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.

Clinical correlates of cerebellar injury in preterm infants with surgical necrotizing enterocolitis.

BACKGROUND: The preterm infants are at risk of cerebellar injury and the risk factors for necrotizing enterocolitis (NEC) associated cerebellar injury are not fully understood. AIM: Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). METHODS: Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury detected on brain MRI obtained at term equivalent age. Cerebellar Injury patterns that we identified on MRI brain were cerebellar hemorrhage, siderosis and/or cerebellar volume loss. RESULTS: Cerebellar injury (21/65, 32.3%) in preterm infants with NEC was associated with patent ductus arteriosus (PDA) (18/21(85.7%) vs. 25/44(56.8%); p = 0.021), blood culture positive sepsis (13/21 (61.9%) vs. 11/44 (25%); p = 0.004) following NEC, predominantly grew gram positive bacteria (9/21(42.9%) vs. 4/44(9.1%); p = 0.001), greater red cell transfusion, higher rates of cholestasis following NEC and differences in intestinal histopathology (more hemorrhagic and reparative lesions) on univariate analysis. Those with cerebellar injury had higher grade white matter injury (14/21 (66.7%) vs. 4/44(9.1%) p = 0.0005) and higher-grade ROP (70.6% vs. 38.5%; p = 0.027) than those without cerebellar injury.On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe intestinal pathological hemorrhage (grade 3-4) (OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. CONCLUSION: Preterm infants with surgical NEC with positive blood culture sepsis, PDA, and severe intestinal hemorrhagic lesions (grade 3-4) appear at greater risk for cerebellar injury.

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.

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.

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.

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 relationship of selenium status to respiratory outcome in the very low birth weight infant.

OBJECTIVE: To examine the relationship between plasma and erythrocyte selenium and glutathione peroxidase (GPx) levels in premature infants and outcome measures. DESIGN: Prospective observational longitudinal study. SETTING: Two regional neonatal intensive care units in the South Island of New Zealand, an area with low soil selenium. PATIENTS: Seventy-nine infants with birth weights less than 1500 g or gestation less than 32 weeks admitted within 48 hours of birth from November 1992 through November 1993. MAIN OUTCOME MEASURES: Oxygen requirement at 28 days (chronic lung disease), or 36 weeks postmenstrual age and for all or most of the time from birth (bronchopulmonary dysplasia), total days in oxygen, retinopathy of prematurity, periventricular hemorrhage, or ventricular dilatation. RESULTS: Initial infant plasma selenium and GPx levels were about two thirds of maternal levels and fell a further 30% in 28 days. In contrast to adults, there was a poor correlation in infant plasma between selenium and GPx at birth and 28 days. Plasma selenium at 28 days was significantly lower in infants with chronic lung disease and bronchopulmonary dysplasia. After controlling for gestational age and age when fully fed orally, 28-day plasma selenium was significantly associated with the log of total days of oxygen requirement, each drop of 0.1 mumol/L in 28-day selenium being associated with a 58% increase in days of oxygen dependency. No significant associations of other parameters of selenium status and respiratory outcome were found, and there were no significant associations of any parameters of selenium status with other outcome measures. CONCLUSIONS: This study demonstrates for the first time in human infants that low plasma selenium levels are significantly associated with an increased respiratory morbidity. Whether selenium deficiency is etiologically important in determining the respiratory outcome or the result of sickness in the infant should be investigated in a randomized, controlled trial.

Endotracheal suctioning of the neonate: comparison of two methods as a source of mucus material for research.

Endotracheal suctioning in the neonatal intensive care setting is a routine procedure performed to maintain patency of the airway in ventilated infants. Harvested material can also be a source of mucus for research into neonatal respiratory disorders. We aimed to investigate whether the composition of material obtained by our clinically preferred technique of dry shallow suctioning differed significantly from that obtained with saline lavage and deep suctioning. Eleven pairs of dry and saline lavage aspiration samples were compared for neutrophil enzyme myeloperoxidase, total and active alpha(1)-antitrypsin, alpha(1)-antitrypsin complexed with elastase, and secretory leukoprotease inhibitor. Even though individual values of each analyte, expressed per gram of albumin, varied over at least a fivefold range, there was no difference between mean values of dry and lavage samples for any of the constituents. We conclude that the yield of material for research obtained by dry shallow suctioning is adequate and the quality at least as satisfactory as that provided by saline lavage.

Lipid peroxidation as a measure of oxygen free radical damage in the very low birthweight infant.

(ABSTRACTOxygen free radical mediated tissue injury is implicated as a major factor in the pathogenesis of the long term complications seen in the premature infant, and direct evidence of their role in the development of these long term problems is lacking. A prospective observational study of 78% of very low birthweight infants admitted to a level III neonatal intensive care unit in 1992 was undertaken to determine the relationship between lipid peroxidation products, antioxidant activity, and outcome. Lipid peroxidation (malondialdehyde-thiobarbituric acid, MDA-TBA) and antioxidant activity (vitamin E and glutathione peroxidase activity) were measured in 22 very low birthweight infants in the cord blood and the infant's blood at 24 hours, 48 hours, and 1 week of age and correlated with outcome measures. The normal range for these measures was established in the cord blood samples of 48 consecutive healthy full term infants. The concentration of MDA-TBA at 1 week correlated with the number of days of oxygen treatment and number of days of positive pressure ventilatory support. Controlling for gestational age and antenatal complications simultaneously the MDA-TBA concentration remained significantly associated with the number of days of oxygen treatment and the number of days of positive pressure ventilatory support. Glutathione peroxidase was low in the premature and full term infants consistent with the low concentrations of selenium known to be present in southern New Zealand. There was evidence of a quadratic relationship between vitamin E at 1 week and the total number of days of supplementary oxygen requirement, with both high and low values associated with increased oxygen requirement. This association, however, did not remain after controlling for gestational age and antenatal complications. These results support the role of oxygen free radicals in mediating tissue damage associated with the development of chronic lung disease in the premature infant.

Posthaemorrhagic ventricular dilatation in the premature infant: natural history and predictors of outcome.

OBJECTIVE: To investigate the natural history and predictors of outcome of posthaemorrhagic ventriculomegaly in the very low birthweight (VLBW) infant. METHODS: All VLBW infants admitted between September 1994 and September 1997 to the neonatal intensive care units of Brigham and Women's Hospital (Boston), Children's Hospital (Boston), and Christchurch Women's Hospital (New Zealand) with germinal matrix intraventricular haemorrhage (IVH) were identified. All charts and ultrasound scans were reviewed to define the natural history and perinatal and/or postnatal factors of value in prediction of the course of posthaemorrhagic ventriculomegaly. Progressive ventricular dilatation (PVD) was defined from the results of serial cranial ultrasound scans. RESULTS: A total of 248 VLBW infants had evidence of IVH (22% of all VLBW infants, mean (SD) gestational age 26.8 (2.6) weeks). A quarter of the infants exhibited PVD. Spontaneous arrest of PVD occurred without treatment in 38% of infants with PVD. Of the remaining 62% with persistent PVD, 48% received non-surgical treatment only (pharmacological and/or drainage of cerebrospinal fluid by serial lumbar punctures), 34% received surgical treatment with insertion of a ventriculoperitoneal reservoir and/or shunt, and 18% died. The development of PVD after IVH and adverse short term outcome, such as the requirement for surgery, were predicted most strongly by the severity of IVH. CONCLUSIONS: These data reflect the natural history of PVD in the 1990s and show that, despite a slight reduction in its overall incidence, there appears to be a more aggressive course, with appreciable mortality and morbidity in the extremely premature infant. The major predictor of adverse short term outcome, defined as death or need for surgical intervention, was the severity of IVH. These findings may be valuable for the management of very small premature infants.

Recovery of congenital isolated pharyngeal dysfunction: implications for early management.

The authors describe a case of severe congenital dysphagia caused by isolated pharyngeal dysfunction to highlight the clinical variability in the time to spontaneous recovery of this syndrome. The infant demonstrated recovery at 2 months of age, much earlier than previously reported examples. This case assists in the definition of this syndrome. This diagnosis should be considered in the evaluation of infants with congenital dysphagia.

Plasma vitamin A levels in the very low birthweight infant--relationship to respiratory outcome.

OBJECTIVE: To examine the association between plasma vitamin A levels and outcome measures in very low birthweight (VLBW) infants, including meta-analysis of all observational studies. DESIGN: A prospective observational longitudinal study of plasma vitamin A levels measured in the cord blood; maternal blood in the first 48 h after delivery; and the infants' blood at 48 h, 7 days and 28 days of age and correlated with antenatal and postnatal events. A meta-analysis of all published observational studies on the association of vitamin A with respiratory outcome in the VLBW infant was undertaken. PATIENTS: Fifty-seven infants (88% of all eligible) VLBW infants (< 1500 g) admitted from January through October 1993 to one of two regional neonatal intensive care units in the South Island of New Zealand. RESULTS: Exposure to antenatal steroids led to a significant increase in infant cord plasma vitamin A levels (P = 0.003), but no influence on infant plasma vitamin A levels at any other time. Exposure to postnatal steroids produced a significant rise in infant plasma vitamin A levels between 7 and 28 days (P = 0.008). After controlling for gestational age, antenatal and postnatal steroid exposure, low vitamin A levels at 48 h increased the risk of developing chronic lung disease (odds ratio for 50 microg/l decrease: 2.04, 95% CI 1.19-5.77) and bronchopulmonary dysplasia (odds ratio 1.96, 95% CI 1.14-6.87). On combining our results in meta-analysis with those of other published prospective observational studies, infants with chronic lung disease had lower plasma vitamin A levels at all times. CONCLUSIONS: Our results support an association between low plasma vitamin A levels and adverse outcome in the VLBW infant.

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.

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.

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.

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.

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.

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.

A novel quantitative simple brain metric using MR imaging for preterm infants.

BACKGROUND AND PURPOSE: The application of volumetric techniques to preterm infants has revealed brain volume reductions. Such quantitative data are not available in routine neonatal radiologic care. The objective of this study was to develop simple brain metrics to compare brain size in preterm and term infants and to correlate these metrics with brain volumes from volumetric MR imaging techniques. MATERIALS AND METHODS: MR images from 189 preterm infants <30 weeks' gestational age or <1250 g birthweight scanned at term-equivalent age and 36 term infants were studied. Fifteen tissue and fluid measures were systematically evaluated on 4 selected sections. The results were correlated with total brain, gray matter, white matter, and CSF volumes. RESULTS: The mean bifrontal, biparietal, and transverse cerebellar diameters were reduced (-11.6%, 95% confidence interval [CI], -13.8% to -9.3%; -12%, 95% CI, -14% to -9.8%; and -8.7%, 95% CI, -10.5% to -7% respectively) and the mean left ventricle diameter was increased (+22.3%, 95% CI, 2.9%-41.6%) in preterm infants (P < .01). Strong correlations were found between the bifrontal and biparietal measures with total brain tissue volume, whereas the size of the ventricles and the interhemispheric measure correlated with CSF volume. Intraobserver reliability was high (intraclass correlation coefficients [ICC], >0.7), where interobserver agreement was acceptable for tissue measures (ICC, >0.6) but lower for fluid measures (ICC, <0.4). CONCLUSIONS: Simple brain metrics at term-equivalent age showed smaller brain diameters and increased ventricle size in preterm infants compared with full-term infants. These measures represent a reliable and easily applicable method to quantify brain growth and assess brain atrophy in this at-risk population.