Neuromotor function and school performance in 7-year-old children born as high-risk preterm infants

Neuromotor behavior was studied in 63 children at a mean age of 7 years. They were born at a gestational age less than 32 weeks and/or birthweight under 1500 g and were categorized according to their medical history in conformance with the Neonatal Medical Index (from category I to V, from few to serious complications). We included only children considered at high risk as categorized in III to V. The neuromotor behavior study focuses on different subcategories, such as hand function, quality of walking, posture, passive muscle tone, coordination, and diadochokinesia. Hand preference and/or lateralization, the presence of associated movements, and/or asymmetry were noted, as was school performance. Then gender, gestational age, birthweight, and dysmaturity were investigated as confounding factors. The outcome at 7 years was correlated with the Neonatal Medical Index and the neonatal brain ultrasonography classification. None of the children scored 100% on the combined subcategories. Nineteen children (30%) had an overall score between 75 and 99%. Significant relationships between all different subcategories were found. Lack of hand preference, poor lateralization, and male gender were related to poor overall outcome. Poor motor control was correlated to special schooling and education below age level. The Neonatal Medical Index proved to have a significant influence on total outcome and the subcategories at the age of 7 years, with the worst outcome in children formerly classified in category V. Neuromotor behavior at 7 years of age was not related to birthweight, gestational age, dysmaturity, and neonatal brain ultrasonography classification only.     

Muscle power development in preterm infants with periventricular flaring or leukomalacia in relation to outcome at 18 months

Periventricular flaring (PVF) or periventricular leukomalacia (PVL) was diagnosed by brain ultrasound during the neonatal period in 44 infants (34 males, 10 females; mean gestational age 31 weeks 2 days, SD 2 weeks 1 day) admitted between 1995 and 1997. The infants were divided into three groups according to the severity of their condition. At 0, 3, and 6 months' corrected age an age-adequate neurological examination with special emphasis on the relation between active and passive muscle power was performed and symmetry between right and left sides was assessed. Results for the whole body, as well as for the shoulders, trunk, and legs were classified as optimal, suspect, or abnormal. Motor outcome at 18 months' corrected age was graded in the same way. An overall optimal muscle power regulation was found in one infant at 0, two at 3, and one at 6 months. Suspect outcome was found at all ages in the three groups. At 0 months muscle power regulation did not differ between the three groups. At 3 and 6 months overall poor muscle power, primarily caused by poor muscle power regulation in the shoulders and trunk, was found in infants with PVL grades III or IV. At 18 months' corrected age 24 infants showed no neurological impairment, eight infants had minor impairment, and 12 infants had severe impairment, including all 10 infants categorized as having PVL grades II or IV. The best predictors of impairment at 18 months were the combined results of muscle power in the shoulders and trunk at 3 months with those of the shoulders at 6 months.     

Evaluation of serial EEG recordings and auditory brainstem responses in the early preterm infants]

EEGs were recorded serially throughout the neonatal period and auditory brainstem responses (ABRs) in the late neonatal period in 105 preterm infants with the gestational age of less than 33 weeks and birth weights of less than 1,750g in order to study the relation between abnormal findings and neurological outcome. A study of serial EEG recordings revealed that a disorganized pattern following severe depression of background EEG activities was closely associated with deep white matter injuries detected by ultrasonography and that infants showing such features are likely to suffer from cerebral palsy. On the other hand, a dysmature pattern was often observed following prolonged mild depression, although no abnormalities were apparent on ultrasonography. This EEG pattern was more often associated with mental impairment. Any findings of ABRs were not associated with adverse outcome. We conclude that serial EEG recordings during the neonatal period in preterm infants are useful in clarifying the extent and nature of brain injury as well as future developmental problems.     

Construct validity of the Infant Motor Profile: relation with prenatal,perinatal, and neonatal risk factors

Aim The Infant Motor Profile (IMP) is a qualitative assessment of motor behaviour of infants aged 3 to 18 months. The aim of this study was to investigate construct validity of the IMP through the relation of IMP scores with prenatal, perinatal, and neonatal variables, including the presence of brain pathology indicated by neonatal ultrasound imaging of the brain. Method A longitudinal prospective study was performed in a group of 30 term infants (12 females, 18 males; median gestational age 40.1wks, range 37.6–42wks) and 59 preterm infants (25 females, 34 males; median gestational age 29.7wks, range 25–34.7wks). IMP assessments were performed at (corrected) ages of 4, 6, 10, 12, and 18 months. Socio‐economic and perinatal data were collected, which, in the case of preterm infants, included information on periventricular leukomalacia and intraventricular haemorrhage based on neonatal cranial ultrasound. Data were analysed by fitting mixed‐effects models. Results Gestational age, socio‐economic status, and 5‐minute Apgar scores were significant determinants of IMP scores in the total group of infants (p<0.001, <0.002, and <0.042 respectively). In the subgroup of preterm infants, IMP scores were significantly affected by brain lesions on neonatal ultrasound (p<0.001) and by socio‐economic status (p=0.001). Interpretation The findings support the construct validity of the IMP: IMP scores are clearly associated with relevant determinants of neuromotor function.     

Risk factors for neonatal seizures in very low birthweight infants: population-based survey

The developing brain has an increased susceptibility to seizure activity, and neonatal seizures can adversely affect neurodevelopmental outcome. This study aimed to determine the incidence of neonatal seizures in very low birthweight infants and to identify perinatal and postnatal factors associated with the occurrence of clinical seizures. A population-based cohort of 6525 very low birthweight infants born from 1995 through 1999 comprised the study group. Maternal, perinatal, or postnatal variables that showed a significant association with neonatal seizures in a univariate analysis were tested by a multiple logistic regression to assess the independent effect of each variable on the risk of seizures. The overall incidence of seizures was 5.6%. Significant independent predictors of neonatal seizures were decreasing gestational age, male gender, respiratory distress syndrome, pulmonary air leak (pneumothorax and pulmonary interstitial emphysema), intraventricular hemorrhage, periventricular leukomalacia, patent ductus arteriosus, surgical ligation of patent ductus arteriosus, necrotizing enterocolitis, and surgical treatment of necrotizing enterocolitis. Neonatal seizures appear to be associated with major morbidities and surgical interventions in very low birthweight infants. Continuous electroencephalographic monitoring could be warranted in infants following surgical treatment.     

The developmental effects of an early intervention program for very low birthweight infants

We assessed the efficacy of an early intervention program (EIP) designed to promote the neonatal behavioral organization and developmental progress in infants born prematurely. The study subjects consisted of 48 very low birthweight infants (< or = 1,500 gms) who received care in NICU of Nagasaki University Hospital, Nagasaki, Japan. During 1993-1996, the experimental group (n = 30) received the NBAS (Neonatal Behavioral Assessment Scale) based intervention combined with a therapeutic program (EIP), for 44 weeks starting from 38 weeks of postmenstrual age. The control group (historical control, n = 18) received the standard medical-nursing care without EIP during 1990-1992. Developmental outcome was assessed in both groups using the NBAS examination after EIP at 44 weeks of postmenstrual age, and the Bayley Scales at 12 months corrected age. Multivariate analyses were performed to adjust for baseline variables that might be associated with the developmental outcome: sex, appropriate or light for dates infant, birthweight, gestational age, Apgar score at 1 minute, duration of intubation, and NBAS cluster score before EIP. In the NBAS examination after EIP, the experimental group achieved significantly higher scores in orientation, motor performance, state range and state regulation tasks than the control group. Furthermore, the experimental group showed significantly higher Bayley Mental and Psychomotor Developmental Indices compared with the control group. These results suggested that EIP was effective in promoting the neonatal neurobehavioral development of very low birthweight infants.     

Hand function in low-risk preterm infants: its relation to muscle power regulation

Some reterm infants show a discrepancy in muscle power often recognisable as hyperextension of trunk and shoulders. Even if there is no evident pathology involved, the hyperextension influences later hand function. In this study we assessed a group of healthy infants (N=51) at the age of 39 weeks: 32 were born preterm (and corrected for gestational age) and 19 were born at term. Both quantitative and qualitative measures of hand function were obtained. It was found that the preterm infants scored significantly lower scores in both assessments for hand function. Moreover, a significant correlation was found between the quality of hand function at the age of 39 weeks and hyperextension of the trunk at 18 weeks. Hyperextension of the trunk at 18 weeks had a high predictive value for poor hand function at 39 weeks and thus should hold implications for clinical and therapeutic management.     

Transient periventricular echodensities in preterms and neurodevelopmental outcome

Little is known about the clinical evolution and neurologic sequelae of transient periventricular echodensities in the neonatal period. The aim of our study was to assess the neurodevelopmental outcome in preterm infants with transient periventricular echodensities. Cerebral ultrasonography was performed within the first 72 hours of life on all preterms with a < or = 37 weeks' gestational age who were admitted consecutively to the Neonatal Intensive Care Unit of the University of Parma from January 2001 to December 2002. Cerebral ultrasonography was performed at least twice within the 14th postnatal day and was repeated weekly until 40 weeks' postconceptional age. Transient aspecific echodensities were defined as areas in the periventricular region brighter than the choroid plexus persisting less than 14 days. One hundred sixty-four preterm infants were selected and divided into three groups: (1) 78 preterm infants without ultrasound abnormalities, (2) 50 preterm infants with transient periventricular echodensities, and (3) 36 preterm infants with persistent echodensities. Developmental outcome was assessed at 44 weeks' postconceptional age, after 1 month from the discharge and at the corrected ages of 3, 6, 9, and 12 months using the Griffiths Mental Developmental Scale. Group 1 and 2 infants showed normal neurodevelopment in 88.5% and 94% of cases, respectively, whereas the preterm infants belonging to group 3 had a favorable outcome in 22.2% (P < .001) of cases only. In conclusion, our study demonstrates how infants with transient echodensities show a neurodevelopmental outcome that is entirely identical to infants with a steadily negative ultrasound finding.     

Changes of positron emission tomography in newborn infants at different gestational ages, and neonatal hypoxic-ischemic encephalopathy

Cerebral glucose metabolism was measured by (18)F-fluorodeoxyglucose position emission tomography in infants at different gestational ages and with neonatal hypoxic-ischemic encephalopathy. Thirty-six preterm and term infants at different gestational ages without brain injury were divided into four subgroups: ≤32 weeks (n = 4), 33-34 weeks (n = 5), 35-36 weeks (n = 12), and ≥37 weeks (n = 15). Twenty-four newborn infants with hypoxic-ischemic encephalopathy were divided into three subgroups: mild (n = 13), moderate (n = 7), and severe (n = 4). Cerebral glucose metabolism manifested a trend toward increase, and the structure of cranial (18)F-fluorodeoxyglucose positron emission tomography images became clear with increased gestational age, especially at ≥37 weeks. Uptakes of (18)F-fluorodeoxyglucose in the ≥37-week group were significantly higher than in the ≤32-week group (P < 0.01). Cerebral glucose metabolism changed significantly in neonatal hypoxic-ischemic encephalopathy, and was either unbalanced bilaterally or relatively low at all sites. Moreover, uptakes of (18)F-fluorodeoxyglucose were significantly lower in severe than in mild and medium hypoxic-ischemic encephalopathy (P < 0.05). Cerebral glucose metabolism, as measured by (18)F-fluorodeoxyglucose positron emission tomography, may prove useful for estimating brain development and injury in newborn infants, and its clinical values need further investigation.     

Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent causes of neonatal death or neurological handicaps such as cerebral palsy, mental delay, and epilepsy. Moreover, an acute consequence of HIE are neonatal seizures which can cause an additional brain damage. The neurodevelopmental outcome is known in the mild or severe cases of HIE, but in the moderate conditions the predictivity results, to date, unsatisfying. Objective: The purpose of this prospective study was to appraise the development of post-neonatal epilepsy in a cohort of term infants with moderate HIE and neonatal seizures. Methods: This study considered all newborns admitted to Neonatal Intensive Care Unit of the University of Parma between January 2000 and December 2002 for perinatal asphyxia, then followed by Neonatal Neurology Service. In all patients, neonatal variables such as type of delivery, birth weight, gestational age, Apgar scores, the need for resuscitation and assisted ventilation soon after birth, and arterial-blood pH were analyzed. Results: Ninety-two newborns were enrolled in the study because of perinatal asphyxia. Of these, 27 subjects developed mild HIE, 25 moderate, and five severe HIE. Neonatal seizures were present in 13 subjects with moderate HIE and in all newborns with severe HIE. At the last follow-up, only three infants belonging to patients with severe HIE developed epilepsy. Conclusion: Moderate HIE seems not to be related to post-neonatal epilepsy either if associated or not with neonatal seizures.     

Neonatal seizures and neonatal epileptic syndromes

The neonatal period is defined as the first 28 days of life of a term infant; for premature infants the limit of this period is 44 completed weeks of the infant's conceptional age (CA)-defined as the chronological age plus gestational age (GA) at birth. The clinical and electroencephalographic (EEG) manifestations of seizures during this period are determined primarily by the development features of the immature brain at the time of seizure onset, but are also related to the type and diversity of etiologies and risk-factors for seizures neonates may face early in life. Neonatal seizures may be strikingly different from the clinical and electrical seizures of older children and adults. In addition, findings from basic science investigations suggest that immature animals are more likely to experience seizures in response to injury than more mature animals, although the developing brain is less susceptible to seizure-induced injury.     

不同胎龄患儿颅脑损伤情况超声研究对比

目的研究超声对不同胎龄患儿颅脑损伤情况的诊断价值。方法从平煤神马医疗集团总医院2014-12—2016-12接收的新生儿中选择100例接受超声检查的患儿,分析新生儿颅脑疾病发生情况。结果 100例新生儿中不同程度颅脑损伤检出率78.0%,其中颅内出血、脑水肿、脑白质损伤、丘脑基底核损伤所占比例分别为48.71%、25.64%、21.79%、3.84%。早产组患儿发生颅内出血、脑水肿、脑白质损伤以及丘脑基底核损伤的概率分别为73.68%、80.0%、76.47%、66.67%,显著高于足月组的26.32%、20.0%、23.53%、33.33%,2组比较差异均有统计学意义(P0.05)。早产组胎龄低于34周患儿发生颅内出血、脑白质损伤、脑水肿的概率分别为39.47%、52.94%、50.0%;胎龄34~36周则分别为34.21%、23.53%、30.0%;而足月组分别为26.32%、23.53%、20.0%,不同胎龄组发生颅内出血、脑白质损伤、脑水肿的概率对比差异均有统计学意义(P0.05),颅内出血的部位和程度对比无显著差异(P0.05)。结论对新生儿颅脑疾病采取超声诊断的效果显著,值得推广使用。     

Predictive value of neonatal MRI with respect to late MRI findings and clinical outcome. A study in infants with periventricular densities on neonatal ultrasound

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.     

A power spectral analysis of the EEG in the newborns. II. The power spectral changes of the infants with neonatal asphyxia

Power spectral analysis of the EEG at the neonatal period was performed in 33 babies with an Apgar score of 6 or less 1 minute after delivery. Their gestational ages ranged from 27 to 40 weeks, and birth weight from 1,013 g to 4,416 g. They were followed up until 18 months of age. All EEGs were recorded when the babies reached to 37-41 weeks of conceptional age, and analyzed using fast Fourier transformation. The percent power in active sleep was evaluated in this study. The abnormal EEG patterns in infants with neurological damage was classified into the following groups: (1) Increase of the percent power of the delta 1 band, (2) Decrease of the percent of the power of the delta 1. On the other hand, the EEG patterns at the neonatal period in infants with normal development who suffered from neonatal asphyxia were similar to those of age-matched controls. These results suggest one of the most important factors deciding the prognosis of the brain damage is the presence of a normal percent pattern. In conclusion, power spectral analysis of EEG at the neonatal period is useful in predicting the outcome of brain damage if it is used with visual inspection.     

Neurobehavioural profile of low-birthweight infants with cystic periventricular leukomalacia

Twenty-three low-birthweight infants (17 males, six females) diagnosed with cystic periventricular leukomalacia (PVL; median gestational age 30 wks, postmenstrual age range 25 to 36 wks; median birthweight 1365 g, range 680 to 2010 g) were evaluated and compared with 209 comparison infants (117 males, 92 females; median gestational age 33 wks, postmenstrual age range 25 to 39 wks; birthweight 1771 g, range 670 to 2460 g). There were three assessment times: 36 to 38 weeks (preterm), 40 to 42 weeks (term), and 44 to 46 weeks (post-term); the Neonatal Behavioral Assessment Scale (NBAS) was used for assessment. Outcome at 2 years was assessed on the basis of a neurological examination, magnetic resonance imaging, computerized tomography, electroencephalography, and the Mental and Psychomotor Development Indices of the Bayley Scales of Infant Development. All infants in the PVL group were found to have evidence of cerebral palsy, whereas all infants in the comparison group were normally developing. Infants with PVL performed more poorly on all elements of the NBAS examination at all three assessment times compared with the comparison group. They demonstrated poorer motor control, less responsiveness to environmental stimuli, less regulatory capacity, and more abnormal reflexes compared with the comparison group. These results suggest that LBW infants with PVL show dysfunction and/or disorganization in their neurobehavioural systems in the neonatal period. Assessment of neonatal neurobehavioural characteristics using the NBAS may assist clinicians in identifying LBW infants with PVL, and in formulating plans for the developmental care of these infants.     

Congenital oligodendroglioma with initial manifestation of jaundice

Neonatal brain tumor is a rare clinical entity. The initial presentation in affected newborn infants is often subtle, nonspecific, and rarely includes focal neurologic signs. We report a 2-day-old male infant with congenital oligodendroglioma with initial manifestations of hyperbilirubinemia. Phototherapy was started immediately after admission. Because of a tense anterior fontanel and irritable crying, head ultrasonography, computed tomography, and magnetic resonance imaging were performed and revealed a heterogenous brain tumor in the left temporoparietal lobe. Craniotomy and tumor evacuation was performed, and WHO grade III anaplastic oligodendroglioma was confirmed by the pathologic studies. The patient was discharged 3 weeks later, and outpatient follow-up examination revealed a normally developed infant at 6 months of age. The cause of jaundice was thought to be secondary to tumor hemorrhage, which was not infrequent in neonatal brain tumor.     

Brain stem nuclei in sudden infant death syndrome (SIDS): volumes, neuronal numbers and positions

It has been suggested that the defect underlying the sudden infant death syndrome (SIDS) lies in brain stem nuclei involved in cardiac and respiratory function. However, most studies have not used rigorous quantitative techniques to assess brain stem nuclear volumes and neuronal numbers. We have measured the volume, neuronal numbers and position of brain stem nuclei in 11 SIDS and 11 aged-matched control infants. Using serial sagittal sections, nuclei involved in maintaining airway patency (hypoglossal, ambiguus and retro-ambiguus), heart rate (dorsal vagal) and generation of respiratory rhythm (ambiguus and dorsal vagal) were studied. No significant differences were found in nuclear volume increase with age, total neuronal number or nuclear position between SIDS and control cases. These findings support the hypothesis that the nervous system in SIDS may be normal until the final event that kills these infants.     

Identification of infants with major cognitive delay using parental report

Aim The collection of data on longer‐term neurodevelopmental outcomes within large neonatal randomized controlled trials by trained assessors can greatly increase costs and present many operational difficulties. The aim of this study was to develop a more practical alternative for identifying major cognitive delay in infants at the age of 24 months, based on parental reports. Method A sample of 476 infants (206 female, 270 male) previously diagnosed with neonatal sepsis (mean birthweight 1329g [SD 865g], mean gestational age at birth 28.7wks [SD 4.5wks]) from the International Neonatal Immunotherapy Study were assessed using the Parent Report of Children’s Abilities – Revised and the Bayley Scales of Infant Development, 2nd edition. Logistic regression was used to model the association between the risk of major cognitive delay (i.e. Bayley Scales of Infant Development Mental Development Index <55) and the Parent Report of Children’s Abilities – Revised data. Results The receiver operating characteristic curves for a number of predictive models were constructed – each achieved an area under the curve of at least 90%. The sensitivity, specificity, positive predictive value, and negative predictive value of a number of points on the receiver operating characteristic curves are presented. Interpretation The Parent Report of Children’s Abilities – Revised is a practical tool for identifying major cognitive delay in infants at 24 months.     

PREDICTORS FOR SURVIVAL AND NORMAL NEURODEVELOPMENTAL OUTCOME OF INFANTS WEIGHING LESS THAN 1001 GRAMS AT BIRTH

Between 1979 and 1981, 67 infants weighing 1000 g or less at birth were admitted to the Hammersmith Hospital Neonatal Intensive Care Unit. 29 survived the neonatal period. Low acidosis score, without a metabolic component, was the most powerful predictor of survival. Other factors were gestational age, five-minute Apgar score, the need for ventilatory support, hypoxia, hypercapnia, pneumothorax, hypotension and the presence of a larger PVH. Of the 24 survivors followed up to three years of age, 11 were optimal, nine had some neurodevelopmental deficits and three had moderate functional handicap. Only one child has cerebral palsy and global mental retardation. Five-minute Apgar score and the presence of PDA correlated with normal outcome. None of the 20 obstetrical factors examined appeared to influence either survival or neurological outcome.     

Brain maturation in the first 3 months of life,measured by electroencephalogram: A comparison between preterm and term-born infants

ObjectivePreterm infants are at risk for altered brain maturation resulting in neurodevelopmental impairments. Topographical analysis of high-density electroencephalogram during sleep matches underlying brain maturation. Using such an EEG mapping approach could identify preterm infants at risk early in life.Methods20 preterm (gestational age < 32 weeks) and 20 term-born infants (gestational age > 37 weeks) were recorded by 18-channel daytime sleep-EEG at term age (GA 40 weeks for preterm and 2–3 days after birth for term infants) and 3 months (corrected age for preterm infants).ResultsPreterm infant’s power spectrum at term age is immature, leveling off with term infants at 3 months of age. Topographical distribution of maximal power density however, reveals qualitative differences between the groups until 3 months of age. Preterm infants exhibit more temporal than central activation at term age and more occipital than central activation at 3 months of age. Moreover, being less mature at term age predicts being less mature at 3 months of age.ConclusionTopographical analysis of sleep EEG reveals changes in brain maturation between term and preterm infants early in life.SignificanceIn future, automated analysis tools using topographical power distribution could help identify preterm infants at risk early in life.