Early skin-to-skin contact and the risk of intraventricular haemorrhage and sepsis in preterm infants.

AIM: This study aimed to investigate the risks of intraventricular haemorrhage (IVH) or sepsis in extremely and very preterm infants exposed to early skin-to-skin contact (SSC). METHODS: Data from the Swedish Neonatal Quality Register from 2015 to 2021 were extracted to compare the proportions of infants exposed and not exposed to SSC on day 0 and/or 1 in life that developed IVH or sepsis. RESULTS: A total of 2514 infants, 1005 extremely preterm and 1509 very preterm, were included. This amounted to 69% of all extremely and very preterm infants born during the study period. The proportion of infants with IVH exposed and not exposed to early SSC was 11% and 27%, an adjusted odds ratio (aOR) of 0.67 (95%CI 0.52-0.86, p = 0.002). The proportion of infants with sepsis exposed and not exposed to early SSC was 16% and 30%, an aOR of 0.94 (95%CI 0.75-1.2, p = 0.60). For extremely preterm infants, the proportion with sepsis when exposed and not exposed to early SSC was 29% and 44%, an aOR of 0.65 (95%CI 0.46-0.92, p = 0.015). CONCLUSION: In the current setting, the risk of IVH or sepsis is not increased when an extremely or very preterm infant is exposed to early SSC.

Key outcomes in childbirth: Development of a perinatal core outcome set for management of labor and delivery at or near term.

INTRODUCTION: Consistency and relevance of perinatal outcome measures are necessary basics for obstetric research, audit, and clinical counseling. Still, there is an unwarranted variation in reported perinatal outcomes, which impairs research synthesis, validity, and implementation, as well as clinical benchmarking and longitudinal comparisons. The aim of this study was to develop a short-term perinatal (fetal and neonatal) Core Outcome Set to be used in research and quality assurance of management of labor and delivery at or near term. MATERIAL AND METHODS: The methods were guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. The project was prospectively registered on July 2, 2020 in the Core Outcome Measures in Effectiveness Trials (COMET) data base (reference number 1593). A list of potential outcomes was created based on a systematic review of studies evaluating interventions for peripartum management at or near term (≥34 weeks of gestation), including decisions regarding timing and type of onset of labor, intrapartum care, and mode of delivery. The list was entered into a two-round Delphi survey with predefined consensus criteria. Participants (n = 67) included clinicians, researchers, lay persons with experience of childbirth (patient representatives), and other stakeholders. A consensus meeting was held to reach a final agreement. RESULTS: Response rates were 82.1% (55/67) and 92.7% (51/55) for the first and second Delphi rounds, respectively. In total, 17 outcomes were included in the final core outcome set, reflecting mortality, health or morbidity, including asphyxia, central nervous system status, infection, neonatal resuscitation and admission, breastfeeding and mother-infant interaction, operative delivery due to fetal distress, as well as birthweight and gestational age. Two of these outcomes were suggested by patient representatives. CONCLUSIONS: The Swedish Perinatal Core Outcome Set (SPeCOS) study involved a broad circle of relevant stakeholders and reached consensus on a minimal set of perinatal outcomes that should be collected and reported in a standardized way in all future studies on management of labor and delivery at or near term, regardless of the specific population or condition studied. This could improve obstetric research, evidence synthesis, uptake, implementation, and adherence, as well as clinical practice, audit, and comparisons in childbirth care.

Term-born infants with a perinatal stroke frequently had seizures and were prescribed anti-seizure medication at discharge.

AIM: We investigated the prevalence of seizures in term-born infants with a perinatal stroke in Swedish neonatal wards, assessed the anti-seizure medication prescribed and determined the accuracy of diagnostic codes. METHODS: This cross-sectional study used data from the Swedish Neonatal Quality Register. The cases were infants born at ≥37 weeks in 2009-2018 and admitted to a neonatal ward in Stockholm County with a stroke diagnosis, confirmed by their medical chart. The controls were all Swedish infants born during those years. RESULTS: There were 76 infants with a confirmed perinatal stroke: 51 ischaemic and 25 haemorrhagic. Seizures were documented in 66/76 (87%) of infants with a stroke and 0.2% of the controls. Anti-seizure medication was administered to 64/66 (97%) infants with a stroke and seizures. In 60 cases, the drugs administered were specified, with phenobarbital used in 59/60 cases (98%). More than one drug was administered to 25/60 (42%) infants and 31/60 (52%) were discharged with anti-seizure medication. The positive predictive value for the stroke diagnostic codes was 80.5% (95% CI 76.5-84.5). CONCLUSION: Seizures were common in infants with a perinatal stroke. More than one anti-seizure drug was often required and many infants were on anti-seizure medication at discharge, against Swedish recommendations.

Low Apgar score and need for resuscitation increased the probability of receiving therapeutic hypothermia more strongly than acidosis at birth.

AIM: The aim of this study was to investigate how individual markers for birth asphyxia, so-called A criteria, were associated with the probability of receiving therapeutic hypothermia. METHODS: This population-based cohort study included 1336 live-born singleton term infants with any A criterion in the Stockholm-Gotland Region, Sweden during 2008 to 2014. The Swedish Neonatal Quality Register and National Patient Register were used for data collection. Results were presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: There were 89 infants, 44 boys and 45 girls with mean gestational age 40.5 weeks, who received therapeutic hypothermia. Low Apgar score, aOR 12.44 (95% CI 5.99-25.86), and resuscitation, aOR 9.18 (95% CI 3.77-22.34), were strongly associated with therapeutic hypothermia. A pH <7.0 was less associated with the outcome, aOR 2.02 (95% CI 1.02-4.0). No infant who received therapeutic hypothermia fulfilled the criteria of base deficit ≥16 mmol/L only. CONCLUSION: A low Apgar score of and/or a need for resuscitation is more relevant for identifying infants eligible for therapeutic hypothermia, compared to other A criteria. This knowledge could be used clinically to identify cases for review and avoid unnecessary monitoring of infants.

Initiation and duration of skin-to-skin contact for extremely and very preterm infants: A register study.

AIM: This study sought to describe how skin-to-skin contact between extremely and very preterm infants and their parents is practised in Swedish neonatal units. METHODS: Data from the Swedish Neonatal Quality Register from 2020 to 2021 were extracted to analyse initiation time and daily duration of skin-to-skin contact in different gestational ages and regions. RESULTS: Of the 1475 infants in the cohort, mean (range) gestational age was 28 weeks (22-31), and mean (range) birthweight was 1205 g (360-2810). For extremely preterm infants (<28 weeks), median (interquartile range) skin-to-skin contact initiation time was at 88 postnatal hours (48-156) and 5% had skin-to-skin contact on the first day. For very preterm infants (<32 weeks), the corresponding numbers were 14 h (4-36) and 34%. Median (interquartile range) daily skin-to-skin contact duration for the entire cohort during the first day, first three and seven days and the remaining hospital stay was 0 (0-0), 0.7 (0-2.7), 1.6 (0.4-3.6) and 4.4 (3.0-6.1) h, respectively. CONCLUSION: A minority of extremely and very preterm infants were exposed to skin-to-skin contact on the first postnatal day. Daily duration during the first week of life amounted to less than two hours. Initiation time and daily duration varied among gestational ages.

The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years.

AIM: This study investigated patent ductus arteriosus (PDA) treatment and neurodevelopmental outcomes when extremely preterm born children reached 6.5 years. METHOD: Our cohort was 435 children with neonatal PDA treatment data and neurodevelopmental follow-up data, born in 2004-2007, who participated in the Extremely Preterm Infants in Sweden Study. Pharmacological or surgical PDA treatment and the age at PDA treatment, were investigated in relation to the risks of moderate to severe neurodevelopmental impairment (NDI) and full-scale intelligence quotient (FSIQ) at 6.5 years. RESULTS: The children who received PDA drug treatment, including those who also had surgery, had the same risk of moderate to severe NDI or lower FSIQ as untreated children. However, children who had primary PDA surgery faced increased risks of NDI, with an adjusted incidence rate ratio of 1.62 (95% confidence interval [CI] 1.28-2.06) and a lower adjusted mean difference FSIQ of -7.1 (95% CI -11 to -3.2). Surgery at less than 10 days of life was associated with a significantly increased risk of moderate to severe NDI and lower FSIQ than surgery after 20 days. CONCLUSION: Drug treatment followed by deferred surgery appeared to be a safer option for extremely preterm infants severely affected by PDA.

Immediate skin-to-skin contact is feasible for very preterm infants but thermal control remains a challenge.

AIM: Current care of very preterm infants in an incubator implies separation of the mother-infant dyad. The aim of this study was to determine whether skin-to-skin contact (SSC) between parent and very preterm infant from birth and during the first postnatal hour is feasible. METHODS: Infants born in 2014-16 in Stockholm at gestational age 28 + 0-33 + 6 weeks were randomised to care provided in SSC with a parent or on a resuscitaire and later in an incubator or bed during the first postnatal hour. Infant body temperature was measured on admission to the neonatal unit and at one postnatal hour. Data on respiratory support and breastfeeding were prospectively collected. RESULTS: We studied 55 infants at 32 + 0 ± 1.4 weeks (range 28 + 2-33 + 6), with birthweight 1760 g ± 449 g (range 885-2822). 60% were boys. Mean body temperature in the SSC group was 0.3°C lower 1 hour after birth, 36.3°C ± 0.52 (range 34.4-37.2) vs 36.6°C ± 0.42 (range 36.0-37.4, P = .03). No differences between groups were seen in respiratory support or breastfeeding. CONCLUSION: Stabilisation of very preterm infants can be performed while in SSC with a parent, but caution needs to be paid to maintain normothermia.

Moderate neonatal hypoglycemia and adverse neurological development at 2-6 years of age.

To determine whether moderate neonatal hypoglycemia in otherwise healthy infants is associated with adverse neurodevelopmental outcome in pre-school children. Population-based cohort study with prospectively collected register data from Sweden. All singletons born July 1st 2008 through December 31st 2012 (n = 101,060) in the region were included. Infants with congenital malformations, infants treated in neonatal intensive care unit, infants with inborn errors of metabolism and infants to mothers with diabetes were excluded. Infants were followed-up until 2014, at 2-6 years of age. Exposure was neonatal moderate hypoglycemia. Main outcomes were a compiled neurological or neurodevelopmental outcome; any developmental delay; motor developmental delay; and cognitive developmental delay. In adjusted regression analyses, the odds ratio (OR) of any neurological or neurodevelopmental outcome was 1.48 (95% confidence interval: 1.17-1.88) in hypoglycemic compared to normoglycemic infants. The adjusted risk of any developmental delay was more than doubled (OR 2.53 [1.71-3.73]), the adjusted risk of motor developmental delay was almost doubled (OR: 1.91 [1.06-3.44]) and the adjusted risk of cognitive developmental delay was almost tripled (OR 2.85 [1.70-4.76]). Infants with early neonatal hypoglycemia (< 6 h) had a double risk (OR 1.94 [1.30-2.89]) of any neurological or neurodevelopmental outcome and a tripled risk of cognitive developmental delay (OR 3.17 [1.35-7.43]), compared to normoglycemic infants. In the first population-based study on this topic, we show that moderate neonatal hypoglycemia is associated with increased risks of impaired neurodevelopment. Current treatment routines for uncomplicated hypoglycemia should be followed.

Predictors of unfavorable thermal outcome during newborn emergency retrievals.

OBJECTIVE: Maintenance of normal body temperature is a challenge during transports. We aimed to identify predisposing factors for unfavorable thermal outcome during emergency retrievals of neonates. METHODS: Demographic data and clinical variables for transports performed over a 2-year period were extracted from the Newborn Emergency Transport Service (Victoria, Australia) database. Arrival temperatures outside normothermia (36.5°-37.5°C) were defined as an unfavorable outcome. RESULTS: Normothermia on arrival at the receiving hospital was achieved in 78% of 1,261 transports. The strongest predictor of unfavorable thermal outcome was an abnormal temperature at the start of the retrieval (odds ratio [OR] = 8.04; 95% confidence interval [CI], 5.91-10.95; P < .001) followed by very low weight on transport (< 1,500 g; OR = 2.49; 95% CI, 1.63-3.80; P < .001) and respiratory support (OR = 1.81; 95% CI, 1.29-2.54; P = .001). Medications (eg, inotropes and sedation/muscle relaxation) or central/peripheral venous/arterial lines were not significant predictors of outcome when temperature at retrieval start, weight at transport, and respiratory support were adjusted as cofactors. Mode of transport (road, fixed wing, or rotary wing aircraft) and outside temperature were not associated with thermal outcome. CONCLUSION: Abnormal temperature at the start of the retrieval, very low transport weight, and respiratory support were strong predictors of unfavorable thermal outcome during neonatal emergency transports.

Sex differences in outcome and associations with neonatal brain morphology in extremely preterm children.

OBJECTIVE: To investigate sex differences in neurologic and developmental outcomes in extremely preterm (EPT) children and explore associations with neonatal brain morphology. STUDY DESIGN: A population-based cohort of infants born at <27 weeks gestation underwent magnetic resonance imaging (MRI) at term equivalent age (n = 107). Voxel-based morphometry (n = 27) and tract-based spatial statistics (n = 29) were performed in infants with normal MRI findings. Neurologic and developmental assessment (using the Bayley Scales of Infant and Toddler Development-Third Edition [BSITD-III]) was performed at 30 months corrected age (n = 91). RESULTS: EPT boys had lower mean cognitive composite scores (P = .03) and lower mean language composite scores (P = .04) compared with EPT girls. Rates of cerebral palsy were similar in the 2 sexes. No perinatal factor explained the variance in outcomes. Visual inspection of T1- and T2-weighted MRI images found that delayed myelination was found more frequently in boys, whereas cerebellar abnormalities were more common in girls. In the subgroup of children with normal MRI findings (n = 27), boys had poorer cognitive function (P = .015) and language function (P = .008), despite larger volumes of cerebellar tissue (P = .029). In boys, cerebellar volume was positively correlated with BSITD-III cognitive and motor scores (P = .04 for both). In girls, white matter volume (P = .02) and cortical gray matter volume (P = .03) were positively correlated with BSITD-III language score. At the regional level, significant correlations with outcomes were found only in girls. CONCLUSION: Cognitive and language outcomes at age 30 months were poorer in boys. Sex-related differences were observed on neonatal structural MRI, including differences in the patterns of correlations between brain volumes and developmental scores at both global and regional levels.

White matter microstructure is influenced by extremely preterm birth and neonatal respiratory factors.

AIM: The aim of this study was to investigate whether prematurity per se or perinatal risk factors explain altered brain structure after preterm birth, in extremely preterm (EPT) infants without focal brain lesions. METHODS: A population-based cohort of 58 EPT infants [gestational age (GA) <27 + 0 weeks] was examined with diffusion magnetic resonance imaging at term-equivalent age and compared with 14 term-born controls. Associations of diffusion measures with prematurity and neonatal risk factors were explored. Data were analysed with tract-based spatial statistics (TBSS) for whole-brain analysis and region-of-interest (ROI) analysis. RESULTS: Whole-brain analyses showed lower fractional anisotropy (FA) and higher mean diffusivity (MD) in several white matter (WM) tracts in the preterms, which was essentially confirmed by ROI analyses. Within the preterm GA range (23 + 0 to 26 + 6 weeks), GA at birth was not significantly associated with diffusion measures. Bronchopulmonary dysplasia predicted lower FA in the corpus callosum and right inferior longitudinal fasciculus; mechanical ventilation >2 days was predictive of higher MD in the right external capsule. CONCLUSION: White matter microstructure is influenced by preterm birth and by neonatal respiratory factors, whereas the degree of prematurity within the EPT range appears to be of less importance.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants.

OBJECTIVE: To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN: This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS: Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION: This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

White matter changes in extremely preterm infants, a population-based diffusion tensor imaging study.

AIM: To investigate cerebral white matter (WM) abnormalities (J Pediatr 2003; 143: 171) and diffuse and excessive high signal intensities (DEHSI), (J Pediatr 1999; 135: 351) in a cohort of extremely preterm infants born in Stockholm during a 3-year period, using magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: MRI at term-equivalent age was performed in 109 infants and DTI data were acquired in 54 infants. Survival rate in the entire cohort was 67%. Sixteen term-born healthy control infants were scanned for comparison. RESULTS: No or mild WM abnormalities were seen in 86% of infants and 14% had moderate or severe WM abnormalities. DEHSI were seen in infants with all grades of white matter abnormalities and were present in 56% of infants. In the WM at the level of centrum semiovale, infants with any WM abnormalities or DEHSI had lower Fractional Anisotropy and higher Apparent Diffusion Coefficient compared with control infants. No significant differences in diffusion were seen in infants without DEHSI compared with the controls in this region. Compared with controls, the preterm infants had significantly altered diffusion in the corpus callosum. CONCLUSION: Only 14% of the extremely preterm infants had moderate or severe WM abnormalities on MRI. However, the incidence of DEHSI was high. In the DEHSI regions, changes in diffusion parameters were detected, indicating altered WM organization.

Spontaneous brain activity in the newborn brain during natural sleep--an fMRI study in infants born at full term.

Recent progress in functional neuroimaging research has provided the opportunity to probe at the brain's intrinsic functional architecture. Synchronized spontaneous neuronal activity is present in the form of resting-state networks in the brain even in the absence of external stimuli. The objective of this study was to investigate the presence of resting-state networks in the unsedated infant brain born at full term. Using functional MRI, we investigated spontaneous low-frequency signal fluctuations in 19 healthy full-term infants. Resting-state functional MRI data acquired during natural sleep was analyzed using independent component analysis. We found five resting-state networks in the unsedated infant brain born at full term, encompassing sensory cortices, parietal and temporal areas, and the prefrontal cortex. In addition, we found evidence for a resting-state network that enclosed the bilateral basal ganglia.

A Novel Scoring System for Term-Equivalent-Age Cranial Ultrasound in Extremely Preterm Infants.

The role of term-equivalent-age (TEA) cranial ultrasound (cUS) in predicting outcome in preterm infants is increasingly being recognized. However, a detailed quantitative scoring system that allows comparison of groups and comparison with TEA magnetic resonance imaging (MRI) scoring systems is lacking. Eighty-four extremely preterm infants underwent cUS and MRI at TEA. Cranial US was evaluated using a novel detailed scoring system. Agreement between cUS and MRI scores was good (Spearman's ρ = 0.51, p < 0.001). Outcome at 30 mo corrected was assessed in 66 of 84 preterm and 85 term-born infants. Sensitivity was the same for cUS and MRI in prediction of cerebral palsy (75%) and severe cognitive delay (100%); the specificity was slightly higher for MRI (cerebral palsy: 97% vs. 90%, severe cognitive delay: 95% vs. 90%). The proposed novel cUS scoring system is a helpful tool in quantitative assessment of cUS at TEA and prediction of outcome at 30 mo.

Effects of Intrauterine Inflammation on Cortical Gray Matter of Near-Term Lambs.

Introduction: Ventilation causes cerebral white matter inflammation and injury, which is exacerbated by intrauterine inflammation. However, the effects on cortical gray matter are not well-known. Our aim was to examine the effect of ventilation on the cerebral cortex of near-term lambs exposed to intrauterine inflammation. Method:Pregnant ewes at 119 ± 1 days gestation received an intra-amniotic injection of saline or lipopolysaccharide (LPS; 10 mg). Seven days later, lambs were randomized to either a high tidal volume injurious ventilation strategy (INJSALN = 6, INJLPSN = 5) or a protective ventilation strategy (PROTSALN = 5, PROTLPSN = 6). Respiratory parameters, heart rate and blood gases were monitored during the neonatal period. At post-mortem, the brain was collected and processed for immunohistochemical assessment. Neuronal density (NeuN), apoptotic cell death (caspase 8 and TUNEL), microglial density (Iba-1), astrocytic density (GFAP), and vascular protein extravasation (sheep serum) were assessed within the frontal, parietal, temporal and occipital lobes of the cerebral cortex. Results:A significant reduction in the number of neurons in all cortical layers except 4 was observed in LPS-exposed lambs compared to controls (layer #1: p = 0.041; layers #2 + 3: p = 0.023; layers #5 + 6: p = 0.016). LPS treatment caused a significant increase in gray matter area, indicative of edema. LPS+ventilation did not cause apoptotic cell death in the gray matter. Astrogliosis was not observed following PROT or INJ ventilation, with or without LPS exposure. LPS exposure was associated with vascular protein extravasation. Conclusion:Ventilation had little effect on gray matter inflammation and injury. Intrauterine inflammation reduced neuronal cell density, caused edema of the cortical gray matter, and blood vessel extravasation in the brain of near-term lambs.

Diffusion Tensor Imaging Colour Mapping Threshold for Identification of Ventilation-Induced Brain Injury after Intrauterine Inflammation in Preterm Lambs.

PURPOSE: The aim of this study is to examine whether advanced magnetic resonance imaging (MRI) techniques can detect early brain injury caused by intrauterine inflammation and inappropriate initial respiratory support in preterm lambs. HYPOTHESIS: Neuropathology caused by intrauterine inflammation is exacerbated by mechanical ventilation at birth and is detectable with advanced MRI techniques. METHODS: Pregnant ewes received intra-amniotic lipopolysaccharide (LPS) 7 days prior to delivery at ~125 days of gestation (85% of gestation), whereupon lambs were delivered and randomised to receive an injurious (LPS + INJ, n = 6) or protective (LPS + PROT, n = 6) ventilation strategy. MRI of the brain was conducted 90 min after preterm delivery, using structural, diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) techniques. A colour map threshold technique was utilised to compare distributions of low diffusivity voxels in the brains of LPS-exposed lambs with those not exposed to LPS (PROT, n = 7 PROT and INJ, n = 10). RESULTS: No overt cerebral injury was identified on structural MRI images of any lamb. However, on DTI, axial diffusivity, radial diffusivity, and mean diffusivity values were lower and significantly more heterogeneous in specific brain regions of lambs in the LPS + INJ group compared to the LPS + PROT group. Colour mapping revealed lower diffusivity in the thalamus, periventricular white matter, internal capsule, and frontal white matter in the LPS + INJ group compared to LPS + PROT group. The MRS peak area ratios of lactate, relative to those for the metabolites creatine, choline, and N-acetylaspartate, were not different between LPS-exposed groups. Lambs exposed to LPS had lower diffusivity within the white matter regions assessed than non-LPS-treated control lambs. CONCLUSION: DTI colour map threshold techniques detected early brain injury in preterm lambs exposed to intrauterine inflammation and detected differences between injurious and protective ventilation strategies. DTI mapping approaches are potentially useful for early detection of subtle brain injury in premature infants.

Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm.

OBJECTIVE: Magnetic resonance imaging (MRI) of the brain carried out during the neonatal period shows that 55-80% of extremely preterm infants display white matter diffuse excessive high signal intensity (DEHSI). Our aim was to study differences in developmental outcome at the age of 6.5 years in children born extremely preterm with and without DEHSI. STUDY DESIGN: This was a prospective cohort study of 83 children who were born in Stockholm, Sweden, between 2004 and 2007, born at gestational age of < 27 weeks + 0 days and who underwent an MRI scan of their brain at term equivalent age. The outcome measures at 6.5 years included testing 66 children with the modified Touwen neurology examination, the Movement Assessment Battery for Children 2, the Wechsler Intelligence Scale for Children-Fourth Edition, Beery Visual-motor Integration test-Sixth Edition, and the Strengths and Difficulties Questionnaire. Group-wise comparisons were done between children with and without DEHSI using Student t-test, Mann Whitney U test, Chi square test and regression analysis. RESULTS: DEHSI was detected in 39 (59%) of the 66 children who were assessed at 6.5 years. The presence of DEHSI was not associated with mild neurological dysfunction, scores on M-ABC assessment, cognition, visual-motor integration, or behavior at 6.5 years. CONCLUSION: The presence of qualitatively defined DEHSI on neonatal MRI did not prove to be a useful predictor of long-term impairment in children born extremely preterm.

Early detection of ventilation-induced brain injury using magnetic resonance spectroscopy and diffusion tensor imaging: an in vivo study in preterm lambs.

BACKGROUND AND AIM: High tidal volume (VT) ventilation during resuscitation of preterm lambs results in brain injury evident histologically within hours after birth. We aimed to investigate whether magnetic resonance spectroscopy (MRS) and/or diffusion tensor imaging (DTI) can be used for early in vivo detection of ventilation-induced brain injury in preterm lambs. METHODS: Newborn lambs (0.85 gestation) were stabilized with a "protective ventilation" strategy (PROT, n = 7: prophylactic Curosurf, sustained inflation, VT 7 mL/kg, positive end expiratory pressure (PEEP) 5 cmH2O) or an initial 15 minutes of "injurious ventilation" (INJ, n = 10: VT 12 mL/kg, no PEEP, late Curosurf) followed by PROT ventilation for the remainder of the experiment. At 1 hour, lambs underwent structural magnetic resonance imaging (Siemens, 3 Tesla). For measures of mean/axial/radial diffusivity (MD, AD, RD) and fractional anisotropy (FA), 30 direction DTI was performed. Regions of interests encompassed the thalamus, internal capsule, periventricular white matter and the cerebellar vermis. MRS was performed using a localized single-voxel (15×15×20 mm3, echo time 270 ms) encompassing suptratentorial deep nuclear grey matter and central white matter. Peak-area ratios for lactate (Lac) relative to N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were calculated. Groups were compared using 2-way RM-ANOVA, Mann-Whitney U-test and Spearman's correlations. RESULTS: No cerebral injury was seen on structural MR images. Lambs in the INJ group had higher mean FA and lower mean RD in the thalamus compared to PROT lambs, but not in the other regions of interest. Peak-area lactate ratios >1.0 was only seen in INJ lambs. A trend of higher mean peak-area ratios for Lac/Cr and Lac/Cho was seen, which correlated with lower pH in both groups. CONCLUSION: Acute changes in brain diffusion measures and metabolite peak-area ratios were observed after injurious ventilation. Early MRS/DTI is able to detect the initiation of ventilation-induced brain injury.

General movements and magnetic resonance imaging in the prediction of neuromotor outcome in children born extremely preterm.

BACKGROUND: Extremely preterm (EPT) birth is a major risk factor for brain injury and neurodevelopmental impairment. Reliable tools for early prediction of outcome are warranted. AIM: To investigate the predictive value of general movements (GMs) at "fidgety age" for neurological outcome at age 30 months in EPT infants, both in comparison and in combination with structural magnetic resonance imaging (MRI) at term equivalent age (TEA). STUDY DESIGN: Fifty-three infants born <27 weeks of gestation were included prospectively. MRI was performed at TEA and images were evaluated for white and grey matter abnormalities. GMs were assessed at age 3 months corrected ("fidgety age"). OUTCOME MEASURES: Neuromotor outcome was assessed at age 30months corrected. Children were classified as having a normal neurological status, unspecific signs, or cerebral palsy (CP). RESULTS: Abnormal GMs were a common finding, seen in 32% (17/53) of infants. Of these, six infants (11%) had definitely abnormal GMs. Four infants (8%) had a diagnosis of CP at follow up. Definitely abnormal GMs were significantly associated to CP at 30 months (Fisher's Exact test p=0.03, sensitivity 50%, specificity 92%). Moderate-severe white matter abnormalities on MRI were more strongly associated with CP (Fisher's Exact test p<0.001, sensitivity 100%, specificity 98%) than GMs. Combining GMs with MRI-findings at TEA increased the predictive specificity to 100% (Fisher's Exact test, p=0.005), whereas sensitivity remained unchanged. CONCLUSIONS: The presence of definitely abnormal GMs was predictive of CP: prediction was significantly enhanced when the GMs assessment was combined with findings from MRI obtained at TEA.