Auditory event-related potentials are related to cognition at preschool age after very preterm birth Hemisphere Differences in Speech-Sound Event-Related Potentials in Intensive Care Neonates Effects of Early Intervention on Cognitive Function of Low Birth Weight Preterm Infants, Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm Patterned feeding experience for preterm infants: study protocol for a randomized controlled trial Cognitive development in low risk preterm infants at 3–4 years of life Diagnostic and Predictive Value of Auditory Evoked Responses in Preterm Infants: II. Auditory Evoked Responses Effect of Early Prophylactic High-Dose Recombinant Human Erythropoietin in Very Preterm Infants on Neurodevelopmental Outcome at 2 Years: A Randomized Clinical Trial. The discrepancy between maturation of visual-evoked potentials and cognitive outcome at five years in very preterm infants with and without hemodynamic signs of fetal brain-sparing. Neonatal pain, parenting stress and interaction, in relation to cognitive and motor development at 8 and 18months in preterm infants Psychological functioning and health-related quality of life in adulthood after preterm birth. Early home intervention with low-birth-weight infants and their parents. Abnormal sensory reactivity in preterm infants during the first year correlates with adverse neurodevelopmental outcomes at 2 years of age Neonatal head ultrasound abnormalities in preterm infants and adolescent psychiatric disorders. Association of early versus late caffeine administration on neonatal outcomes in very preterm neonates Improved Cognitive Development Among Preterm Infants Attributable to Early Supplementation of Human Milk With Docosahexaenoic Acid and Arachidonic Acid Hippocampal Volume and Everyday Memory in Children of Very Low Birth Weight Neurophysiologic correlates of deficient phonological representations and object naming in prematurely born children Impact of oral probiotics on neurodevelopmental outcomes in preterm infants Early intervention for low birth weight, preterm infants: the role of negative emotionality in the specification of effects. Randomised trial of parental support for families with very preterm children: outcome at 5 years The Etiology and Outcome of Cerebral Ventriculomegaly at Term in Very Low Birth Weight Preterm Infants Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia.
Background : Auditory event-related potentials ( AERP ) are neurophysiological correlates of sound perception and cognitive processes . Our aim was to study in very preterm born children at preschool age if AERP correlate with cognitive outcome . Methods : Seventy children ( mean ± SD gestational age 27.4 ± 1.9 wk , birth weight 996 ± 288 g ) were investigated at age 4.3–5.3 y with psychological testing ( WPPSI-R , four subtests of NEPSY ) . Electroencephalogram was recorded while they listened to a repeated st and ard tone , r and omly replaced by one of three deviants .  Latencies and amplitudes for AERP components and mean amplitudes in successive 50-ms AERP time windows were measured . Results : Better cognitive test results and higher gestational age correlated with shorter P1 latencies and more positive mean amplitudes 150–500 ms after stimulus change onset . Neonatal brain damage was associated with a negative displacement of AERP curves . Neonatal morbidity had an impact on earlier time windows while gestational age and brain damage on both early and later time windows . Conclusion : AERP measures were associated with cognitive outcome . Neonatal morbidity mainly affects early cortical auditory encoding , while immaturity and brain damage additionally influence higher cortical functions of auditory perception and distraction . Perinatal auditory environment might play a role in development of auditory processing Neurodevelopmental delays in intensive care neonates are common but difficult to predict . In children , hemisphere differences in cortical processing of speech are predictive of cognitive performance . We hypothesized that hemisphere differences in auditory event-related potentials in intensive care neonates are predictive of neurodevelopment in infancy , even in those born preterm .  Event-related potentials to speech sounds were prospect ively recorded in 57 infants ( gestational age 24 - 40 weeks ) prior to discharge . The Developmental Assessment of Young Children was performed at 6 and 12 months . Hemisphere differences in mean amplitudes increased with postnatal age ( P < .01 ) but not with gestational age . Greater hemisphere differences were associated with improved communication and cognitive scores at 6 and 12 months , but decreased in significance at 12 months after adjusting for socioeconomic and clinical factors . Auditory cortical responses can be used in intensive care neonates to help identify infants at higher risk for delays in infancy The Infant Health and Development Program is a r and omized clinical trial to test the efficacy of educational and family support services and pediatric follow-up , offered during the first 3 years of life , in reducing the incidence of developmental delay in low birth weight preterm infants at eight clinical sites ( N = 985 ) . It was hypothesized that larger intervention effects would be found for the domains in which low birth weight preterm infants are known to have problems , specifically visual-motor and spatial skills and receptive language skills . These analyses explore the effects of the Infant Health and Development Program on different domains of cognitive functioning . Cognitive domains are identified by means of factor analysis of the intelligence tests used at 12 , 24 , and 36 months ( Bayley Scales of Infant Development ( including the Mental and Motor scales ) at 12 and 24 months ; the Stanford-Binet , Peabody Picture Vocabulary Test , and Beery Test of Visual Motor Intergration at 36 months ) . Our results reveal that , although intervention benefits accrue across cognitive domains at 24 and 36 months , gains are most pronounced for receptive language and visual-motor and spatial skills BACKGROUND Infants born very preterm ( <33 weeks ) are at increased risk of neurocognitive deficits . Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography , but little is known of their later function . We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence . METHODS A cohort of 105 infants born before 33 weeks of gestation in 1979 - 80 had ultrasonographic scans at University College Hospital , London , and were prospect ively examined at 1 , 4 , and 8 years . At age 14 - 15 years , 72 of those who remained in UK ( cases ) and 21 age-matched full-term controls underwent brain magnetic resonance imaging ( MRI ) , as well as neurological , cognitive , and behavioural assessment . MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status . FINDINGS Of the 72 cases , 40 had unequivocally abnormal MRI and 15 had equivocal scans . Of the 21 controls , one had abnormal and five equivocal MRI . Abnormalities of ventricles , corpus callosum , and white matter were especially common in cases . More brain lesions were identified by MRI than by neonatal ultrasonography . The cases had significantly more reading , adjustment , and neurological impairments than controls , but their behaviour was significantly related to MRI abnormality . INTERPRETATION Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence , and more than half have abnormal MRI brain scans Background Neurobehavioral disabilities occur in 5–15 % of preterm infants with an estimated 50–70 % of very low birth weight preterm infants experiencing later dysfunction , including cognitive , behavioral , and social delays that often persist into adulthood . Factors implicated in poor neurobehavioral and developmental outcomes are hospitalization in the neonatal intensive care unit ( NICU ) and inconsistent caregiving patterns . Although much underlying brain damage occurs in utero or shortly after birth , neuroprotective strategies can stop lesions from progressing , particularly when these strategies are used during the most sensitive periods of neural plasticity occurring months before term age . The purpose of this r and omized trial is to test the effect of a patterned feeding experience on preterm infants ’ neurobehavioral organization and development , cognitive function , and clinical outcomes . Methods This trial uses an experimental , longitudinal , 2-group design with 120 preterm infants . Infants are enrolled within the first week of life and r and omized to an experimental group receiving a patterned feeding experience from the first gavage feeding through discharge or to a control group receiving usual feeding care experience . The intervention involves a continuity of tactile experiences associated with feeding to train and build neuronal networks supportive of normal infant feeding experience . Primary outcomes are neurobehavioral organization as measured by Neurobehavioral Assessment of the Preterm Infant at 3 time points : the transition to oral feedings , NICU discharge , and 2 months corrected age . Secondary aims are cognitive function measured using the Bayley Scales of Infant and Toddler Development , Third Edition at 6 months corrected age , neurobehavioral development ( sucking organization , feeding performance , and heart rate variability ) , and clinical outcomes ( length of NICU stay and time to full oral feeding ) . The potential effects of demographic and biobehavioral factors ( perinatal events and conditions of maternal or fetal/newborn origin and immunologic and genetic biomarkers ) on the outcome variables will also be considered . Discussion Theoretically , the intervention provided at a critical time in neurologic system development and associated with a recurring event ( feeding ) should enhance neural connections that may be important for later development , particularly language and other cognitive and neurobehavioral organization skills . Trial registration NCT01577615 11 April 2012 Background : Major neurological h and icaps and neuropsychological disturbances are more common in ex-preterm children than their counterparts born at term . Objective : To establish in a prospect i ve study whether a characteristic neuropsychological profile exists in ex-preterm children who do not exhibit neurodevelopmental deficits on routine clinical examination . Methods : Thirty intellectually normal children born preterm ( 30–34 weeks gestation ) without major neurological disabilities and a control group of term children matched for age , sex , and parental educational and occupational status were assessed at 3–4 years of age to obtain a complete neuropsychological profile . Intellectual ability , language comprehension and expression , perceptual and visual motor function , working memory , and attention and behavioural problems were investigated . Results : Even in the absence of major neurological signs , children born preterm achieved lower mean scores than controls on the Stanford-Binet intelligence scale ( 110.8 v 121 , p<0.001 ) , visual perception test ( 33.8 v 42.7 , p<0.001 ) , visual motor integration test ( 42.6 v 47.4 , p = 0.049 ) , memory for location test ( 8.4 v 9.5 , p = 0.007 ) , sustained attention test ( 41.6 v 51.5 , p = 0.009 ) , and the picture vocabulary test ( 33.3 v 44.7 , p = 0.021 ) . Conclusions : Neuropsychological abnormalities can be detected early in childhood in apparently normal ex-preterm children and are consistent with a growing body of evidence that prematurity may be associated with long term neuropsychological morbidity in childhood and adolescence In this study , the diagnostic and predictive value of brainstem , middle latency , and cortical auditory evoked responses ( BMC -AERs ) obtained in the neonatal period in 81 preterm infants was assessed in relation to neurodevelopmental outcome .  The preterm infants were neonatally classified according to risk category and gestational age . The  BMC -AERs  were analyzed with respect to detectability , latencies , and amplitudes as well as derived latency and amplitude measures . At 5 y of age the neurodevelopmental outcome was assessed from neurologic and neuropsychologic evaluations . The results showed that BMC -AER differences mainly correlated with risk category ( low risk/high risk ) and to some extent with degree of prematurity . In view of these findings the degree of prematurity and the effect of risk category have to be taken into account , when BMC -AERs are applied in the preterm period to predict neurodevelopmental outcome . In this study the BMC -AERs for infants with abnormal neurodevelopmental outcome were scarcely distinguishable from the BMC -AERs for infants with normal neurodevelopmental outcome . Thus far , this and previous reports have indicated that BMC -AERs in preterm infants are useful in maturational studies and with infants showing symptoms related to lesions or dysfunction of the peripheral and /or central auditory system . For predicting neurodevelopmental outcome in preterm infants , BMC -AERs are of limited clinical value IMPORTANCE Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay . Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies . OBJECTIVE To determine whether prophylactic early high-dose recombinant human erythropoietin ( rhEPO ) in preterm infants improves neurodevelopmental outcome at 2 years ' corrected age . DESIGN , SETTING , AND PARTICIPANTS Preterm infants born between 26 weeks 0 days ' and 31 weeks 6 days ' gestation were enrolled in a r and omized , double-blind , placebo-controlled , multicenter trial in Switzerl and between 2005 and 2012 . Neurodevelopmental assessment s at age 2 years were completed in 2014 . INTERVENTIONS Participants were r and omly assigned to receive either rhEPO ( 3000 IU/kg ) or placebo ( isotonic saline , 0.9 % ) intravenously within 3 hours , at 12 to 18 hours , and at 36 to 42 hours after birth . MAIN OUTCOMES AND MEASURES Primary outcome was cognitive development assessed with the Mental Development Index ( MDI ; norm , 100 [ SD , 15 ] ; higher values indicate better function ) of the Bayley Scales of Infant Development , second edition ( BSID-II ) at 2 years corrected age . The minimal clinical ly important difference between groups was 5 points ( 0.3 SD ) . Secondary outcomes were motor development ( assessed with the Psychomotor Development Index ) , cerebral palsy , hearing or visual impairment , and anthropometric growth parameters . RESULTS Among 448 preterm infants r and omized ( mean gestational age , 29.0 [ range , 26.0 - 30.9 ] weeks ; 264 [ 59 % ] female ; mean birth weight , 1210 [ range , 490 - 2290 ] g ) , 228 were r and omized to rhEPO and 220 to placebo .  Neurodevelopmental outcome data were available for 365 ( 81 % ) at a mean age of 23.6 months . In an intention-to-treat analysis , mean MDI was not statistically significantly different between the rhEPO group ( 93.5 [ SD , 16.0 ] [ 95 % CI , 91.2 to 95.8 ] ) and the placebo group ( 94.5 [ SD , 17.8 ] [ 95 % CI , 90.8 to 98.5 ] ) ( difference , -1.0 [ 95 % CI , -4.5 to 2.5 ] ; P = .56 ) . No differences were found between groups in the secondary outcomes . CONCLUSIONS AND RELEVANCE Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection , compared with infants who received placebo , there were no statistically significant differences in neurodevelopmental outcomes at 2 years . Follow-up for cognitive and physical problems that may not become evident until later in life is required . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00413946 OBJECTIVE After intrauterine growth restriction we found at the age of 6 months an acceleration of neurophysiologic maturation . However , at later ages impaired cognitive outcome has been reported . Therefore , we investigated in children with and without fetal hemodynamic adaptation to intrauterine growth restriction whether the accelerated neurophysiologic maturation in infancy might be associated with impaired cognitive outcome at preschool age . DESIGN At 5 years of age cognitive function was assessed using the Revision of the Amsterdam Children 's Intelligence Test in 73 preterm infants ( 26 - 33 weeks ) who were prospect ively followed from the antenatal period up to the age of 5 years . Maternal educational level was used as a background variable to estimate the confounding effects of socioeconomic status on cognitive function . Fetal Doppler studies were performed and the umbilical artery pulsatility index ( PI ) divided by the middle cerebral artery PI ratio ( U/C ratio ) was calculated . A U/C ratio > 0.725 was considered as an indication of fetal cerebral hemodynamic adaptation to a compromised placental perfusion , ie , fetal brain-sparing . Visual-evoked potentials ( VEPs ) were recorded at 6 months and 1 year of age . In addition , data on neurologic status at 3 years were available . RESULTS Mean IQ score was significantly lower for children born with a raised U/C ratio ( 87 + /- 16 ) compared with children with a normal U/C ratio ( 96 + /- 17 ) . VEP latencies decreased significantly in infants with a normal U/C ratio , whereas no decrease was found in infants with a raised U/C ratio . Variables contributing significantly to the variance of cognitive function were : U/C group , VEP latency maturation , level of maternal education , and neurodevelopmental outcome at 3 years . The linear regression model explained 33 % of the variance in cognitive function . CONCLUSIONS Both being born with a raised U/C ratio and an acceleration of VEP latencies are negatively associated with cognitive outcome at 5 years of age . Fetal brain-sparing , although a seemingly beneficial adaptive mechanism for intact neurologic survival , is , however , later associated with a poorer cognitive outcome ABSTRACT Procedural pain in the neonatal intensive care unit triggers a cascade of physiological , behavioral and hormonal disruptions which may contribute to altered neurodevelopment in infants born very preterm , who undergo prolonged hospitalization at a time of physiological immaturity and rapid brain development . The aim of this study was to examine relationships between cumulative procedural pain ( number of skin‐breaking procedures from birth to term , adjusted for early illness severity and overall intravenous morphine exposure ) , and later cognitive , motor abilities and behavior in very preterm infants at 8 and 18 months corrected chronological age ( CCA ) , and further , to evaluate the extent to which parenting factors modulate these relationships over time . Participants were N = 211 infants ( n = 137 born preterm ⩽32 weeks gestational age [ GA ] and n = 74 full‐term controls ) followed prospect ively since birth . Infants with significant neonatal brain injury ( periventricular leucomalacia , grade 3 or 4 intraventricular hemorrhage ) and /or major sensori‐neural impairments , were excluded .  Poorer cognition and motor function were associated with higher number of skin‐breaking procedures , independent of early illness severity , overall intravenous morphine , and exposure to postnatal steroids . The number of skin‐breaking procedures as a marker of neonatal pain was closely related to days on mechanical ventilation . In general , greater overall exposure to intravenous morphine was associated with poorer motor development at 8 months , but not at 18 months CCA , however , specific protocol s for morphine administration were not evaluated . Lower parenting stress modulated effects of neonatal pain , only on cognitive outcome at 18 months The aim of this study was to determine if preterm birth is associated with socioeconomic status ( SES ) , psychological functioning , and health-related quality of life ( HRQoL ) in adulthood . We used prospect i ve follow-up of 192 adult offspring of mothers who took part in a r and omized controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome ( 66 born at term [ 33 males , 33 females ] 126 born preterm [ 66 males , 60 females ] ) .  Cognitive functioning was assessed using the Wechsler Abbreviated Scale of Intelligence . Working memory and attention was assessed using the Benton Visual Retention Test , the Paced Auditory Serial Addition Test , and the Brown Attention Deficit Disorder Scale . Psychiatric morbidity was assessed using the Beck Depression Inventory II , the State-Trait Anxiety Inventory , and the Schizotypy Traits Question naire . H and edness was assessed using the Edinburgh H and edness Inventory . HRQoL was assessed using the Short Form-36 Health Survey . Moderately preterm birth ( median gestation 34wks , mean birthweight 1946 g [ SD 463 g ] ) was not related to later marital status , educational attainment , SES , cognitive functioning , working memory , attention , or symptoms of anxiety or schizotypy at 31 years of age . Preterm birth was associated with fewer symptoms of depression and higher levels of satisfaction in three of the eight HRQoL domains measured ( bodily pain , general health perception , and social functioning ) . Adults who were born moderately preterm have SES , psychological functioning , and HRQoL consistent with those who were born at term . This good long-term outcome can not be extrapolated to those with early childhood disability or very low birthweights We investigated the effects of a year-long home intervention with a sample of preterm infants r and omly assigned to 1 of 3 groups : a developmental intervention , a parent-infant intervention , and a no-treatment control group . A full-term no-treatment control was also used . Both intervention approaches focused on the parent-child unit , providing training for parents to improve observational skills , emotional support , and information about community re sources . However , whereas specific tasks to facilitate the child 's development were provided in the developmental intervention group , the quality of the parent-infant interaction was the target for treatment in the other group . All infants were assessed at 4 , 8 , 12 , and 16 months of age corrected for prematurity . The results suggest that although both intervention approaches were effective in modifying some aspects of the home environment and , to a lesser degree , in improving infants ' cognitive development , the parent-infant interaction approach seemed to have the greater impact . These findings confirm previous observations regarding the cognitive development of preterm and full-term infants during the first 18 months of life and demonstrate changes in behavior and behavior styles in both pre- and full-term infants as they become older Background Sensory experience is the basis for learning in infancy . In older children , abnormal sensory reactivity is associated with behavioural and developmental disorders . We hypothesised that in preterm infants , abnormal sensory reactivity during infancy would be associated with perinatal characteristics and correlate with 2-year neurodevelopmental outcomes . Methods We conducted a prospect i ve observational study of infants with birth weight ≤1500 g using the Test of Sensory Function in Infants ( TSFI ) in the first year . Infants with gestational age ≤30 weeks were tested with the  Bayley Scales of Infant and Toddler Development III ( BSID III ) at 24 months . Results Of the 72 participants evaluated at 4–12 months corrected age ( median 8 months ) , 59 ( 82 % ) had a least one TSFI score concerning for abnormal sensory reactivity . Lower gestational age was associated with abnormal reactivity to deep pressure and vestibular stimulation ( p<0.001 ) . Poor ocular-motor control predicted worse cognitive and motor scores in early childhood ( OR 16.7 ; p=0.004 ) , but was tightly correlated to the presence of severe white matter injury . Poor adaptive motor function in response to tactile stimuli predicted worse BSID III motor ( p=0.01 ) and language scores ( p=0.04 ) at 2 years , even after adjusting for confounders . Conclusions Abnormal sensory reactivity is common in preterm infants ; is associated with immaturity at birth , severe white matter injury and lower primary caregiver education ; and predicts neurodevelopmental delays . Early identification of abnormal sensory reactivity of very preterm infants may promote parental support and education and may facilitate improved neurodevelopment CONTEXT Infants born prematurely are at risk for a perinatal encephalopathy characterized by white and gray matter injuries that affect subsequent cortical development and neural connectivity and potentially increase risk for later psychiatric disorder . OBJECTIVE To determine the relation of perinatal brain injury , as detected by neonatal head ultrasound , to psychiatric disorders in adolescents who were born prematurely . DESIGN Prospect i ve cohort . SETTING Community . PARTICIPANTS Adolescent survivors of a population -based low-birth-weight ( < 2000 g ; 96 % preterm ; born 1984 - 1987 ) cohort ( n = 1105 ) screened as neonates with serial head ultrasounds .  Neonatal head ultrasound abnormalities were categorized as either ( 1 ) germinal matrix and /or intraventricular hemorrhage or ( 2 ) parenchymal lesions and /or ventricular enlargement . Of 862 eligible survivors , 628 ( 72.9 % ) were assessed at age 16 years . The sample consisted of 458 nondisabled survivors assessed in person . Main Outcome Measure Adolescent current and lifetime psychiatric disorders assessed with parent report on the Diagnostic Interview Schedule for Children-IV . RESULTS Compared with no abnormality , germinal matrix/intraventricular hemorrhage increased risk for current major depressive disorder ( odds ratio , 2.7 ; 95 % confidence interval , 1.0 - 6.8 ) and obsessive-compulsive disorder ( 9.5 ; 3.0 - 30.1 ) . Parenchymal lesions/ventricular enlargement increased risk for current attention-deficit/hyperactivity disorder-inattentive type ( odds ratio , 7.6 ; 95 % confidence interval , 2.0 - 26.5 ) , tic disorders ( 8.4 ; 2.4 - 29.6 ) , and obsessive-compulsive disorder ( 7.6 ; 1.39 - 42.0 ) . Parenchymal lesions/ventricular enlargement were not related to lifetime attention-deficit/hyperactivity disorder-inattentive type , but all other relations were similar for lifetime disorders . Control for other early risk factors did not alter these relations . Most of these relations persisted with control for concurrent cognitive or motor problems . CONCLUSION In preterm infants , 2 distinct types of perinatal brain injury detectable with neonatal head ultrasound selectively increase risk in adolescence for psychiatric disorders in which dysfunction of subcortical-cortical circuits has been implicated Caffeine is commonly used for preterm infants with apnoea of prematurity . The caffeine for apnoea of prematurity trial ( CAP ) was launched to determine whether survival without neurodevelopmental disability at a corrected age of 18 months is improved if apnoea of prematurity is managed without methylxanthines in infants at a high risk of apnoeic attacks ( 1 ) . Infants had to be within 10 days of birth . Forty per cent of the patients assigned to caffeine  died or survived with a neurodevelopmental disability compared with 46 % assigned to placebo ( OR 0.77 , 95 % CI 0.64–0.93 ; p = 0.008 ) . Physicians were not asked to alter their own prescribing indications for caffeine . However , only 22.5 % of the neonatologists in the trial started caffeine to prevent apnoea ( 2 ) . Thus , the risk – benefit ratio of caffeine administered exclusively for prophylaxis and therefore likely earlier remains unclear . This was emphasised by Schmidt in a recent editorial ( 3 ) commenting upon a large observational cohort study that showed that early administration decreased the incidence of BPD  in their US group of NICUs ( 4 ) . This is in line with another retrospective data analysis by Taha et al. ( 5 ) . In addition , a subgroup analysis of the CAP trial demonstrated that early caffeine treatment correlated with a larger reduction in days of respiratory support compared to late caffeine ( 6 ) . In this third large-scale observational study of the Canadian Neonatal Network , Lodha et al. retrospectively investigated the effect of early versus late initiation of caffeine therapy on  neonatal short-term outcomes  of very preterm infants . The nationwide participation result ed in an impressive number of included infants . Nevertheless , there are a few comments to make . First , the diagnosis of a PDA was based on clinical signs , with or without echocardiography . However , several studies have demonstrated that echocardiograms are required for the diagnosis of a PDA in preterm infants , as clinical signs are not reliable in the first few days of life ( 7,8 ) . Second , there are imbalances between the infants of the early and those of the late treatment groups . We also suggest that some baseline characteristics should rather be declared as outcomes and /or co- interventions ( table 3 ) due to their timely relation to the intervention . The late treatment group , for example , showed a more frequent use of postnatal steroids and an increased occurrence of air leak syndromes . The differences in baseline characteristics may have result ed in an early administration of caffeine in those babies without and a late administration in those with major risk factors for adverse outcomes , such as BPD for example . Despite adjustments for known imbalances between groups , observational studies do not have the ability to completely eliminate selection bias and observational studies investigating the effect of drug treatments are prone to confounding by indication . Thirdly , information concerning the indication to start caffeine is lacking , and no information on dosages is provided . In conclusion , this is an important study , but more data from r and omised controlled trials on the optimal timing of caffeine administration are needed before introducing early prophylactic caffeine into routine clinical practice ( 9 ) OBJECTIVE . The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants . The primary end point was cognitive development at 6 months of age . METHODS . The study was a r and omized , double-blind , placebo-controlled study among 141 infants with birth weights of < 1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital ( on average , 9 weeks ) . Cognitive development was evaluated at 6 months of age by using the Ages and Stages Question naire and event-related potentials , a measure of brain correlates related to recognition memory . RESULTS . There was no difference in adverse events or growth between the 2 groups . At the 6-month follow-up evaluation , the intervention group performed better on the problem-solving subscore , compared with the control group ( 53.4 vs 49.5 points ) . There was also a nonsignificant higher total score ( 221 vs 215 points ) . The event-related potential data revealed that infants in the intervention group had significantly lower responses after the st and ard image , compared with the control group ( 8.6 vs 13.2 ) . There was no difference in responses to novel images . CONCLUSIONS . Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months Children born preterm and of very low birth weight have an increased incidence of learning difficulties , but little is known about the specific nature of their cognitive deficits and the underlying neuropathology . We hypothesized that their vulnerability to hypoxic , metabolic , and nutritional insults would lead to reduced hippocampal volumes and to deficits in memory because of the role of the hippocampus in this domain of cognition . Neuropsychological and magnetic resonance imaging methods were used to investigate this hypothesis in adolescents born preterm ( ≤30 wk gestation , n = 11 ) or full-term ( n = 8) . The preterm group had significantly smaller hippocampal volumes bilaterally , despite equivalent head size , and showed specific deficits in certain aspects of everyday memory , both on objective testing and as indicated by parental question naires . The preterm group also had a specific deficit in numeracy . The reduced hippocampal volumes and deficits in everyday memory have previously been unrecognized , but their prevalence in a group of neurologically normal children is striking OBJECTIVE The aim of this follow-up study was to evaluate the development of object naming ability and auditory processing in prematurely born children . Furthermore , we investigated whether the mismatch negativity ( MMN ) parameters at the age of 4 years correlate with the MMN parameters and naming ability at the age of 6 years . METHODS Twelve very low birth weight ( VLBW ) preterm children ( mean age 5 years 7 months ) and matched controls were studied . Object naming was measured by the Boston naming test  . Auditory event-related potentials ( ERPs ) , especially the MMN  , were recorded for Finnish syllables ( st and ard /taa/ ; deviants /ta/ and /kaa/ ) in an oddball paradigm . RESULTS VLBW preterm children scored significantly lower in the object naming test than their controls . The MMN amplitude for consonant change was significantly smaller in the preterm group compared to the controls . The MMN amplitude at the age of 4 years correlated with the MMN amplitude at the age of 6 years . Furthermore , absence of the MMN at the age of 4 years predicted naming difficulties at the age of 6 years . CONCLUSIONS VLBW preterm children with a difficulty to preattentively discriminate changes in syllables , as indexed by the diminished change detection response , MMN , seem to have sustained naming difficulty . Therefore , it is reasonable to record the MMN along with the language development from infancy , in order to identify the children at risk for language deficiencies and to provide appropriate rehabilitation Abstract Objective : The aim of the study was to evaluate the neurodevelopment outcomes of very low birth weight ( VLBW ) preterm infants supplemented with oral probiotics for the prevention of necrotizing enterocolitis ( NEC ) . Methods : A prospect i ve follow-up study was performed in a cohort of VLBW preterm infants enrolled in a single center r and omized controlled clinical trial to evaluate the efficacy of oral probiotics for the prevention of NEC . Cognitive and neuromotor developments were assessed by using the Bayley scales of infant development II . Sensory and neurological performance was evaluated by st and ard techniques . The primary outcome was neurodevelopmental impairment at 18–24 months ’ corrected age . Results : A total of 400 infants completed the trial protocol . Of the 370 infants eligible for follow-up , 249 infants ( 124 in the probiotics group and 125 in the control group ) were evaluated . There was no significant difference in any of the neurodevelopmental and sensory outcomes between the two groups . Conclusion : Oral probiotic given to VLBW infants to reduce the incidense and severity of NEC started with the first feed did not affect neuromotor , neurosensory and cognitive outcomes at 18–24 months ’ corrected age This study examined the relation of negative emotionality in infancy to child social and cognitive developmental outcomes among low birth weight ( LBW ) preterm infants participating in the Infant Health and Development Program ( IHDP ) , a comprehensive compensatory education intervention  beginning in infancy and lasting through age 3 years . In this analysis , intervention effects at age 36 months on maternal report of child behavior as assessed by the Child Behavior Checklist externalizing and internalizing scales and on intelligence as measured by the Stanford-Binet scale were largest among children characterized by higher levels of negative emotionality in infancy . Findings indicate that for LBW preterm infants characterized by negative emotionality at age 12 months the intervention was associated with a twofold decrease in the occurrence of clinical ly meaningful levels of behavior problems at age 3 years and a fourfold decrease in the occurrence of a high-risk profile in which both internalizing and externalizing scores are in the clinical ly meaningful range . The intervention was also associated with a fivefold decrease in the occurrence of IQ < or = 75 at age 3 years among children with higher levels of negative emotionality and heavier LBW ( 2001 - 2500 g ) . However , specific aspects of temperamental difficulty such as fearfulness and anger were related to internalizing and externalizing , respectively , in both the intervention and control groups . Findings are consistent with research linking negative emotionality in infancy with social and cognitive developmental outcomes in early childhood among normal birth weight infants . Results suggest the need for further attention to child temperament in early intervention research Aims : To test the effectiveness of a home based developmental education intervention in improving outcome at 5 years for very preterm infants . Methods : The Avon Premature Infant Project ( APIP ) is a r and omised controlled trial in which the parents of 284 babies born <33 weeks gestational age received a developmental education programme , a social support intervention , or st and ard care .  A term reference population was also recruited . This study reports outcomes at 5 years ( mean age 58 months 15 days ) for 187 ( 66 % ) of these children without disability . Outcomes were assessed using the British Ability Scales II for cognitive development , the Movement ABC for motor impairment , and the Child Behavior Checklist for behavioural problems . Results : Preterm infants showed poorer cognitive performance than their term peers . Mean ( SD ) general conceptual ability ( GCA ) scores were : Portage 99.2 ( 15.7 ) ; parent adviser 100.3 ( 14.8 ) ; preterm control 101.1 ( 15.0 ) ; term reference 107.2 ( 13.4 ) . There were no significant differences between preterm groups in GCA scores indicating no effect of either intervention . Similarly , there was no significant effect of intervention on behavioural or motor outcomes . Further analyses , in which outcome data were adjusted for social factors , did not reveal any differences between the three preterm groups or by subgroups classified by a range of perinatal variables . Conclusion : The small advantage shown at 2 years of age is no longer detectable at 5 years . These results question the effectiveness of early intervention in enhancing cognitive , behavioural , and motor function at 5 years Background . Despite improvements in survival data , the incidence of neurodevelopmental h and icaps in preterm infants remains high . To prevent these h and icaps , one must underst and the pathophysiology behind them . For preterm infants , cerebral ventriculomegaly ( VM ) may be associated with adverse neurodevelopmental outcome . We hypothesized that although the causes of VM are multiple , the incidence of h and icap at 4.5 years of age in preterm infants with this ultrasonographic finding at term would be high . Methods . To test this hypothesis , we provided neurodevelopmental follow-up for all 440 very low birth weight survivors of the Multicenter R and omized Indomethacin Intraventricular Hemorrhage ( IVH ) Prevention Trial . A total of 384 children ( 87 % ) were evaluated at 54 months ' corrected age ( CA ) , and 257 subjects were living in English-speaking , monolingual households and are included in the following data analysis . Results . Moderate to severe low pressure VM at term was documented in 11 ( 4 % ) of the English-speaking , monolingual survivors . High grade IVH and bronchopulmonary dysplasia ( BPD ) were both risk factors for the development of VM . Of 11 ( 45 % ) children with VM , 5 suffered grade s 3 to 4 IVH , compared with 2/246 ( 1 % ) children without VM who experienced grade s 3 to 4 IVH . Similarly , 9/11 ( 82 % ) children with VM had BPD , compared with 120/246 ( 49 % ) children without VM who had BPD . Logistic regression analysis was performed using birth weight , gestational age , gender , Apgar score at 5 minutes , BPD , sepsis , moderate to severe VM , periventricular leukomalacia , grade of IVH , and maternal education to predict IQ < 70 . Although maternal education was an important and independent predictor of adverse cognitive outcome , in this series of very low birth weight prematurely born children , VM was the most important predictor of IQ < 70 ( OR : 19.0 ; 95 % CI : 4.5 , 80.6 ) . Of children with VM , 6/11 ( 55 % ) had an IQ < 70 , compared with 31/246 ( 13 % ) of children without VM . Children with VM had significantly lower verbal and performance scores compared with children without VM . Conclusions . These data suggest that , for preterm neonates , VM at term is a consequence of the vulnerability of the developing brain . Furthermore , its presence is an important and independent predictor of adverse cognitive and motor development at 4.5 years ' CA OBJECTIVE Cognitive deficits that characterize schizophrenia are present in the prodrome , worsen with illness onset , and predict functional outcome . Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia . METHOD This 2-site double-blind r and omized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia ( mean age of 21 years ) . Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks . We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative ( MATRICS ) , symptoms , and functioning . We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement . RESULTS Auditory training subjects demonstrated significant improvements in global cognition , verbal memory , and problem solving compared with those of computer games control subjects . Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures . Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours . CONCLUSION Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia . An individual 's baseline motivational system functioning ( reward anticipation ) , and ability to engage in auditory processing speed improvement , may represent important predictors of treatment outcome . Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions
According to our findings , auditory event‐related potentials can help to predict neurodevelopmental outcome in preterms .
Both prospect i ve and cross‐sectional studies reported a relationship between AERPs and cognitive outcome .
Our results show that larger amplitudes and shorter latencies of late AERPs are related to better cognitive outcomes .
HIGHLIGHTSPreterm birth is associated with an elevated risk for neurodevelopmental deficits .
Auditory event‐related potentials can be used to assess early cognitive functioning .
This paper represents the first systematic review investigating the predictive power of AERPs on  cognition in preterms .
ABSTRACT Prematurity is a known risk factor for later cognitive deficits .
At present there are neither behavioral nor neurological tests available to detect those preterm infants who would benefit most from early interventions .
Neurophysiologic methods , and more specifically , auditory event‐related potentials ( AERPs ) are convenient tools to investigate early cognitive functioning .
However , the capability of AERPs as a prognostic factor for mental development in preterm infants remains unclear .