Clinical impact of analgesic-sedative agents and peri-operative clinical status on white matter brain injury in preterm infants following surgical NEC.

BACKGROUND: The potential influence of exposure to analgesic-sedative agents (ASA) before, during, and after surgical NEC and peri-operative clinical status on white matter injury (WMI) in preterm infants has not been fully defined, and a comprehensive evaluation may inform future research and clinical interventions. METHODS: A retrospective study comparing ASA exposure before/during /after surgical NEC and peri-operative clinical status in neonates with and without WMI. RESULTS: Infants with any WMI (grade 2-4, n = 36/67, 53.7%) had a higher number of surgical procedures receiving ASA (5 [IQR: 3, 8] vs. 3 [2, 4]; p = 0.002) and had a longer duration of hypotension during their first (48.0 hours [26.0, 48.0] vs. 15.5 [6, 48]; p = 0.009) and second surgery (20 hours [0, 48h] vs. 0 [0, 22]; p = 0.017), received more hydrocortisone (35% vs.13.3%,p = 0.04) than those without any WMI. There were no differences in fentanyl/morphine/midazolam exposure before/during/after the NEC onset in the two groups.Infants with severe WMI (19/67, 28.3%, grade 3/4) had a higher incidence of AKI (P = 0.004), surgical morbidity (p = 0.047), more surgical procedures (6.5 [3, 10] vs. 4 [2, 5]; p = 0.012), and received higher mean fentanyl doses(p = 0.03) from birth until NEC onset than those without severe WMI. The univariate associations between these factors and severe WMI remained insignificant after multivariable logistic regression. CONCLUSION: Infants with WMI had more surgical procedures receiving ASA and had a longer duration of hypotension during surgeries. A large multicenter prospective study is needed to understand the full impact of ASA.

Interobserver Reliability of an MR Imaging Scoring System in Infants with Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: MR imaging has a key role in predicting neurodevelopmental outcomes following neonatal hypoxic-ischemic encephalopathy (HIE). A novel MR imaging scoring system for hypoxic-ischemic brain injury was used in our patient population with the aim of assessing interobserver variability and developing subcategories for the severity of brain injury. MATERIALS AND METHODS: We evaluated brain MR images of 252 infants who underwent hypothermia for HIE between 2014 and 2019. First, 40 infants were selected randomly to test interobserver variability. Discrepancies were identified during the assessment of the first 20 MR images. The remaining 20 MR images were scored after adjusting the scoring system. Second, we determined cutoff values for the severity of injury that were based on the percentiles of the total scores in the full cohort. RESULTS: The interobserver reliability showed excellent agreement for the total score both before (intraclass correlation coefficient = 0.96; 95% CI 0.89-0.99) and after the adjustment (intraclass correlation coefficient = 0.96; 95% CI, 0.89-0.98). The average of the differences and the agreement interval between the 2 readers decreased after the adjustment. Subcategories of brain injury were the following: We considered a total score of ≤4 (≤75%) as normal, 5-10 (76%-90%) as mild, 11-15 (91%-95%) as moderate, and >15 (>95%) as severe brain injury. The agreement on the classification of brain injury improved in the second epoch (weighted κ = 0.723 versus 0.887). CONCLUSIONS: The adjusted scoring system may lead to a higher degree of interrater agreement. The presented cutoff values may be used to determine the severity of brain injury in future clinical studies including infants with mild hypoxia-ischemia.

Early exit from neonatal therapeutic hypothermia: A single institution experience using MRI to guide decision-making.

BACKGROUND: To evaluate the feasibility of a protocol using combined magnetic resonance imaging (MRI), clinical data, and electroencephalogram (EEG) to identify neonates with mild neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH) who are eligible for "early exit". METHODS: Retrospective chart review of TH cases at a single Level III NICU over a 5-year period was used to describe the demographic, clinical, and outcome data in neonates that received early exit in contrast to 72 hour TH treatment. RESULTS: Two hundred and eight TH cases, including 18 early exit cases (9%) and 9 cases (4%) evaluated for early exit with MRI but continued on 72 hours of TH, were identified. Early exit and 72 hour treatment groups did not differ in demographics or cord gas measures, although early exit neonates had a shorter length of stay (p < 0.05). Consistent with the early exit protocol, no early exit infants had evidence of moderate or severe encephalopathy on EEG or evidence of hypoxic ischemic injury on MRI at 24 hours of life. Neurology follow up between age 1 and 18 months was available for 10 early exit infants, 8 of whom had a normal examination. CONCLUSIONS: Early MRI at 24 hours of age, alongside clinical and EEG criteria, is feasible as part of a protocol to identify neonates eligible for early exit from therapeutic hypothermia.

Longitudinal Preterm Cerebellar Volume: Perinatal and Neurodevelopmental Outcome Associations.

Impaired cerebellar development is an important determinant of adverse motor and cognitive outcomes in very preterm (VPT) infants. However, longitudinal MRI studies investigating cerebellar maturation from birth through childhood and associated neurodevelopmental outcomes are lacking. We aimed to compare cerebellar volume and growth from term-equivalent age (TEA) to 7 years between VPT (< 30 weeks' gestation or < 1250 g) and full-term children; and to assess the association between these measures, perinatal factors, and 7-year outcomes in VPT children, and whether these relationships varied by sex. In a prospective cohort study of 224 VPT and 46 full-term infants, cerebellar volumes were measured on MRI at TEA and 7 years. Useable data at either time-point were collected for 207 VPT and 43 full-term children. Cerebellar growth from TEA to 7 years was compared between VPT and full-term children. Associations with perinatal factors and 7-year outcomes were investigated in VPT children. VPT children had smaller TEA and 7-year volumes and reduced growth. Perinatal factors were associated with smaller cerebellar volume and growth between TEA and 7 years, namely, postnatal corticosteroids for TEA volume, and female sex, earlier birth gestation, white and deep nuclear gray matter injury for 7-year volume and growth. Smaller TEA and 7-year volumes, and reduced growth were associated with poorer 7-year IQ, language, and motor function, with differential relationships observed for male and female children. Our findings indicate that cerebellar growth from TEA to 7 years is impaired in VPT children and relates to early perinatal factors and 7-year outcomes.

Normative amplitude-integrated EEG measures in preterm infants.

OBJECTIVE: Assessing qualitative patterns of amplitude-integrated electroencephalography (aEEG) maturation of preterm infants requires personnel with training in interpretation and an investment of time. Quantitative algorithms provide a method for rapidly and reproducibly assessing an aEEG recording independent of provider skill level. Although there are several qualitative and quantitative normative data sets in the literature, this study provides the broadest array of quantitative aEEG measures in a carefully selected and followed cohort of preterm infants with mild or no visible injury on term-equivalent magnetic resonance imaging (MRI) and subsequently normal neurodevelopment at 2 and 7 years of age. STUDY DESIGN: A two-channel aEEG recording was obtained on days 4, 7, 14 and 28 of life for infants born ⩽30 weeks estimated gestational age. Measures of amplitude and continuity, spectral edge frequency, percentage of trace in interburst interval (IBI), IBI length and frequency counts of smooth delta waves, delta brushes and theta bursts were obtained. MRI was obtained at term-equivalent age and neurodevelopmental testing was conducted at 2 and 7 years of corrected age. RESULT: Correlations were found between increasing postmenstrual age (PMA) and decreasing maximum amplitude (R= -0.23, P=0.05), increasing minimum amplitude (R=0.46, P=0.002) and increasing spectral edge frequency (R=0.78, P=4.17 × 10(-14)). Negative correlations were noted between increasing PMA and counts of smooth delta waves (R= -0.39, P=0.001), delta brushes (R= -0.37, P=0.003) and theta bursts (R= -0.61, P=5.66 × 10(-8)). Increasing PMA was also associated with a decreased amount of time spent in the IBI (R= -0.38, P=0.001) and a shorter length of the maximum IBI (R= -0.27, P=0.03). CONCLUSION: This analysis supports a strong correlation between quantitatively determined aEEG measures and PMA, in a cohort of preterm infants with normal term-equivalent age neuroimaging and neurodevelopmental outcomes at 7 years of age, which is both predictable and reproducible. These 'normative' quantitative values support the pattern of maturation previously identified by qualitative analysis.

The impact of prenatal and neonatal infection on neurodevelopmental outcomes in very preterm infants.

OBJECTIVE: Determine the association of prenatal and neonatal infections with neurodevelopmental outcomes in very preterm infants. STUDY DESIGN: Secondary retrospective analysis of 155 very preterm infants at a single tertiary referral center. General linear or logistic regression models were used to evaluate the association with hospital factors; brain injury, growth and development; and neurobehavioral outcome. RESULT: Necrotizing enterocolitis with sepsis was associated with reduced transcerebellar diameter (38.3 vs 48.4 mm, P<0.001) and increased left ventricular diameter (12.0 vs 8.0 mm, P=0.005). Sepsis alone was associated with higher diffusivity in the left frontal lobe (1.85 vs 1.68 × 10⁻³ mm² s⁻¹, P=0.001) and right cingulum bundle (1.52 vs 1.45 × 10⁻³ mm 253 s⁻¹, P=0.002). Neurobehavioral outcomes were worse in children exposed to maternal genitourinary infection (cognitive composite: ß=-8.8, P=0.001; receptive language score: ß=-2.7, P<0.001; language composite: ß=-14.9, P<0.001) or histological chorioamnionitis (language composite: ß=-8.6, P=0.006), but not neonatal infection. CONCLUSION: Neonatal infection was associated with changes in brain structure but not with neurobehavioral outcomes, whereas the opposite pattern was observed for maternal genitourinary tract infection. These findings emphasize the potential importance of infections during pregnancy on the neurodevelopmental outcomes of preterm infants.

Maternal obesity and increased risk for autism and developmental delay among very preterm infants.

OBJECTIVE: Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years. STUDY DESIGN: Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment. RESULT: Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (ß=-9.36, (confidence interval=-15.11, -3.61), P=0.002). CONCLUSION: Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.

Factors associated with feeding difficulties in the very preterm infant.

AIM: To investigate early medical and family factors associated with later feeding risk in preterm infants. METHODS: For this longitudinal study, 136 infants born ≤30 weeks gestation were enrolled. Medical and social background factors were assessed at term equivalent age. Infants underwent magnetic resonance imaging, neurobehavioral evaluation and feeding assessment. Parent involvement in the neonatal intensive care unit was tracked, and maternal mental health was assessed at neonatal intensive care unit discharge. At age 2 years, feeding outcome was assessed using the Eating Subscale of the Infant-Toddler Social Emotional Assessment (n = 80). Associations between feeding problems at age 2 years and (i) early medical factors, (ii) neurobehavioral functioning and feeding at term equivalent age, (iii) cerebral structure and (iv) maternal mental health were investigated using regression. RESULTS: Eighteen (23%) children had feeding problems at age 2 years. Feeding problems were associated with early hypotonia (p = 0.03; ß = 0.29) and lower socio-economic status (p = 0.046; ß = -0.22). No associations were observed between early medical factors, early feeding performance, cerebral structure alterations or maternal well-being and feeding outcome. CONCLUSION: Early hypotonia may disrupt the development of oral-motor skills. Hypotonia and poor feeding also may share a common aetiology. Associations with lower socio-economic status highlight the potential influence of family background factors in feeding problems in the preterm infant.

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

BACKGROUND AND PURPOSE: WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MATERIALS AND METHODS: MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. RESULTS: In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. CONCLUSIONS: Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Parental presence and holding in the neonatal intensive care unit and associations with early neurobehavior.

OBJECTIVE: To investigate the effects of parental presence and infant holding in the neonatal intensive care unit (NICU) on neurobehavior at term equivalent. STUDY DESIGN: Prospective cohort enrolled 81 infants born 30 weeks gestation. Nurses tracked parent visitation, holding and skin-to-skin care throughout the NICU hospitalization. At term, the NICU Network Neurobehavioral Scale was administered. Associations between visitation, holding and early neurobehavior were determined using linear and logistic regression. RESULT: The mean hours per week of parent visitation was 21.33±20.88 (median=13.90; interquartile range 10.10 to 23.60). Infants were held an average of 2.29±1.47 days per week (median=2.00; interquartile range 1.20 to 3.10). Over the hospital stay, visitation hours decreased (P=0.01), while holding frequencies increased (P<0.001). More visitation was associated with better quality of movement (P=0.02), less arousal (P=0.01), less excitability (P=0.03), more lethargy (P=0.01) and more hypotonia (P<0.01). More holding was associated with improved quality of movement (P<0.01), less stress (P<0.01), less arousal (P=0.04) and less excitability (P<0.01). CONCLUSION: Infants of caregivers who were visited and held more often in the NICU had differences in early neurobehavior by term equivalent, which supports the need for and importance of early parenting in the NICU.

Identifying mothers of very preterm infants at-risk for postpartum depression and anxiety before discharge.

OBJECTIVE: We investigated whether particular demographics, maternal psychosocial and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU). STUDY DESIGN: A racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging before discharge. RESULT: Twenty percent of mothers had clinically significant levels of depression whereas 43% had moderate to severe anxiety. Being married (P<0.01), parental role alteration (P<0.01) and prolonged ventilation (P<0.05) were associated with increased depressive symptoms. No psychosocial, demographics or infant factors, including severity of brain injury, were associated with state anxiety levels. CONCLUSION: Maternal factors, such as marital status, stress from parental role alteration and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.

Impact of therapeutic hypothermia on MRI diffusion changes in neonatal encephalopathy.

OBJECTIVE: The objective of this work was to determine the impact of therapeutic hypothermia (TH) on the magnitude and time course of mean diffusivity (MD) changes following hypoxic-ischemic encephalopathy (HIE) in newborns. METHODS: Cerebral MRI scans of infants undergoing whole body TH for HIE from 2007 to 2010 were retrospectively reviewed. The data were analyzed identically to a control group of newborns with HIE previously published, prior to the development of TH. Anatomic injury was defined on T1- and T2-weighted ("late") MRI obtained after the fifth day of life. Since MD values vary regionally, the ratios of MD values for injured and normal tissue were calculated for areas of injury. Normal values were obtained from corresponding brain regions of 12 infants undergoing TH who had no injury on MRI studies. RESULTS: Twenty-three of 59 infants who underwent TH and MRI displayed cerebral injury on late MRI and were included in the study. MD ratios were decreased in all injured infants within the first 7 days of life. The return of MD to normal (pseudonormalization) occurred after the tenth day as compared to 6-8 days in the control group. Infants with severest injury demonstrated greater reduction in MD, but no difference in time to pseudonormalization. CONCLUSION: TH slows the evolution of diffusion abnormalities on MRI following HIE in term infants.

What does cyclicity on amplitude-integrated EEG mean?

In the context of amplitude-integrated electroencephalography (aEEG), the term 'sleep-wake cycling' (SWC), which is frequently used by clinicians and researchers, should be changed to 'cyclicity'. SWC is a technical term that refers to the biological pattern of alternating sleeping and waking states, which is difficult to define with only aEEG and no physical parameters. Additionally, the absence of cyclicity on aEEG is a more robust reflection of the sequence of the suppressed background patterns of an aEEG following cerebral injury or dysfunction than are sleep/wake states.

The single-patient room in the NICU: maternal and family effects.

OBJECTIVE: To explore differences in maternal factors, including visitation and holding, among premature infants cared for in single-patient rooms (SPR) compared with open-bay in the neonatal intensive care unit (NICU). STUDY DESIGN: A total of 81 premature infants were assigned to a bed space in either the open-bay area or in a SPR upon NICU admission, based on bed space and staffing availability in each area. Parent visitation and holding were tracked through term equivalent, and parents completed a comprehensive questionnaire at discharge to describe maternal health. Additional maternal and medical factors were collected from the medical record. Differences in outcome variables were investigated using linear regression. RESULT: No significant differences in gestational age at birth, initial medical severity, hours of intubation or other factors that could affect the outcome were observed across room type. Significantly more hours of visitation were observed in the first 2 weeks of life (P=0.02) and in weeks 3 and 4 (P=0.02) among infants in the SPR. More NICU stress was reported by mothers in the SPR after controlling for social support (P=0.04). CONCLUSION: Increased parent visitation is an important benefit of the SPR, however, mothers with infants in the SPR reported more stress.

High signal intensity on T2-weighted MR imaging at term-equivalent age in preterm infants does not predict 2-year neurodevelopmental outcomes.

BACKGROUND AND PURPOSE: DEHSI on T2-weighted MR imaging in preterm infants at term-equivalent age has been regarded as an unfavorable marker for neurodevelopmental outcome. The aim of this study was to examine the relationship between the presence and extent of DEHSI and neurodevelopmental outcomes. MATERIALS AND METHODS: We evaluated the MR images of 160 preterm infants at term-equivalent age. The presence of DEHSI was evaluated in separate regions and classified into 5 grades based on the extent of DEHSI. We also examined within those infants with DEHSI, whether typical signal-intensity characteristics of the posterior periventricular crossroads region were visible. Finally, ADC and FA values within the white matter were analyzed. Neurodevelopmental outcomes were assessed at 2-year corrected age with a standardized neurologic examination and the BSID-II. RESULTS: The grade of DEHSI had significant linear trends with increasing ADC and a trend toward lower FA values. However, there was no relationship between the degree of DEHSI and 2-year neurodevelopmental outcomes. In contrast, 13 infants with DEHSI who did not have visible posterior crossroads had poorer neurodevelopmental outcomes compared with infants with visible posterior crossroads. CONCLUSIONS: Although DEHSI may represent disturbances in white matter structure, as illustrated by its relationship to altered ADC and FA values, there is no relationship to short-term neurodevelopment outcome unless there are invisible posterior crossroads, representing a severe form of global high T2 signal intensity.

In vivo MRI analysis of an inflammatory injury in the developing brain.

Cerebral periventricular white matter injury stands as a leading cause of cognitive, behavioral and motor impairment in preterm infants. There is epidemiological and histopathological evidence demonstrating the role of prenatal or neonatal inflammation in brain injury in preterm infants. In order to define the effect of an inflammatory insult in the developing brain on magnetic resonance (MR) imaging, we obtained high resolution conventional and diffusion MR images of the brain of rat pups after an inflammatory injury. Rat pups were subjected on postnatal day 5 (P5) to a stereotaxic injection of lipopolysaccharide in the corpus callosum and then imaged at 11.7 T on days 0, 2 and 4 following the injury. They were subsequently sacrificed for immunohistochemistry. Diffusion tensor imaging (DTI) acquired at high spatial resolution showed an initial reduction of the apparent diffusion coefficient (ADC) in the white matter. This was followed by an increase in ADC value and in T2 relaxation time constant in the white matter, with an associated increase of radial diffusivity of the corpus callosum, and a 10-fold increase in ventricular size. On histology, these MR changes corresponded to widespread astrogliosis, and decreased proportion of the section areas containing cresyl violet positive stain. The increase in radial diffusivity, typically attributed to myelin loss, occurred in this case despite the absence of myelin at this developmental stage.

Quantitative EEG in babies at risk for hypoxic ischemic encephalopathy after perinatal asphyxia.

OBJECTIVE: To evaluate an electroencephalography (EEG)-based index, the Cerebral Health Index in babies (CHI/b), for identification of neonates with high Sarnat scores and abnormal EEG as markers of hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. STUDY DESIGN: This is a retrospective study using 30 min of EEG data collected from 20 term neonates with HIE and 20 neurologically normal neonates. The HIE diagnosis was made on clinical grounds based on history and examination findings. The maximum-modified clinical Sarnat score was used to grade HIE severity within 72 h of life. All neonates underwent 2-channel bedside EEG monitoring. A trained electroencephalographer blinded to clinical data visually classified each EEG as normal, mild or severely abnormal. The CHI/b was trained using data from Channel 1 and tested on Channel 2. RESULT: The CHI/b distinguished among HIE and controls (P<0.02) and among the three visually interpreted EEG categories (P<0.0002). It showed a sensitivity of 82.4% and specificity of 100% in detecting high grades of neonatal encephalopathy (Sarnat 2 and 3), with an area under the receiver operator characteristic (ROC) curve of 0.912. CHI/b also identified differences between normal vs mildly abnormal (P<0.005), mild vs severely abnormal (P<0.01) and normal vs severe (P<0.002) EEG groups. An ROC curve analysis showed that the optimal ability of CHI/b to discriminate poor outcome was 89.7% (sensitivity: 87.5%; specificity: 82.4%). CONCLUSION: The CHI/b identified neonates with high Sarnat scores and abnormal EEG. These results support its potential as an objective indicator of neurological injury in infants with HIE.

Measuring preterm cumulative stressors within the NICU: the Neonatal Infant Stressor Scale.

BACKGROUND: Stress experiences, while pervasive, are less likely than painful experiences to be managed in still-hospitalised preterm infants. AIM: We aimed to quantify the severity of common stressors for preterm infants with a view to providing a tool to manage presumed accumulated infant stress. METHODS AND SUBJECTS: Seventeen doctors and 130 nurses who work in Neonatal Intensive and Special Care Nurseries rated the perceived stress severity of 44 acute events and 24 chronic living conditions for preterm infants at three ages (<28 weeks, 28-32 weeks, >32 weeks post-conceptional age) and for themselves. Acute items (such as heel lance) were organised into nursing, peripheral venous access, peripheral arterial access, central vascular access, ventilation, nutrition, medical procedures, surgery, radiology and miscellaneous categories. Chronic living conditions included items such as receiving intranasal oxygen and having a systemic infection. RESULTS: Doctors and nurses perceived nearly all items to be stressful to infants to some degree and to be equally stressful across ages. The degree of stress experienced by clinicians themselves was generally low and moderately correlated with presumed infant stress for the same items. Presumed infant stress was inversely related to clinician age. CONCLUSION: Based on these results we developed the Neonatal Infant Stressor Scale to help track, measure and manage presumed accumulated stress in preterm neonates.

Very preterm children show impairments across multiple neurodevelopmental domains by age 4 years.

OBJECTIVES: Neurodevelopmental outcomes associated with preterm birth are of major health and educational concern. This study examined the neuromotor, cognitive, language and emotional/behavioural outcomes of a regional cohort of 4-year-old children born extremely preterm (EPT: 23-27 weeks' gestation), very preterm (VPT: 28-33 weeks) and full term (FT: 38-41 weeks). Of particular interest were children's risks of impairment across multiple neurodevelopmental domains. METHODS: Data were gathered as part of a prospective longitudinal study of 105 very preterm (< or = 33 weeks gestation) and 107 FT children born during 1998-2000. At 4 years corrected age, children underwent a comprehensive multidisciplinary assessment that included a paediatric neurological examination, cognitive and language testing, and an assessment of child emotional and behavioural adjustment. RESULTS: At age 4 years, compared to FT children, EPT and VPT children had increased risks of cerebral palsy (EPT 18%, VPT 15%, FT 1%), cognitive delay (EPT 33%, VPT 36%, FT 13%), language delay (EPT 29%, VPT 29%, FT 10%) and emotional/behavioural adjustment problems (EPT 37%, VPT 13%, FT 11%). EPT and VPT children were three times more likely to have multiple domain impairments than FT children (EPT 30%, VPT 29%, FT 10%). CONCLUSIONS: A substantial proportion of preschool children born very preterm show clinically significant problems in at least one neurodevelopmental domain, with impairment in multiple domains being common. There is a need to monitor preschool development across a range of functional domains and to consider the likely cascading effects of multiple impairments on later development.

Abnormal white matter signal on MR imaging is related to abnormal tissue microstructure.

BACKGROUND AND PURPOSE: White matter signal-intensity abnormalities (WMSA) on MR imaging are related to adverse neurodevelopmental outcome in extremely preterm infants. Diffusion tensor imaging (DTI) may detect alterations in cerebral white matter microstructure and thus may help confirm the pathologic basis of WMSA. This study aimed to relate regional DTI measures with severity of WMSA in very preterm infants. MATERIALS AND METHODS: One hundred eleven preterm infants (birth weight, <1250 g and/or gestational age, <30 weeks) were scanned at term-equivalent age (1.5T). WMSA were classified as normal, focal, or extensive. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial (lambda1), and radial ([lambda2 + lambda3]/2) diffusivity were calculated in 12 regions of interest placed in the bilateral posterior limbs of the internal capsule, frontal (superior and inferior), sensorimotor, and occipital (superior and inferior) white matter regions. Data were compared by using 1-way analysis of variance, with a Bonferroni correction for multiple comparisons. RESULTS: Thirty-nine infants had normal, 59 infants had focal, and 13 infants had extensive WMSA. Compared with infants with normal or focal WMSA, infants with extensive WMSA had significantly lower FA in the internal capsule (P < .001), right inferior frontal regions (P < .05), and right superior occipital regions (P = .01); and higher radial diffusivity in the right internal capsule (P = .005), bilateral sensorimotor (P < .05), and right superior occipital regions (P < .05). Compared with infants with normal WMSA, infants with extensive WMSA had significantly higher ADC in bilateral sensorimotor regions (P < .01) and right superior occipital regions (P = .01), and lower axial diffusivity in the bilateral sensorimotor regions (P < .05). CONCLUSIONS: There are significant region-specific changes in ADC, FA, radial diffusivity, and axial diffusivity in preterm infants with extensive WMSA. Altered radial diffusivity was most prominent. This implies that disrupted premyelinating oligodendroglia is the major correlate with extensive WMSA rather than axonal pathology.