Neural maturation of breastfed and formula-fed infants

Background: Human milk provides infants with a full complement of all polyunsaturated fatty acids, including docosahexaenoic acid (DHA) and arachidonic acid (AA). Formula milks only contain the precursors of DHA, AA and linoleic acid, and hence formula-fed infants must synthesize their own DHA and AA. Aim: To evaluate the effect of feeding—whether breastfeeding or formula-feeding—in early infancy upon subsequent neurodevelopment and achievement of optimum brain function. Subjects and methods: The study included 53 normal, healthy infants (30 exclusively breastfed infants and 23 exclusively formula-fed infants) at the age of 1 y (±1 mo). Each infant was subjected to a full physical and neurological examination together with neurophysiological studies including flash visual evoked potential (FVEP), brainstem auditory evoked potential (BAEP) and somatosensory evoked potential (SSEP). Results: There was significant prolongation of P ₁₀₀ wave latency of FVEP in formula-fed infants, together with significant prolongation of absolute latency of waves I, III and V of BAEP in formula-fed infants compared with breastfed infants. There was significant prolongation in inter-peak latencies between cortical and Erb's components in formula-fed infants compared with breastfed infants.

Conclusion: We can conclude that VEP, BAEP and SSEP are more mature in breastfed infants relative to formula-fed infants at 1 y of age, and thus breast milk helps earlier development and maturation of some aspects of the nervous system than milk formulas.     

Effects of bilirubin on visual evoked potentials in term infants

Abstract To determine bilirubin-induced neurotoxicity, serial visual evoked potentials (VEPs) of 72 infants with neonatal hyperbilirubinaemia and 22 controls were evaluated and compared in four sessions for 8 weeks after birth. The levels of maximal serum bilirubin were found positively related to the wave latencies of first VEP. Within 8 weeks after birth, the wave latencies were significantly prolonged in infants in the severe and moderate groups than in the controls. The amplitudes of VEPs were apparently lower in severe and moderate groups than in the control group only in the 1st week after birth. At 1 year, 4 of the 18 infants in the severe group had poor motor skills and one had general hypotonia.Conclusion These results suggest that bilirubin may affect the visual pathways, and that VEP is a useful adjunct to the neurological assessment of neonatal hyperbilirubinaemia.     

Iron deficiency anemia in infancy: long-lasting effects on auditory and visual system functioning

Evoked potentials provide noninvasive measures of nerve transmission and CNS functioning. Auditory brainstem responses (ABR) and visual evoked potentials (VEP) show dramatic changes in infancy, largely as a result of progressive myelination. Because iron is required for normal myelination, pathway transmission in these sensory systems might be affected by early iron deficiency. We previously reported evidence to that effect: infants with iron-deficiency anemia (IDA) had slower transmission through the auditory brainstem pathway, uncorrected by iron therapy. To determine long-term effects, ABR and/or VEP of healthy Chilean children who were treated for IDA or were nonanemic in infancy were compared at approximately 4 y of age. Absolute latencies for all ABR waves and interpeak latencies (except I-III interval) were significantly longer in former IDA children. Longer latency was also observed for the P100 wave on VEP. The magnitude of differences was large-about 1 SD. These findings, with differences in latencies but not amplitudes, further support the hypothesis that IDA in infancy alters myelination and provide evidence that effects on transmission through the auditory and visual systems can be long lasting. Subtle changes in sensory pathway transmission might be an underlying mechanism for the derailment of other developmental aspects in early IDA.     

The role of cortical evoked responses in predicting neuromotor outcome in very preterm infants

To explore the role of posterior tibial somatosensory evoked potentials (SSEP) and flash visual evoked potentials (VEP) in the early prediction of functional brain injury, 93 infants of less than 32 weeks gestation at birth were studied. Neuromotor outcome was defined by clinical examination at the age of 2 years. SSEP, VEP and cerebral ultrasound were compared as predictors of neuromotor outcome. Posterior tibial SSEP were the most accurate single method of predicting neuromotor abnormalities with a 83% positive predictive power for cerebral palsy and a 100% predictive power for abnormal neurology, compared to 17% and 40% for cerebral ultrasound and 38% and 85% for VEP respectively. When SSEP and VEP results were concordant, the positive predictive power for cerebral palsy and abnormal neurology was 100%. Our results suggest that posterior tibial SSEP and VEP are accurate tools in the prediction of outcome in very preterm infants.     

Visual and brainstem auditory evoked potentials in children with headache

Background: Headache is a common problem in the pediatric population. The purpose of the present study was to evaluate visual evoked potentials (VEP) and brainstem auditory evoked potentials (BAEP) in children with headache. Methods: Thirty‐seven children fulfilling the International Headache Society Criteria for a diagnosis of migraine, 35 children with tension‐type headache and 40 healthy children (control group) were enrolled in the study. Results: The mean age of patients and controls was 10.4 years. P100 latency and amplitudes of migraine patients were significantly higher than children with tension‐type headache and control subjects. Children with tension‐type headache also had higher P100 latency and amplitude values than control subjects but there was no statistical difference. BAEP responses were similar between all groups. Conclusion: Measurement of VEP latency and amplitude is a valuable and reliable test for the diagnosis of migraine and can be used safely in childhood.     

Visual neurophysiological dysfunction in infants exposed to hydroxychloroquine in utero

Aim:  Hydroxychloroquine therapy during pregnancy is thought to be safe for foetuses. Normal visual function has been showed on clinical grounds in infants exposed in utero to hydroxychloroquine, but there are few visual neurophysiological data. Our study was designed to assess retina and visual pathways using electroretinogram and visual evoked potentials in a series of infants born to mothers treated by hydroxychloroquine for connective tissue diseases.
Methods:  Twenty-one infants (3–7 months of age) were consecutively examined between June 2002 and May 2007. Full-field electroretinogram was recorded by contact lens electrodes and visual evoked potentials were recorded by occipital surface electrodes using flash stimulation in mesopic condition. Analysis was focused on the amplitudes and latencies of the a - and b -waves of electroretinogram and the latency of the P ₁₀₀ component of visual evoked potentials.
Results:  Electroretinogram abnormalities were detected in six infants, associated with delayed visual evoked potentials in four of them.
Conclusion:  Early electroretinogram and visual evoked potentials testing evidenced neurophysiological visual disturbances in a subset of infants born to mothers treated by hydroxychloroquine. Systematic clinical and neurophysiological vision testing during childhood is needed to detect possible consequences of antenatal exposure to hydroxychloroquine.     

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目的通过分析不同刺激速率下的脑干听觉诱发电位变化,观察有缺氧病史的早产儿在纠正胎龄足月时的脑功能状态。方法2002年7月至2004年7月复旦大学儿科医院新生儿科收治的早产儿,缺氧组:39例,有缺氧病史,除外其它听力及脑损伤高危因素;对照组:30例,无缺氧病史,无其他听力损伤高危因素。两组于纠正胎龄37～42周时进行脑干听觉诱发电位检查,声刺激速率为21.1/s、51.1/s和91.1/s,分析Ⅰ、Ⅲ、Ⅴ波的潜伏期、振幅、峰间期等参数,进行t检验。结果在60dBnHL刺激强度下,随刺激速率增加,各组Ⅰ、Ⅲ、Ⅴ波的潜伏期、峰间期均逐渐延长,振幅下降。在常规21.1/s时,缺氧组仅表现为Ⅴ波潜伏期和Ⅲ～Ⅴ峰间期延长;随刺激速率增加,不仅上述差异更加显著,而且Ⅲ波潜伏期、Ⅴ波振幅及Ⅰ～Ⅲ、Ⅰ～Ⅴ峰间期也表现出差异。结论有缺氧病史的早产儿在纠正胎龄足月时脑干功能仍存在异常,提高刺激速率有助于异常的检出,为更好地研究新生儿脑干功能状态及发育规律提供了新的方法。     

早产儿在不同刺激速率下的脑干听觉诱发电位变化

目的：早产儿的脑干功能发育与足月儿是否存在差异,国外的研究报道并不一致,该文通过分析不同刺激速率下的脑干听觉诱发电位,比较早产儿与足月儿的脑干功能发育状态及增加刺激速率在检测脑干功能中的作用。方法：早产儿组30例,无围生期及新生儿期合并症;足月儿组38例,为健康足月儿。两组于胎龄37～42周时进行脑干听觉诱发电位检查,声刺激速率为21.1次/s、51.1次/s和91.1次/s,分析Ⅰ,Ⅲ,Ⅴ波的潜伏期和振幅,ⅠⅢ,ⅢⅤ,ⅠⅤ峰间期以及ⅢⅤ/ⅠⅢ峰间期比值。结果：在60dBnHL刺激强度下,随刺激速率增加,两组中Ⅰ,Ⅲ,Ⅴ各波的潜伏期及峰间期均逐渐延长,振幅逐渐下降,潜伏期及峰间期与刺激速率成正相关(P<0.01),振幅与速率成负相关(P<0.01)。两组比较,各频率ⅠⅤ峰间期均无差异,但随刺激速率增高,早产儿组ⅠⅢ峰间期相对缩短(P<0.05)、ⅢⅤ峰间期相对延长(P<0.01),ⅢⅤ/ⅠⅢ峰间期比值增大(P<0.001)。两组振幅无明显差别。结论：早产儿脑干听觉通路的近外周部分较近中枢部分提前发育;提高刺激速率有助于发现更多的神经生理变化,提高脑干听觉诱发电位的诊断价值。     

Cerebral Blood Flow, PaCO2 Changes, and Visual Evoked Potentials in Mechanically Ventilated, Preterm Infants

ABSTRACT. Two estimations of global cerebral blood flow (CBF) using 133-Xenon clearance were done with an interval of about one hour in 16 mechanically ventilated, newborn infants, of less than 33 weeks gestational age. In eight infants CBF was estimated just before a change in ventilator settings, and again when the Pa_co2 was stable. In the remaining eight infants small spontaneous changes in Pa_co2 occurred. The CBF-CO₂ reactivity was similar in the two groups (+67%/kPa (95% confidence interval 13–146) and 52%/kPa (24–86)) and considerably higher than the CBF-CO₂ reactivity estimated from the interindividual variation of flow and Pa_co2 (+19%/kPa (4–36)). There were no significant relations between CBF and arterial blood pressure. Flash evoked potentials (VEP) were recorded during the 133-Xenon clearances in 8 of the infants. VEP showed no relation to changes in CBF, even when the blood flow rose from the lowest levels. CBF and VEP were obtained once in 9 other infants. Among the 17 infants, the latency of the first negative wave of the VEP was not related to the CBF level. Mean CBF in the 25 infants was 12.3 ml/100 g/min (range 4.3 to 18.9), mean Pa_co2 was 4.2 kPa (range 2.3 to 6.4). Thus, CBF-CO₂ reactivity appeared to be normal in these clinically stable, mechanically ventilated, preterm infants, suggesting that their low cerebral blood flow was well regulated. The absence of a relation of CBF with VEP suggested that cerebral blood flow was not critically decreased.     

Evoked potentials for the evaluation of latent hepatic encephalopathy in pediatric liver transplant candidates

BACKGROUND: Visual evoked potentials (VEPs) and brain stem auditory evoked potentials (BAEPs) have been proposed as tools in the diagnosis of subclinical hepatic encephalopathy (HE). However, little information exists to determine their usefulness in pediatric patients. This study was undertaken to evaluate both methods in the detection of subclinical HE in pediatric liver transplant candidates. METHODS: VEPs and BAEPs were recorded in 15 pediatric liver transplant candidates with no clinical signs of HE. The wave latencies found in these examinations were then compared with those in 16 healthy controls of similar age. Laboratory data on liver function and electroencephalographic data from the patients were also recorded to examine their correlation with the evoked potentials results. RESULTS: No differences were found in the BAEP results between patients and controls. However, in the VEPs, the liver transplant candidates had significantly prolonged N1 (N75) latencies when compared with controls; no significant delay was found in the other waves. In contrast, among the children with liver disease, higher BAEP peak latencies correlated positively with electroencephalographic abnormalities, but this correlation was not observed in VEPs. CONCLUSIONS: Evoked potentials might be of use in detecting alterations related to HE in children. However, further studies are necessary to determine their sensitivity and specificity in this situation.     

Nitrous oxide analgesia for intubating preterm neonates: a pilot study

Aim: To evaluate the administration of an equimolar mixture of N₂O and O₂ for intratracheal intubation in preterm neonates with respiratory distress syndrome (RDS). Design: Prospective evaluation of N₂O/O₂ in premature neonates with RDS. Setting: Tertiary neonatal unit from March to August 2003. Patients: Twenty-six of 79 neonates admitted for RDS within 48 h of birth. Intervention: N₂O/O₂ was administered until muscle tone was suppressed. Surfactant was given intratracheally. Patients were extubated as soon as possible. Main outcome measures: The time needed for N₂O/O₂ to suppress muscle tone, an evaluation of sedation/analgesia through movements of the limbs, and indicators of stress-related haemodynamic change, all recorded by an independent observer. Results: In the 26 patients, gestational age was 30.5 (25th, 75th percentile: 30, 32) wk and median body weight was 1540 (1220, 1900) g. Postnatal age at intubation was 2 (2, 3) h. N₂O/O₂ administration time was 8 (6, 10) min (range 4-15 min). Sedation/analgesia was complete in 77% of patients. No significant differences between pre-procedure and post-procedure values were found for heart rate (p = 0.29) or mean arterial blood pressure (p = 0.13) (paired Wilcoxon test). Time needed for intubation was 30 (20, 37) s (range 10-60 s). Side effects included transient agitation (3/26) and retching (2/26). Extubation occurred 5 (5, 10) min (range 2-15 min) after surfactant instillation. Apnoeas occurred in 3/26 patients within 2 h after extubation. Two patients required reintubation to repeat surfactant administration within 24 h after extubation.

Conclusion: N₂O/O₂ may be helpful for intubation in preterm neonates. Larger randomized, double-blind studies are needed for a thorough evaluation of effectiveness and safety.     

新生儿窒息后最大长度序列脑干听觉诱发电位的检查及意义

目的：探讨最大长度序列（maximum length sequences）脑干听觉诱发电位（以下简称MLS BAEP）,对窒息新生儿早期检查判断其缺氧缺血性脑病（HIE）及程度的意义。方法：对26例正常新生儿和103例窒息新生儿于出生后3 d内分别行常规脑干听觉诱发电位（常规BAEP）和MLS BAEP检查。将103例窒息患儿,分组为无HIE组17例,轻度HIE组37例,中度HIE组31例,重度HIE组18例。所得检查波形定位分析后取I,III,V波潜伏期及振幅,I-III,III-V,I-V峰间期作为评价指标。结果：在常规BAEP和MLS BAEP中,V波潜伏期,I-III,III-V,I-V峰间期随HIE程度的加重逐渐延长的差异较明显,尤其在MLS BAEP中随声刺激速度的加快这种差异也越显著。各亚组与正常组两两比较中,轻度和/或中度HIE组的I-III,III-V峰间期在常规BAEP无差异,而在MLS BAEP中差别有统计学意义,并随声刺激速度增加统计学差异越显著。结论：MLS BAEP通过提高声刺激速度加大对听觉神经的负荷,为窒息缺氧后脑损伤的电生理检查提供了一个更敏感的方法,并对判断这种脑功能障碍有一定量化意义。     

Infantile Refsum disease: an inherited peroxisomal disorder

Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. Initially, only an accumulation of phytanic acid was thought to be present. More recent findings showed a biochemical profile very similar to that found in classical Zellweger syndrome or neonatal adrenoleukodystrophy. Morphologically typical peroxisomes were absent in the liver. All three disorders are associated with multiple peroxisomal dysfunction. Because of these similarities pertinent clinical data of our three patients are compared with those of reported patients diagnosed as having infantile Refsum disease, neonatal adrenoleukodystrophy or Zellweger syndrome who survived for several years. Attention is drawn to the difference in severity of clinical features, ranging from infantile Refsum's disease to neonatal adrenoleukodystrophy and, finally, to Zellweger syndrome.Abbreviations IRD infantile Refsum disease - ZS Zellweger syndrome - NALD neonatal adrenoleukodystrophy - ERG electroretinogram - VEP visual evoked potentials - BAEP brainstem auditory evoked potentials - SSEP somatosensory evoked potentials - ACTH adrenocorticotropin hormone - VLCFA very long chain fatty acids - THCA trihydroxycoprostanoic acid - DHCA dihydroxycoprostanoic acid - DHAP-AT acyl-CoA: dihydroxyacetone phosphate acyltransferase     

Effect of valproate and carbamazepine on visual evoked potentials in epileptic children

The effects of carbamazepine (CBZ) and sodium valproate (SV) monotherapy on visual evoked potentials (VEP) were studied in 18 epileptic children receiving CBZ and nine epileptic children receiving SV. Pattern reversal VEP were determined before the administration of antiepileptic drugs (AED) and 1 year later during which time the patients had received AED. The VEP amplitude showed no consistent changes after 1 year of CBZ and SV therapy, but VEP P-100 latencies were significantly prolonged after 1 year of CBZ therapy. We conclude that CBZ causes a slowing down of central impulse conduction and that VEP is useful to evaluate the effects of AED within the central nervous system.     

Identification of sensory neural hearing loss in very preterm infants by brainstem auditory evoked potentials.

Brainstem auditory evoked potentials were recorded in 117 newborn infants of less than 33 weeks of gestation. The potentials were absent in 10 infants (bilaterally in eight and unilaterally in two) and present in 107. By 1 year of age nine of the 10 infants with absent brainstem auditory evoked potentials were shown to have sensory neural hearing loss and required hearing aids: the remaining infant had secretory otitis media. None of the 107 infants whose auditory evoked potentials were present were found to have sensory neural hearing loss but 13 had secretory otitis media. Measurement of brainstem auditory evoked potentials is an accurate method of identifying sensory neural hearing loss in very preterm infants.     

短潜伏期体感诱发电位在慢性炎性脱髓鞘性多发性神经根神经病中的诊断作用

目的探讨短潜伏期体感诱发电位(SSEP)对慢性炎性脱髓鞘性多发性神经根神经病(CIDP)的诊断作用。方法 48例确诊或可能CIDP患儿及40例健康对照儿童进行肌电图神经传导和/或SSEP检查(健康对照仅行SSEP检查)。肌电图神经传导检查采用4道肌电图仪进行,包括至少4条运动神经和2条感觉神经;SSEP主要观察正中神经的N6(肘部电位),N13(颈髓电位),N20(皮质电位);胫神经的N8(腘窝电位),N22(腰髓电位),P39(皮质电位)。结果肌电图神经传导检测提示,48例患儿中35例运动、感觉神经均脱髓鞘,符合CIDP确诊标准;8例为感觉神经脱髓鞘,5例为轴突变性为主。40例患儿SSEP异常(未符合CIDP确诊标准的8例感觉受累患儿和5例继发轴突变性患儿的SSEP均异常),其中7例可见臂丛神经干和/或后根水平传导异常,33例同时有腰骶丛和/或后根损害。与健康对照相比,CIDP患儿N13、N22波幅潜伏期明显延长(P0.05)。结论 SSEP可用于CIDP辅助诊断,特别是对于感觉神经受累为主或继发轴突变性的CIDP患儿。     

Visual evoked potentials and dietary long chain polyunsaturated fatty acids in preterm infants.

The influence of dietary long chain polyunsaturated fatty acid (LCP) supply, and especially of docosahexaenoic acid (DHA), on evoked potential maturation, was studied in 58 healthy preterm infants using flash visual evoked potentials (VEPs), flash electroretinography (ERG), and brainstem acoustic evoked potentials (BAEPs) at 52 weeks of postconceptional age. At the same time, the fatty acid composition of red blood cell membranes was examined. The infants were fed on breast milk (n = 12), a preterm formula supplemented with LCP (PF-LCP) (n = 21), or a traditional preterm formula (PF) (n = 25). In the breast milk and PF-LCP groups the morphology and latencies of the waves that reflect the visual projecting system were similar; in the PF group the morphology was quite different and the wave latencies were significantly longer. This could mean that the maturation pattern of VEPs in preterm infants who did not receive LCP was slower. Moreover, a higher level of erythrocyte LCP, especially DHA, was found in breast milk and PF-LCP groups compared with the PF group. ERG and BAEP recordings were the same in all three groups. These results suggest that a well balanced LCP supplement in preterm formulas can positively influence the maturation of visual evoked potentials in preterm infants when breast milk is not available.     

Nutritional effects on auditory brainstem maturation in healthy term infants

OBJECTIVE: To assess the effects of dietary long chain polyunsaturated fatty acid (LCPUFA) supplementation on auditory brainstem maturation of healthy term newborns during the first 16 weeks of life by measuring brainstem auditory evoked potentials (BAEPs). DESIGN: Throughout the 16 week study period, infants in the formula A group (n = 28) were assigned to be fed exclusively with the same formula supplemented with DHA, and infants in the formula B group (n = 26) were assigned to receive only a DHA unsupplemented but otherwise similar formula. During the study period, the first 26 consecutive infants to be fed exclusively on their mother's milk for at least the first 16 weeks of life were chosen as the control group. BAEP measurements were performed twice: at the first and 16th week of age. RESULTS: There were no significant differences among the study and control groups in the BAEP measurements performed at the study entry. At 16 weeks of age, all absolute wave and interpeak latencies in the study and control groups had significantly decreased. The decreases were significantly greater in the formula A and control groups than in the formula B group. CONCLUSIONS: Infants fed on human milk or a formula supplemented with LCPUFAs during the first 16 weeks of life show more rapid BAEP maturation than infants fed on a standard formula. Although the clinical importance and long term effects of these findings remain to be determined, routine supplementation of formulas with LCPUFAs should be considered.     

Comparison of visual evoked potentials in patients with psychogenic visual disturbance and malingering

PURPOSE: To verify the efficiency and objectivity of the pattern visual evoked potential (VEP) for organic disorders of the cortical visual system. METHODS: This retrospective study evaluated VEP in 19 patients diagnosed with psychogenic visual disturbance, 7 patients with malingering, and 37 age-matched normal volunteers. Transient (3 reversals per second) and steady-state (12 reversals per second) pattern VEPs for check sizes 15' and 30', with a contrast of 80%, were recorded. RESULTS: The amplitudes of both transient and steady-state pattern VEPs were significantly increased in patients with psychogenic visual disturbance, while patients with malingering had significantly lower amplitudes. P100 peak latency was prolonged in both groups of patients. CONCLUSION: Monitoring of patients' fixation on the stimulus showed those with psychogenic visual disturbance fixated well on the stimulus, while those with malingering did not. This finding produced a VEP amplitude reduction in patients with malingering. The reason for the VEP amplitude in patients with psychogenic visual disturbance is unclear.     

Somatosensory evoked potentials predict neurologic outcome in full-term neonates with asphyxia

Objectives: To investigate the ability of somatosensory evoked potentials (SSEP) to predict neurologic outcome in term neonates with birth asphyxia.
Methodology Upper limb SSEP were performed on nine infants of 1-7 weeks of age who had perinatal asphyxia and an encephalopathy still present at 7 days of age. Comparison was made between the cranial ultrasound, electroencephalogram (EEG), SSEP and neurologic outcome at 9-36 months.
Results Normal SSEP were found in four infants, all of whom were normal on neurologic follow up at 9-12 months. Neonatal EEG performed on two out of four of these infants were also normal, while cerebral oedema was seen on cranial ultrasound in three of the four studies. No SSEP response was seen initially in three infants, all of whom had adverse outcomes (one death, two with spastic diplegia). In contrast, their neonatal EEG had shown normal background rhythms, while two of the three cranial ultrasounds revealed oedema. For two infants the initial SSEP was absent over one hemisphere and just present over the other. Both children were abnormal on follow up at 10-12 months but did not have a hemiparesis.
Conclusions Upper limb SSEP appear more sensitive than EEG or cranial ultrasounds in predicting the short term neurologic outcome of neonates with asphyxia.