Children had smaller brain volumes and cortical surface areas after prenatal opioid maintenance therapy exposure.

AIM: The studies have shown that infants with prenatal OMT exposure had smaller brain volumes than non-exposed controls, but long-term outcome data are lacking. We examined 5-13-year-old OMT-exposed children with brain MRI and tested motor and visual-motor functions and possible associations between brain morphology and outcome. METHODS: To this retrospective cohort study, we recruited 55 children with prenatal OMT exposure and 59 age- and gender-matched controls. They were examined with brain MRI, Movement-ABC and Beery-VMI. MRI images were processed with the Free Surfer® software to obtain volumetrics and estimates of cortical surface area and thickness. We used a general linear regression model (GLM) to calculate group differences. RESULTS: The children in the OMT group had smaller mean total intracranial volume (ICV), 1407 cm3 (CI 95% 1379-1434) versus 1450 cm3 (CI 95% 1423-1476) in the control group (p = 0.026). After adjusting for ICV, significant group differences persisted for volumes of amygdala, basal ganglia and mid-posterior part of corpus callosum. Cortical surface area was smaller in the left caudal middle frontal gyrus and the right inferior parietal lobule in the OMT-group. Visual-motor function was significantly correlated with ICV. CONCLUSION: Prenatal OMT exposure may alter early brain development with possible negative long-term functional consequences.

Estimated cumulative radiation dose received by diagnostic imaging during staging and treatment of operable Ewing sarcoma 2005-2012.

BACKGROUND: Patients with Ewing sarcoma are subject to various diagnostic procedures that incur exposure to ionising radiation. OBJECTIVE: To estimate the radiation doses received from all radiologic and nuclear imaging episodes during diagnosis and treatment, and to determine whether 18F-fluorodeoxyglucose positron emission tomography - computed tomography (18F-FDG PET-CT) is a major contributor of radiation. MATERIALS AND METHODS: Twenty Ewing sarcoma patients diagnosed in Norway in 2005-2012 met the inclusion criteria (age <30 years, operable disease, uncomplicated chemotherapy and surgery, no metastasis or residual disease within a year of diagnosis). Radiation doses from all imaging during the first year were calculated for each patient. RESULTS: The mean estimated cumulative radiation dose for all patients was 34 mSv (range: 6-70), radiography accounting for 3 mSv (range: 0.2-12), CT for 13 mSv (range: 2-28) and nuclear medicine for 18 mSv (range: 2-47). For the patients examined with PET-CT, the mean estimated cumulative effective dose was 38 mSv, of which PET-CT accounted for 14 mSv (37%). CONCLUSION: There was large variation in number and type of examinations performed and also in estimated cumulative radiation dose. The mean radiation dose for patients examined with PET-CT was 23% higher than for patients not examined with PET-CT.

Selective ultrasound screening for developmental hip dysplasia: effect on management and late detected cases. A prospective survey during 1991-2006.

BACKGROUND: Early treatment is considered essential for developmental dysplasia of the hip (DDH), but the choice of screening strategy is debated. OBJECTIVE: We evaluated the effect of a selective ultrasound (US) screening programme. MATERIALS AND METHODS: All infants born in a defined region during 1991-2006 with increased risk of developmental dysplasia of the hip, i.e. clinical hip instability, breech presentation, congenital foot deformities or a family history of DDH, underwent US screening at age 1-3 days. Severe sonographic dysplasia and dislocatable/dislocated hips were treated with abduction splints. Mild dysplasia and pathological instability, i.e. not dislocatable/dislocated hips were followed clinically and sonographically until spontaneous resolution, or until treatment became necessary. The minimum observation period was 5.5 years. RESULTS: Of 81,564 newborns, 11,539 (14.1%) were identified as at-risk, of whom 11,190 (58% girls) were included for further analyses. Of the 81,564 infants, 2,433 (3.0%) received early treatment; 1,882 (2.3%) from birth and 551 (0.7%) after 6 weeks or more of clinical and sonographic surveillance. An additional 2,700 (3.3%) normalised spontaneously after watchful waiting from birth. Twenty-six infants (0.32 per 1,000, 92% girls, two from the risk group) presented with late subluxated/dislocated hips (after 1 month of age). An additional 126 (1.5 per 1,000, 83% girls, one from the risk group) were treated after isolated late residual dysplasia. Thirty-one children (0.38 per 1,000) had surgical treatment before age 5 years. Avascular necrosis was diagnosed in seven of all children treated (0.27%), four after early and three after late treatment. CONCLUSION: The first 16 years of a standardised selective US screening programme for developmental dysplasia of the hip resulted in acceptable rates of early treatment and US follow-ups and low rates of late subluxated/dislocated hips compared to similar studies.

Association between brain activation (fMRI), cognition and school performance in extremely preterm and term born children.

The purpose of the study was to investigate a possible association between brain activation in functional magnetic resonance imaging scans, cognition and school performance in extremely preterm children and term born controls. Twenty eight preterm and 28 term born children were scanned while performing a working memory/selective attention task, and school results from national standardized tests were collected. Brain activation maps reflected difference in cognitive skills but not in school performance. Differences in brain activation were found between children born preterm and at term, and between high and low performers in cognitive tests. However, the differences were located in different brain areas. The implication may be that lack of cognitive skills does not alone explain low performance due to prematurity.

Histologic chorioamnionitis in extremely preterm births, microbiological findings and infant outcome.

BACKGROUND: Histologic chorioamnionitis (HCA) is most often caused by ascending bacterial infection originating from the cervicovaginal tract. OBJECTIVES: To investigate whether HCA with a fetal inflammatory response (FIR) has a worse clinical outcome than HCA alone. Further, if FIR or a positive maternal microbiologic culture obtained prior to birth were related to adverse neonatal outcomes in a cohort of extremely preterm (EP) neonates. METHODS: Prospective observational cohort study recruiting EP singleton pregnancies (gestational age at birth ≤28 weeks) with confirmed HCA. FIR was defined by fetal neutrophils in the chorionic vessels and/or umbilical vessels. Positive culture was defined as growth of potentially pathogenic bacteria in a sample from the cervicovaginal tract prior to birth, or if a cervicovaginal culture was lacking, a culture result from the placenta was used. Logistic regression was used to estimate odds ratios and 95% confidence intervals for the associations between FIR, a positive culture result and adverse outcomes, defined as bronchopulmonary dysplasia (BPD), brain pathology assessed by magnetic resonance imaging, retinopathy of prematurity, necrotizing enterocolitis, early-onset neonatal sepsis, and perinatal death. A composite outcome variable included one or more adverse outcomes. RESULTS: We included 71 cases with HCA, of which 51 (72%) had FIR. Maternal age, rate of clinical chorioamnionitis (CCA), preterm pre-labor rupture of membranes (PPROM), the number of women receiving antenatal steroids and antibiotics, and the rate of positive maternal cultures of potentially pathogenic bacteria were all significantly higher in the HCA with FIR. Neonates in the FIR group had significantly higher levels of blood leukocytes compared to those without. FIR was associated with a longer interval from PPROM to delivery (log-rank test: p = .022). Microbiological sampling had been performed in 63 (89%) cases, of which 60 (95%) were cervicovaginal samples. No associations were found between a positive culture and adverse neonatal outcomes, in contrast to FIR, that was significantly associated to BPD and brain pathology. CONCLUSIONS: In a cohort of EP pregnancies with confirmed HCA, the presence of FIR was associated with advanced maternal age, CCA, PPROM, antenatal steroids and antibiotics, and a positive maternal culture of potentially pathogenic bacteria. However, the presence of FIR, and not a positive culture, was associated with adverse neonatal outcomes.

Acute kidney injury in patients with COVID-19 in the intensive care unit: evaluation of risk factors and mortality in a national cohort.

OBJECTIVES: Acute kidney injury (AKI) is a frequent complication among critical ill patients with COVID-19, but the actual incidence is unknown as AKI-incidence varies from 25% to 89% in intensive care unit (ICU) populations. We aimed to describe the prevalence and risk factors of AKI in patients with COVID-19 admitted to ICU in Norway. DESIGN: Nation-wide observational study with data sampled from the Norwegian Intensive Care and Pandemic Registry (NIPaR) for the period between 10 March until 31 December 2020. SETTING: ICU patients with COVID-19 in Norway. NIPaR collects data on intensive care stays covering more than 90% of Norwegian ICU and 98% of ICU stays. PARTICIPANTS: Adult patients with COVID-19 admitted to Norwegian ICU were included in the study. Patients with chronic kidney disease (CKD) were excluded in order to avoid bias from CKD on the incidence of AKI. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was AKI at ICU admission as defined by renal Simplified Acute Physiology Score in NIPaR. Secondary outcome measures included survival at 30 and 90 days after admission to hospital. RESULTS: A total number of 361 patients with COVID-19 were included in the analysis. AKI was present in 32.0% of the patients at ICU admission. The risk for AKI at ICU admission was related to acute circulatory failure at admission to hospital. Survival for the study population at 30 and 90 days was 82.5% and 77.6%, respectively. Cancer was a predictor of 30-day mortality. Age, acute circulatory failure at hospital admission and AKI at ICU admission were predictors of both 30-day and 90-day mortality. CONCLUSIONS: A high number of patients with COVID-19 had AKI at ICU admission. The study indicates that AKI at ICU admission was related to acute circulatory failure at hospital admission. Age, acute circulatory failure at hospital admission and AKI at ICU admission were associated with mortality.

Magnetic Resonance Spectroscopy in Depressed Subjects Treated With Electroconvulsive Therapy-A Systematic Review of Literature.

Electroconvulsive therapy (ECT) is considered to be the most effective acute treatment for otherwise treatment resistant major depressive episodes, and has been used for over 80 years. Still, the underlying mechanism of action is largely unknow. Several studies suggest that ECT affects the cerebral neurotransmitters, such as gamma-aminobutyric acid (GABA) and glutamate. Magnetic resonance spectroscopy (MRS) allows investigators to study neurotransmitters in vivo, and has been used to study neurochemical changes in the brain of patients treated with ECT. Several investigations have been performed on ECT-patients; however, no systematic review has yet summarized these findings. A systematic literature search based on the Prisma guidelines was performed. PubMed (Medline) was used in order to find investigations studying patients that had been treated with ECT and had undergone an MRS examination. A search in the databases Embase, PsycInfo, and Web of Science was also performed, leading to no additional records. A total of 30 records were identified and screened which resulted in 16 original investigations for review. The total number of patients that was included in these studies, ignoring potential overlap of samples in some investigations, was 325. The metabolites reported were N-acetyl aspartate, Choline, Myoinositol, Glutamate and Glutamine, GABA and Creatine. The strongest evidence for neurochemical change related to ECT, was found for N-acetyl aspartate (reduction), which is a marker of neuronal integrity. Increased choline and glutamate following treatment was also commonly reported.

Assessing ventricular size: is subjective evaluation accurate enough? New MRI-based normative standards for 19-year-olds.

INTRODUCTION: To create new standards for radiological indices of dilated ventricles and to compare these with subjectively assessed ventricular size. METHODS: One hundred healthy controls (54 females), birth weight above 3,000 g, were followed throughout childhood as part of a longitudinal study of ex-prematures. All had a 3 Tesla brain magnetic resonance scan at age 17-20, and the following measurements were performed: biparietal and occipitofrontal diameters, width and depth of the frontal and occipital horns, diameter of the third ventricle and the frontal sub-arachnoid space. Ventricular size was judged subjectively by two neuroradiologists as being normal, or mildly, moderately or severely dilated. RESULTS: Head circumference was 31 mm higher for males than for females (95% confidence interval (CI) 25-28, p < 0.001). Similar, ventricular size except for the depth of the right frontal horn was larger for male; however, the observed differences were partly accounted for by the larger head circumference. Normative sex specific standards for different cerebral measurements were presented as mean and ranges and additional 2.5, 10, 50, 90, 97.5 percentiles. The mean depth of the left ventricle was larger than the right for males, with an observed difference of 0.6 mm in male (95% CI 0.2-0.9, p = 0.005). The mean width of the left ventricle was larger than the right for females, with an observed difference of 0.4 mm in male (95% CI 0.1-0.7, p = 0.018). Two subjects were judged to have moderately and 36 to have mildly dilated ventricles by observer one, while figures for observer two were one and 14. Overall, the two observers agreed on 15 having either mild or moderate dilatation (kappa 0.43). For both sexes, the mean depth of the frontal horns as well as of the larger occipital horns differed significantly between the no dilatation and the mild/moderate dilatation groups. CONCLUSION: In our unselected cohort of healthy 19-year-olds, a high total of 14% was diagnosed to have dilated cerebral ventricles when subjectively assessed by an experienced neuroradiologist, underscoring the need for our new normative standards.

Functional MRI in prenatally opioid-exposed children during a working memory-selective attention task.

BACKGROUND: Opioid induced cerebral changes may contribute to neuropsychological difficulties, like attention problems, frequently reported in prenatally opioid-exposed children. Reduced regional brain volumes have been shown after prenatal opioid exposure, but no study to date has explored the possible impact of prenatal opioids on brain activation patterns. MATERIALS AND METHODS: A hospital-based sample of prenatally opioid-exposed school-aged children (n = 11) and unexposed controls (n = 12) underwent functional magnetic resonance imaging (fMRI) during a combined working memory-selective attention task. Within-group- and between-group analyses of blood-oxygen-level-dependent (BOLD) activation were performed using the SPM12 software package and group differences in task performance were analyzed using Cox proportional hazards modeling. RESULTS: Overall, similar patterns of task related parietal and prefrontal BOLD activations were found in both groups. The opioid-exposed group showed impaired task performance, and during the most cognitive demanding versions of the working memory-selective attention task, increased activation in prefrontal cortical areas was found in the opioid-exposed group compared to controls. CONCLUSION: Our findings suggest that prenatal opioids affect later brain function, visible through changes in BOLD activation patterns. However, results should be considered preliminary until replicated in larger samples better suited to control for potential confounding factors.

Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure.

This study aimed to evaluate cerebral magnetic resonance imaging (MRI) scans of children with prenatal drug exposure in a clinical context. A hospital-based cohort of 10- to 14-year-old children, prenatally exposed to alcohol, opioids, and polysubstances, and a group of sex- and age-matched controls were examined with cerebral MRI. Scans obtained from 34 exposed children and 40 controls were scored based on the presence and degree of pathology by an experienced pediatric neuroradiologist blinded to the participants' background. Overall visual detectable MRI pathology was found in 35% of the exposed children and 33% of the controls (odds ratio = 1.08; 95% confidence interval = 0.36-3.25). No specific imaging pattern following prenatal drug exposure was seen by the means of simple visual analysis of cerebral MRI scans. Although cerebral MRI is feasible, it is probably of limited value in the clinical assessment of children with prenatal drug exposure.

Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study.

BACKGROUND: Both animal and human studies have suggested that prenatal opioid exposure may be detrimental to the developing fetal brain. However, results are somewhat conflicting. Structural brain changes in children with prenatal opioid exposure have been reported in a few studies, and such changes may contribute to neuropsychological impairments observed in exposed children. AIM: To investigate the association between prenatal opioid exposure and brain morphology in school-aged children. STUDY DESIGN: A cross-sectional magnetic resonance imaging (MRI) study of prenatally opioid-exposed children and matched controls. SUBJECTS: A hospital-based sample (n=16) of children aged 10-14years with prenatal exposure to opioids and 1:1 sex- and age-matched unexposed controls. OUTCOME MEASURES: Automated brain volume measures obtained from T1-weighted MRI scans using FreeSurfer. RESULTS: Volumes of the basal ganglia, thalamus, and cerebellar white matter were reduced in the opioid-exposed group, whereas there were no statistically significant differences in global brain measures (total brain, cerebral cortex, and cerebral white matter volumes). CONCLUSIONS: In line with the limited findings reported in the literature to date, our study showed an association between prenatal opioid exposure and reduced regional brain volumes. Adverse effects of opioids on the developing fetal brain may explain this association. However, further research is needed to explore the causal nature and functional consequences of these findings.

High-resolution CT of the chest in children and young adults who were born prematurely: findings in a population-based study.

OBJECTIVE: The purpose of this study was to use a scoring system for high-resolution CT in the evaluation of radiologic findings in young people born extremely preterm and to examine the reproducibility of this scoring system. SUBJECTS AND METHODS: High-resolution CT of the lungs was assessed in 72 children born at a gestational age of < or = 28 weeks or with a birth weight of < or = 1,000 g within a defined region in western Norway in 1982-1985 (n = 40) or in 1991-1992 (n = 32). All images were analyzed by two pediatric radiologists using a scoring system in which a total of 14 features were assessed. RESULTS: Sixty-three (88%) of the subjects had abnormal findings, the most common being linear opacities (n = 52), triangular opacities (n = 42), air trapping (n = 19), and mosaic perfusion (n = 10). Right and left lungs were equally affected. There were fewer abnormalities in the younger age group (born in 1991-1992). Intraobserver agreement and interobserver agreement were moderate (weighted kappa = 0.54 and kappa = 0.52, respectively). Fifty-six of the 72 children had a clinical diagnosis of bronchopulmonary dysplasia, and the median total score and the median scores of the four most common findings were higher in the bronchopulmonary dysplasia group; however, the differences were not statistically significant. CONCLUSION: High-resolution CT in young people of preterm birth revealed abnormal radiologic findings in 81.3% of the patients at age 10 years and 92.5% at age 18 years. Linear, triangular, and subpleural opacities were the most common. The reproducibility of the applied scoring system was acceptable.

F-18-FDG PET-CT in children and young adults with Ewing sarcoma diagnosed in Norway during 2005-2012: a national population-based study.

BACKGROUND: To examine national imaging strategies regarding the use of F-18-FDG PET-CT in patients with Ewing sarcoma and study factors that might influence the use of PET-CT, such as tumour biology (Picci grade of operation specimen), clinical disease stage and age. METHODS: We examined the medical records including pathology and imaging of all patients below 30 years diagnosed with Ewing sarcoma in Norway in 2005-2012. RESULTS: Of 61 patients treated at one of the two national sarcoma treatment service centres (Oslo: 35, Bergen: 26), 29 patients had localized disease, 8 had tumour extending to organs nearby and 24 had metastases. Among 35 operated patients with neoadjuvant chemotherapy, 15 had Picci grades II and III (good responders) and 20 grade I (poor responders). We found a significant difference in the use of PET-CT (Oslo/Bergen 0·9 versus 2·0 scans per patient, P = 0·010) and in the use of MRI (Oslo/Bergen: eight versus 13, P = 0·006). No differences were proven for ultrasound, radiography, CT or skeletal scintigraphy. The number of PET-CTs was associated with clinical disease stage at diagnosis (P = 0·041) but not with Picci grade or age. The number of PET studies was not correlated to the number of MR studies. CONCLUSIONS: The use of PET-CT in children and young adults diagnosed with Ewing sarcoma in Norway during 2005-2012 at the two national sarcoma treatment service centres differed significantly. The use of PET-CT imaging was related to the clinical disease stage at diagnosis but unrelated to patient age and tumour biology (Picci grade).

Cerebral magnetic resonance imaging findings in children born extremely preterm, very preterm, and at term.

BACKGROUND: The aim of this study was to compare findings on cerebral MRI scans of infants born extremely preterm (i.e., gestation < 28 weeks, very preterm; gestation 28-31 weeks) and at term. METHODS: MRI scans obtained in a cohort of 29 extremely preterm children at 11 years, 51 very preterm young adults at 19 years, and respective term-born controls were scored according to presence and degree of MRI pathology. RESULTS: MRI pathology was found in 76% of the extremely preterm children vs 31% of their controls (odds ratio 4.3; 95% confidence interval, 1.5-137.5) and in 55% of the very preterm group vs 19% of their controls (odds ratio 5.2; 95% confidence interval, 2.5-10.9). The distribution of moderate and severe pathology did not differ among the groups. CONCLUSIONS: The extremely preterm, very preterm, and term subjects shared the same morphological pathology, revealing no specific preterm MRI pattern, but both premature cohorts had higher frequencies. Differences were mainly limited to mild pathology. Whether MRI lesions were more common in the extremely preterm than in the very preterm group is uncertain as the difference in frequency was similar in the two control groups, suggesting a lack of objective criteria for differentiating mild pathology from normality or that MRI scans normally differ at 11 and 19 years of age.

Newborns with sonographically dysplastic and potentially unstable hips: 6-year follow-up of an RCT.

OBJECTIVE: To examine the long-term outcome of early abduction splinting versus active sonographic surveillance in newborns with mildly dysplastic hips. PATIENTS AND METHODS: Between 1997 and 2003, 128 newborns with mildly dysplastic and potentially unstable hips on ultrasound (43° ≤ α-angle < 50°) were randomly assigned to immediate abduction treatment or sonographic surveillance. All were invited for a radiographic follow-up at 6 years. The radiographs were analyzed by a single radiologist masked to the randomization allocation, and markers of hip dysplasia (acetabular index, center-edge angle of Wiberg) and avascular necrosis were reported. RESULTS: Eighty-three participants (65%) agreed to participate in the follow-up (42 participants from the treatment group). The mean acetabular index was 14.7° (SD: 5.6°) for the treatment group and 13.9° (SD: 3.9°) for the control group (mean difference: -0.8° [95% confidence interval: -2.9° to 1.3°]). Values were within normal ranges for age for all participants except for 1 female subject from the treatment group. The mean center edge was 26.6° for those treated and 26.4° for the active surveillance group (mean difference: -0.3° [95% confidence interval: -2.5° to 2.0°]). None had markers suggestive of avascular necrosis. CONCLUSIONS: We found no difference in radiographic outcome at 6 years of age between children allocated to initial splintage for 6 weeks and those offered active sonographic surveillance. The delayed acetabular ossification or persistent dysplasia seen in a third of infants from both groups at 1 year of age had completely resolved in all but 1 of the female subjects from the treatment group.

Cerebral MRI and cognition in nonhandicapped, low birth weight adults.

This study sought to compare cognitive and cerebral findings of magnetic resonance imaging in young adults with low birth weights and in a control group. One hundred thirteen of 173 (65%) eligible adults with birth weights <2000 g, and 100 of 170 (59%) controls, all without major disabilities, were examined at age 19 years. Cerebral 3.0 T magnetic resonance imaging was performed according to standardized protocols. Prorated intelligence quotient was estimated from two subtests of the Wechsler Abbreviated Scale of Ability, a word comprehension test, and matrices. Prominent lateral ventricles and loss of white matter, and thinning of the corpus callosum, were more common in the low birth weight group than in the control group (40% vs. 15%, respectively; odds ratio, 3.8; P < 0.001; and 31% vs. 7%, respectively; odds ratio, 6.0; P < 0.001). Low birth weight adults exhibited lower mean intelligence quotients (95 vs. 101, respectively; P < 0.001). Low birth weight adults face an increased risk of prominent ventricles, global loss of white matter, and thinning of the corpus callosum. Similar magnetic resonance imaging findings are not uncommon among healthy adults.

Left vocal cord paralysis after extreme preterm birth, a new clinical scenario in adults.

OBJECTIVE: The goal was to study the incidence and long-term consequences of left vocal cord paralysis (LVCP) after neonatal surgical treatment of patent ductus arteriosus (PDA) in a population-based cohort of adults who were born at gestational ages of ≤28 weeks or with birth weights of ≤1000 g in western Norway. METHODS: Subjects with a history of neonatal PDA surgery were examined with transnasal flexible laryngoscopy, and those with LVCP were examined with continuous laryngoscopy during maximal treadmill exercise (continuous laryngoscopy exercise testing). All subjects underwent lung function testing, ergospirometry, and pulmonary high-resolution computed tomography. Symptoms were recorded with a questionnaire. RESULTS: Forty-four (86%) of 51 eligible preterm infants participated in the study, 13 (26%) had a history of PDA surgery and 7 (54%) had LVCP, with the laryngeal appearances varying slightly. As a group, subjects with LVCP had significant airway obstruction, no decreases in aerobic capacity, and no obvious evidence of longstanding aspiration on high-resolution computed tomography scans. The continuous laryngoscopy exercise tests revealed increasing respiratory symptoms in parallel with increasing anteromedial collapse of the left aryepiglottic folds as the exercise load increased. Hoarseness and voice-related symptoms were the most typical complaints. Symptoms were attributed erroneously to other diseases for at least 2 subjects. CONCLUSIONS: LVCP is not uncommon in young adults exposed to PDA surgery as preterm infants. The condition may be overlooked easily, and symptoms may be confused with those of other diseases. Laryngoscopy should be offered on the basis of liberal indications after PDA ligation.