿缺氧缺血脑病的患儿进行早期评估 ,判断预后 ,以便早期干预治疗。 方法 　按照 1996年杭州会议修定的HIE临床分度标准 ,轻度 13例 ,中度 2 7例 ,重度 14例 ,同时对其采用新生儿行为神经测定进行评估 ,头颅CT扫描检查 ,并随访至 6个月时进行发育商评估 ,以DQ≥ 90为达标水平。 结果　临床分度为轻、中度HIE者在 6个月时DQ达标率无显著差异。轻、中、重度HIE患儿在不同日龄NBNA评分有显著差异性 (P <0 0 0 1) ,临床分度越重 ,NBNA评分越低。 14d时NBNA≥ 35分和 <35分者在 6个月时DQ达标率有显著差异性 ,对判断HIE预后有较大的价值。临床分度与颅脑CT分度符合率 80 8% ,CT分度轻、中度在 6个月时DQ达标率无显著差异性 ,中与重度有显著差异性 ,与预后有关。 结论 　只有将临床分度、NBNA评分、头颅CT三者结合起来 ,综合分析才能早期准确地判断HIE的程度和预后。     

Plasma gastrin and somatostatin levels in newborn infants receiving supplementary formula feeding

Plasma gastrin and somatostatin concentrations were measured by radioimmunoassay in exclusively formula-fed infants and in breast-fed infants receiving supplementary formula during the first five postnatal days. Infants exclusively formula fed had a progressive increase in mean plasma gastrin concentration from 109±42 pmol/l (mean±SD) on the first day to 236±103 pmol/l on the fifth day after birth ( p = 0.0001). Breast-fed infants receiving supplementary formula had similar hormone concentrations as formula-fed infants of corresponding postnatal age and they also had a significant increase in hormone levels from the first to the fifth day ( p = 0.0001). A positive relationship was found between gastrin concentration and ingested milk volume: Rs = 0.51, n = 105, p = 0.0001. The high gastrin concentrations most probably reflect enhanced hormonal release from the gastrin-producing cells in response to increasing volumes of milk ingested by the infant. The mean plasma somatostatin concentration on the first day after birth was 18 ± 6 pmol/l. No significant change occurred during the first five postnatal days, independent of feeding type.     

γ-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants

γ-Aminobutyric acid (GABA) concentrations in cerebrospinal fluid (CSF) were measured in 20 neonates with various gestational and postnatal ages. These concentrations varied between 8 and 45 nmol/ml which is approximately 20–100 times the concentrations found in adults. CSF GABA concentrations tended to decrease with advancing gestational age. No apparent alterations were noted with increasing postnatal age (until 6 weeks of age). Asphyxia but not neonatal sepsis was accompanied by an increase in CSF GABA concentrations compared to respective controls.     

新生儿血、尿抗菌物质的检测及其临床意义

目的了解我国住院新生儿使用抗生素前血、尿中存在抗菌物质的情况,并探讨其对血培养结果的影响。方法用微球菌琼脂扩散法检测血、尿标本中是否存在抗菌物质,出现任何抑菌环均认为应用过抗生素。结果123例血标本中抗菌物质检测阳性73例(59.3％),34例尿标本中32例(94.1％)阳性。家长承认入院前用过抗生素者仅35例(28.4％)。临床疑有败血症40例,其中血抗菌物质检测阳性23例(57.5％)中血培养阳性仅5例(21.7％);而血抗菌物质检测阴性17例(42.5％)中血培养阳性12例(70.6％),两者比较有显著差异(P＜0.01)。瑞典新生儿8例尿抗菌物质检测均为阴性。结论抗生素在我国新生儿疾病中广泛应用,家长提供的病史并不可靠,血、尿中存在抗菌物质会降低血培养的阳性率。血、尿抗菌物质检测可作为判断血培养结果的辅助方法。     

Cerebral blood-flow velocities in predicting outcome of asphyxiated newborn infants

AIM: To evaluate the role of early (up to 12 h) changes in cerebral blood-flow (CBF) velocity in predicting the severity of hypoxic-ischaemic encephalopathy (HIE) and long-term outcome in asphyxiated term infants. METHODS: CBF velocities were investigated by colour Doppler ultrasonography in 81 healthy and 60 asphyxiated term infants at least three times during the first 5 d of life. The psychomotor development of infants was followed up to 18 mo. RESULTS: No differences in CBF velocities were found at the age of 2-6 h between infants with severe and mild-moderate HIE, mean CBF velocity [mean (95% CI of mean CBF velocity)] in anterior cerebral artery [14.9 (1.4-28.4)cm/s] and [13.9 (11.1-16.7) cm/s], respectively, and between infants with poor outcome (death or severe disability) and with normal development/mild impairments. By the age of 12 h infants with mild-moderate HIE and infants with normal development/mild impairments had decreased CBF velocity in the anterior cerebral artery, and infants with severe HIE or poor outcome had increased mean CBF velocity in anterior, medial cerebral and basilar artery compared to the control group. CONCLUSION: The value of CBF velocity changes to predict poor outcome in asphyxiated infants is low 2-6 h after asphyxia, but increases by the age of 12 ho.     

高频振荡通气治疗新生儿肺出血的临床研究

目的探讨高频振荡通气(HFOV)治疗新生儿肺出血的有效性及安全性。方法回顾性分析高频和常频通气(CMV)治疗肺出血患儿62例的临床效果,比较两组患儿的肺氧合功能、肺出血时间、住院时间、上机时间、氧疗时间、合并症及转归。结果 HFOV组治疗后1、6、12、24、48、72 h氧合指数(OI)明显低于CMV组,动脉/肺泡氧分压(a/APO2)明显高于CMV组,差异有统计学意义(P<0.05)。HFOV组呼吸机相关性肺炎(VAP)发生率明显低于CMV组(P<0.05),治愈率增高(P<0.05)。HFOV组气胸、颅内出血、消化道出血、血糖异常、败血症、肾功能损害的发生率与CMV组比较差异无统计学意义(P>0.05)。存活患儿中,HFOV组在肺出血时间、住院时间、上机时间、氧疗时间较CMV组明显缩短(P<0.05)。结论 HFOV能更好地改善肺出血患儿氧合功能,降低VAP的发生率,缩短病程,提高治愈率,与CMV组比较并不增加不良反应的发生率。     

静脉补充铁剂防治早产儿缺铁性贫血的价值

贫血是早产儿临床常见疾病之一,不仅影响患儿生长、发育,还对运动、认知学习、行为等产生不可逆影响,静脉铁剂对于无法经口服补铁或口服补铁无效的患儿是一种有效防治早产儿贫血的方法.但目前静脉铁剂用于早产儿的安全性及开始时间仍存在争议.现就静脉铁剂对于防治早产儿缺铁性贫血的有效性、安全性进行阐述.     

Cerebrospinal fluid amino acid levels in newborn infants with intracranial hemorrhage

Cerebrospinal fluid (CSF) amino acid levels including excitatory amino acids (i.e. glutamate and aspartate) in 25 preterm and 18 full-term newborn infants with no serious disease except intracranial hemorrhage (ICH) were measured. ICH was detected in 13 preterm and six full-term infants on the basis of the clinical, lumbar puncture (LP) and cranial ultrasonography (CraUSG) findings. Twelve preterm and 12 full-term infants who were neurologically healthy comprised the control group. The mean concentration of CSF amino acids did not differ between preterm and full-term infants. The CSF concentrations of taurine, threonine, glycine, alanine, valine, isoleucine, leucine, tyrosine and phenylalanine in preterm infants, and threonine, aspartic acid and alanine in full-term infants were significantly elevated in infants with ICH. These abnormalities, especially in preterm infants, are probably related to cerebral hypoxia in CSF amino acid concentrations in newborn infants with ICH.     

Short-term developmental outcome of iron prophylaxis in infants

BACKGROUND: Previous studies on the cognitive effects of iron treatment have focused on anemic or non-anemic iron-deficient infants. The effect of iron supplementation on cognitive development among iron-sufficient infants has not been studied. The aim of the present study was to examine the effect of iron supplementation on performance in the Bayley Scales of Infant Development (BSID) and anthropometric measurement in 6-month-old iron-sufficient healthy infants. METHODS: Healthy, iron-sufficient infants who were 6 months of age and were attending the Well Baby Clinic were considered for enrollment. Infants were randomly assigned to take ferrous sulfate supplementation (1 mg/kg per day) or no supplementation and were followed for 3 months. Anthropometric measurement, hematologic status and BSID were evaluated on admission and after 3 months. RESULTS: Seven infants in the intervention group and nine in the control group completed the study. No significant differences were observed in anthropometric measurements and complete blood counts between the two groups after the 3 month study period. The mean transferrin saturation (TS) level decreased significantly in the control group during the study period (from 15.3+/-2.6 to 7.8+/-5.1%; P = 0.0117), but no such reduction was seen in the intervention group. At the end of the study, the TS of the control group was found to be significantly lower than that of the intervention group (7.8+/-5.1 vs. 19.9+/-7.9%, respectively; P = 0.0033). The BSID scores of infants in both groups were within the normal range on admission and at the end of the study period. CONCLUSIONS: Short-term iron supplementation did not change developmental test scores despite the hematologic response in iron-sufficient healthy infants. The high prevelance of iron-deficiency anemia and its relationship with adverse developmental outcome suggests that prevention of iron-deficiency anemia with prophylaxis needs to be emphasized, rather than treatment.     

Serum total magnesium and ionized calcium concentrations in asphyxiated term newborn infants with hypoxic-ischaemic encephalopathy

Total magnesium, ionized calcium, potassium and sodium concentrations in mixed umbilical cord blood and venous blood serum at a median (min.-max.) age of 33 h (24-48 h) were assessed colorimetrically in 46 asphyxiated and 35 healthy term infants. Asphyxiated infants without any signs or with signs of mild hypoxic-ischaemic encephalopathy (HIE) had significantly higher, and infants with severe HIE lower umbilical cord blood serum total magnesium (mean (95%CI) 0.81 (0.75-0.87) mmol/l and 0.64 (0.47-0.87) mmol/l, respectively, p < 0.05) compared with the control group (0.72 (0.69-0.76)mmol/l). An increase in serum total magnesium in spite of normalized acid-base status in asphyxiated infants suffering from severe HIE compared with the control group infants was found by the second day of life (0.97 (0.87-1.07) mmol/l and 0.86 (0.81-0.9) mmol/l, respectively, p < 0.05). At the age of 24-48 h hypermagnesaemia (>2 SD) was discovered in 36%, hyponatremia (<2 SD) in 38%, and hypocalcaemia (<2 SD) in 23% of asphyxiated infants. Derangements (>2 SD) in at least two electrolytes by the second day of life were significantly associated with poor outcome. CONCLUSIONS: Magnesium, calcium and sodium derangements are a frequent finding in asphyxiated infants, and these abnormalities are significantly associated with poor outcome. For a better outcome prediction, the routine determination of magnesium in addition to other electrolytes in asphyxiated infants is recommended.     

Concentrations of magnesium and ionized calcium in umbilical cord blood in distressed term newborn infants with hypoxic-ischemic encephalopathy

Magnesium and ionized calcium in mixed umbilical cord blood was assessed colorimetrically in 38 distressed and 21 healthy term newborn infants. Distressed infants with a severe or moderate degree of hypoxic-ischemic encephalopathy (HIE) ( n = 8) had significantly lower ( p < 0.001 (concentrations of magnesium (0.52 ± 0.08 mmol/L) compared to the control group (0.69 ± 0.06 mmol/L). No differences in concentrations of ionized calcium between distressed and control infants were detected.     

谷氨酸和一氧化氮与新生儿缺氧缺血性脑病的关系探讨

为探讨脑脊液谷氨酸和一氧化氮（NO）水平变化在新生儿缺氧缺血性脑病（HIE）中的作用及相互关系。对24例HIE新生儿脑脊液谷氨酸和NO水平进行检测,并与8例对照组比较。结果：中、重度HIE组脑脊液谷氨酸和NO水平明显高于对照组及轻度HIE组;谷氨酸和NO呈显著正相关,提示谷氨酸和NO在新生儿HIE的发生和发展过程中具有重要意义。     

Transfusion in premature infants impairs production and/or release of red blood cells,white blood cells and platelets

OBJECTIVE: To examine whether red blood cell transfusion in infants with anaemia of prematurity alters peripheral counts of red blood cell precursors, total white blood cells and white cell differential and platelets. METHODOLOGY: In 18 consecutive stable premature infants with anaemia of prematurity, peripheral cell counts were prospectively recorded immediately before transfusion of 20 mL/kg packed red blood cells (given over 6 h), and at 48 h after completion of the transfusion. RESULTS: The median (interquartile range) haematocrit increased from 22.0% (21.3-24.0%) pre-transfusion to 37.0% (36.0-38.0%) post-transfusion (P < 0.001). Red-cell precursors decreased: median (interquartile range) reticulocytes from 3.7% (3.0-7.7%) to 3.7% (2.6-4.1%) (P = 0.03); and median (interquartile range) nucleated red blood cells from 0 G/L (0-0.2 G/L) to 0 G/L (0-0 G/L) (P = 0.03). The mean (SD) platelet count decreased from 420 G/L (154 G/L) to 313 G/L (101 G/L) (P = 0.001). The total white blood cell count and neutrophils did not change significantly; however, median (interquartile range) immature neutrophils decreased from 0.12 G/L (0.06-0.74 G/L) to 0.08 G/L (0.01-0.24 G/L) (P = 0.03). Lymphocytes, eosinophils, basophils and plasma cells remained unchanged. Monocytes increased (P = 0.01). CONCLUSIONS: Forty-eight hours after red blood cell transfusion to premature infants, there is an absolute decrease in red blood cell precursors, immature white blood cells and platelets, probably due to erythropoietin-suppression.     

Fifth day fits in the newborn

Abstract During the 1970s, there was an epidemic of neonatal convulsions occurring in apparently normal babies during the fourth and fifth days of life. This syndrome was noted in France as well as in Australia. A study was undertaken to review the King George V Hospital (KGV) experience with these 'fifth day fitters'. All cases of neonatal convulsions at KGV during the years 1972-85 were reviewed. A total of 94 cases of fifth day fits occurred during this period, accounting for 57% of all neonatal convulsions occurring during 1972-79.
The fits occurred in healthy term infants after an uncomplicated pregnancy. They appeared on the fourth and fifth days of life. The seizures lasted an average of 24 h, were refractory to drug therapy and, despite extensive investigation, no cause was found. The infants were assessed as normal at the time of discharge from hospital. Follow-up of these infants was incomplete. However, from the data available, it cannot be assumed to be a benign entity.
The 'fifth day fit' syndrome reached epidemic proportions at a number of maternity units during the 1970s. At KGV, no case has been observed since 1982.     

γ-Aminobutyric acid concentrations in the cerebrospinal fluid of newborn infants determined by high performance liquid chromatography

γ-Aminobutyric acid (GABA), a major inhibitory amino acid, has a central role in cardiorespiratory regulation. Its measurement in the cerebrospinal fluid (CSF) complements the study of neurotransmission systems. Forty-one children were studied (postnatal age <1 year). For each child, date of birth, date of sampling and current treatments were collated and their postnatal (days) and postconception (weeks) ages were calculated. CSF samples were studied using reverse phase high performance liquid chromatography (HPLC) with o -phthaldialdehyde derivation and spectro-fluorimetric measurement. A clear increase in levels of GABA was observed around 41 weeks postconception, followed by a progressive decrease, with levels stabilizing after 57 weeks post-conception. GABA-regulated neuromodulation therefore appears to be mature at 41 weeks postconception and not at birth. The data could be used in further studies investigating amino acid metabolism in relation to brain function in various neurological disorders.     

Doppler ultrasound examination of the anterior cerebral arteries of normal newborn infants: the effect of postnatal age

Twenty-four normal term infants were examined by Doppler ultrasonography of the anterior cerebral arteries at least twice in the first 5 days of life. It was found by comparison with a duplex Doppler unit that the anterior cerebral arteries could be reliably insonated using a continuous wave Doppler ultrasound probe without the concomitant use of real time ultrasound sector scanning. It was shown that the pulsatility of the velocity waveform decreased and that diastolic frequency increased over the 5 days. The significance of, and possible mechanism for, this change is discussed.     

Safety profiles of Fe2+ and Fe3+ oral preparations in the treatment of iron deficiency anemia in children

The major purpose of this study was to compare the oxidant-related toxicities of the different oral iron preparations in children with iron deficiency anemia (IDA); the second aim was to investigate the side effects of iron preparations. Seventy-two children with IDA were randomly included in the Fe²⁺ group (= 39) or the Fe³⁺ group (= 33). Some oxidizable substrates (erythrocytes malondialdehyde (MDA), urine 8-isoprostane, and basal and Cu-stimulated-oxidized LDL and antioxidant enzyme (superoxide dismutase (SOD), catalase and glutathione peroxidase) activities were evaluated at the beginning and at the 1st, 3rd, and 6th months of therapy. Side effects due to medication were recorded. While at the end of the 1st month SOD levels were significantly increased in Fe³⁺ group, at the 6th month evaluation, basal-oxidized LDL levels were significantly increased in the Fe³⁺ group, as was urine 8-isoprostane in the Fe²⁺ group. No other difference was found between two groups. In conclusion, there were minimal differences between children treated with ferric or ferrous iron in antioxidant system activities, the status of oxidizable substrates, and clinical toxicities.     

Impact of thermal vasomotor control on the heart rate variability of newborn infants

The reactivity of the periodic heart rate variability (HRV) to the thermal vasomotor control was studied during quiet sleep in a total of 20 neonates which were classified in 5 groups according to their maturity. Thermal stimulation on the peripheral skin was applied by an air blower at the rates of 5, 2.5 and 1.5 cycles/min. The oscillation of successive R-R intervals of the ECG was determined by a hybrid computer technique during thermal stimulations and compared to spontaneous HRV activity. The indices of the HRV and the total power of the periodic HRV remained unchanged during thermal stimulations. The response of the periodic HRV was selective at the spectral band corresponding to the frequency of stimulation. It was maximal at 5 cycles/min. The relative response was highly significant (P < 0.001) and it increased with increasing maturity. The state of SGA (small for gestational age) seemed to decrease the vasomotor response of the HRV. The results suggested that the thermal vasomotor control was functional already in small preterm infants and it tended to increase with increasing maturity as does the autonomic cardiac control in general.