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AimTo assess the inter-assessor reliability of the Motor Optimality Score-Revised (MOS-R) when used in infants at elevated likelihood for adverse neurological outcome.MethodsMOS-R were assessed in three groups of infants by two assessors/cohort. Infants were recruited from longitudinal projects in Sweden (infants born extremely preterm), India (infants born in low-resource communities) and the USA (infants prenatally exposed to SARS-CoV-2). Intraclass correlation coefficients (ICC) and kappa (κw) were applied. ICC of MOS-R subcategories and total scores were presented for cohorts together and separately and for age-spans: 9-12, 13-16 and 17-25-weeks post-term age.Results252 infants were included (born extremely preterm n = 97, born in low-resource communities n = 97, prenatally SARS-CoV-2 exposed n = 58). Reliability of the total MOS-R was almost perfect (ICC: 0.98-0.99) for all cohorts, together and separately. Similar result was found for age-spans (ICC: 0.98-0.99). Substantial to perfect reliability was shown for the MOS-R subcategories (κw: 0.67-1.00), with postural patterns showing the lowest value 0.67.ConclusionThe MOS-R can be used in high-risk populations with substantial to perfect reliability, both in regards of total/subcategory scores as well as in different age groups. However, the subcategory postural patterns as well as the clinical applicability of the MOS-R needs further study.

The study aim was to explore the relationship between a developmental assessment at preschool age and an intelligence quotient (IQ) assessment at school age. One hundred sixty-two children were assessed at 2.5 years with the Bayley Scales of Infant and Toddler Development--Third Edition (Bayley-III) and then at 6.5 years with the Wechsler Intelligence Scale for Children--Fourth Edition (WISC-IV). The Bayley-III Cognitive Index score was the Bayley entity that showed the highest correlation with WISC-IV Full-Scale IQ (FSIQ; r = 0.41). There was a significant difference between the individual WISC-IV FSIQ and the Bayley-III Cognitive Index scores. Analyses showed an average difference of -4 units and 95% limits of agreement of -18.5 to 26.4 units. A multivariate model identified the Bayley-III Cognitive Index score as the most important predictor for FSIQ and General Ability Index (GAI), respectively, in comparison with demographic factors. The model explained 24% of the total FSIQ variation and 26% of the GAI variation. It was concluded that the Bayley-III measurement was an insufficient predictor of later IQ.

Background Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N  = 3635). Results Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks' gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. Conclusions Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age. [ABSTRACT FROM AUTHOR]

Background: Anakinra and tocilizumab are used for severe Covid-19, but only one previous randomized controlled trial (RCT) has studied both. We performed a multi-center RCT comparing anakinra or tocilizumab versus usual care (UC) for adults at high risk of deterioration. Methods: The study was conducted June 2020 to March 2021. Eligibility required ≥ 5 liters/minute of Oxygen to maintain peripheral oxygen saturation at ≥ 93%, CRP > 70 mg/L, ferritin > 500 μg/L and at least two points where one point was awarded for lymphocytes < 1x 109/L; D-dimer ≥ 0.5 mg/L and; lactate dehydrogenase ≥ 8 microkatal/L. Patients were randomly assigned 1:1:1 to receive either a single dose of tocilizumab (8 mg/kg) or anakinra 100 mg IV QID for seven days or UC alone. The primary outcome was time to recovery. Results: Recruitment was ended prematurely when tocilizumab became part of usual care. Out of a planned 195 patients, 77 had been randomized, 27 to UC, 28 to anakinra and 22 to tocilizumab. Median time to recovery was 15, 15 and 11 days. Rate ratio for recovery for UC vs anakinra was 0.91, 0.47 to 1.78, 95% [CI], p = 0.8 and for UC vs tocilizumab 1.13, 0.55 to 2.30; p = 0.7. There were non-significant trends favoring tocilizumab (and to limited degree anakinra) vs UC for some secondary outcomes. Safety profiles did not differ significantly. Conclusion: Premature closure of trial precludes firm conclusions. Anakinra or tocilizumab did not significantly shorten time to clinical recovery compared to usual care. (IMMCoVA, NCT04412291, EudraCT: 2020–00174824). [ABSTRACT FROM AUTHOR]

Introduction: The risk for brain injury manifested as cerebral palsy is higher in very preterm born children than in term. Prenatal administration of magnesium sulfate (MgSO4) has been shown to be neuroprotective and reduces the proportion of very preterm born children later diagnosed with cerebral palsy. A Swedish national clinical practice guideline was implemented in March 2020, stipulating the administration of a single intravenous dose of 6 g MgSO4 1–24 h prior to delivery before gestational age 32+0, aiming for 90% treatment coverage. The aim of this study was to evaluate the feasibility of this new clinical practice guideline in the first year of its implementation. Material and methods: Data on MgSO4 treatment were collected by reviewing the medical charts of women who gave birth to live born children in gestational age 22+0–31+6 during the period of March 1, 2020 to February 28, 2021, at five Swedish university hospitals. Women with pre‐eclampsia, eclampsia, or high elevated liver enzymes low platelets (HELLP) were excluded. Results: A total of 388 women were eligible and 79% received treatment with MgSO4. Of the 21% not receiving treatment, 9% did not receive treatment due to lack of knowledge about the clinical practice guideline, 9% were not possible to treat and 3% had missing data. The proportion treated increased from 72% to 87% from the first to the last 3 months. Of those treated, 81% received the drug within the stipulated timeframe (mean 8.7 h, median 3.4 h). Conclusions: There was a positive trend over time in the proportion of women receiving MgSO4 treatment, but the a priori target of 90% was not reached during the first year of implementation. Our findings indicate that this target could be reached with additional information to clinicians. [ABSTRACT FROM AUTHOR]

Aim: To measure the association between cerebral palsy (CP) and non‐CP‐related movement difficulties and health‐related quality of life (HRQoL) among 5‐year‐old children born extremely preterm (<28 weeks gestational age). Method: We included 5‐year‐old children from a multi‐country, population‐based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (≤5th centile of standardized norms) or being at risk of movement difficulties (6th–15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. Results: Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (β [95% confidence interval] = −5.0 [−7.7 to −2.3], −9.1 [−12.0 to −6.1], and − 26.1 [−31.0 to −21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non‐CP‐related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. Interpretation: CP and non‐CP‐related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non‐CP‐related movement difficulties raise questions for research about mitigating and protective factors. This original article is commented on by Evensen on pages 1546–1547 of this issue. [ABSTRACT FROM AUTHOR]

Aim: To determine the prevalence of neurobehavioral symptoms at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation). Methods: Population‐based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term‐born controls. EPT children free from neurosensory and intellectual disabilities (neurodevelopmental disabilities [NDD]‐free, n = 236) were compared separately. Standardised questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer‐relation, conduct and social problems; and deficits in perception, language and memory. Results: EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than three times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD–free children. The odds of having neurobehavioral problems in ≥3 co‐occurring domains were five (whole EPT group) and three (NDD‐free group) times higher than in controls. Conclusion: EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behaviour until school age or beyond should recognise early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties. [ABSTRACT FROM AUTHOR]

Aim: To assess the predictive validity of parent‐reported gross motor impairment (GMI) at age 2 years to detect significant movement difficulties at age 5 years in children born extremely preterm. Method: Data were from 556 children (270 males, 286 females) born at less than 28 weeks' gestation in 2011 to 2012 in 10 European countries. Parent report of moderate/severe GMI was defined as walking unsteadily or unable to walk unassisted at 2 years corrected age. Examiners assessed significant movement difficulties (score ≤ 5th centile on the Movement Assessment Battery for Children, Second Edition) and diagnoses of cerebral palsy (CP) were collected by parent report at 5 years chronological age. Results: At 2 years, 66 (11.9%) children had moderate/severe GMI. At 5 years, 212 (38.1%) had significant movement difficulties. Parent reports of GMI at age 2 years accurately classified CP at age 5 years in 91.0% to 93.2% of children. Classification of moderate/severe GMI at age 2 years had high specificity (96.2%; 95% confidence interval 93.6–98.0) and positive predictive value (80.3%; 68.7–89.1) for significant movement difficulties at age 5 years. However, 74.5% of children with significant movement difficulties at 5 years were not identified with moderate/severe GMI at age 2 years, resulting in low sensitivity (25.1%; 19.4–31.5). Interpretation: This questionnaire may be used to identify children born extremely preterm who at age 2 years have a diagnosis of CP or movement difficulties that are likely to have a significant impact on their functional outcomes at age 5 years. [ABSTRACT FROM AUTHOR]

Aim: Studies examining the long‐term effects of neonatal music interventions on the cognition of children born preterm are scarce. We investigated whether a parental singing intervention before term age improves cognitive and language skills in preterm‐born children. Methods: In this longitudinal, two‐country Singing Kangaroo, randomised controlled trial, 74 preterm infants were allocated to a singing intervention or control group. A certified music therapist supported parents of 48 infants in the intervention group to sing or hum during daily skin‐to‐skin care (Kangaroo care) from neonatal care until term age. Parents of 26 infants in the control group conducted standard Kangaroo care. At 2–3 years of corrected age, the cognitive and language skills were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. Results: There were no significant differences in cognitive and language skills between the intervention and control groups at the follow‐up. No associations between the amount of singing and the cognitive and language scores were found. Conclusion: Parental singing intervention during the neonatal period, previously shown to have some beneficial short‐term effects on auditory cortical response in preterm infants at term age, showed no significant long‐term effects on cognition or language at 2–3 years of corrected age. [ABSTRACT FROM AUTHOR]

Objective: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group. Methods: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age- specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term. Results: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05). Conclusions: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between gestational age at birth and risk of clinically diagnosed intellectual disability (ID) week by week to provide a detailed description of ID risk across the entire range of gestational ages and by severity of ID.Methods: All individuals born alive in Sweden 1974-2017 were prospectively followed up from birth until 2017 using national registers. The HRs for ID according to weekly gestational age and gestational age categories were determined using Cox models. Sibling analyses were conducted to adjust for familial confounding.Results: The study included 3 572 845 live births. During the follow-up, 26 596 ID cases were registered. The adjusted weekly estimates showed a gradual increase in risk of ID from week 40 to week 24 (adjusted HR37weeks=1.80 (1.74 to 1.87), aHR32weeks=3.93 (3.73 to 4.13), aHR28weeks=7.53 (6.95 to 8.16), aHR24weeks=21.58 (18.62 to 25.00)) and from week 41 onwards (aHR42weeks=1.26 (1.19 to 1.32)), with statistically significantly higher risks across the range of gestational age compared with infants born at week 40. The associations were consistent in mild, moderate and severe/profound ID but most prominent for severe/profound ID.Conclusion: The risk of ID increased weekly as the date of delivery moved away from 40 weeks, both preterm and post-term. The results remained robust after detailed adjustment for confounding, including familial confounding. [ABSTRACT FROM AUTHOR]

Aim: To (1) determine the proportion of 5‐year‐old children born extremely preterm (EPT) with movement difficulties including cerebral palsy (CP) and the proportion of these children receiving motor‐related health care (MRHC), and (2) describe factors associated with receiving MRHC. Method: Children born before 28 weeks' gestation in 2011 to 2012 in 11 European countries were assessed with the Movement Assessment Battery for Children, Second Edition (MABC‐2) at 5 years of age. Information on family characteristics, child health including CP diagnosis, and health care use were collected using parent‐report questionnaires. MRHC was defined as visits in the previous year with health care providers (physical and occupational therapists) specialized in assessing/treating motor problems. We analysed receipt of MRHC and associated factors among children at risk of movement difficulties (MABC‐2 score 6th–15th centiles), with significant movement difficulties (SMD; ≤5th centile) or with CP. Results: Of 807 children assessed at 5 years 7 months (SD 4 months; 4 years 7 months–7 years 1 month), 412 were males (51.1%), 170 (21.1%) were at risk of movement difficulties, 201 (24.9%) had SMD, and 92 (11.4%) had CP. Those who received MRHC comprised 89.1% of children with CP, 42.8% with SMD, and 25.9% at risk of movement difficulties. MRHC for children with SMD varied from 23.3% to 66.7% between countries. Children were more likely to receive MRHC if they had other developmental problems or socioemotional, conduct, or attention difficulties. Interpretation: Efforts are needed to increase MRHC for 5‐year‐old children born EPT with movement difficulties. What this paper adds: Children born extremely preterm without cerebral palsy frequently experienced motor difficulties.Most of these children were not receiving motor‐related health care (MRHC).Large geographical differences throughout Europe were observed in receipt of MRHC.Socioemotional problems were related to MRHC use. [ABSTRACT FROM AUTHOR]

As the human auditory system is highly malleable in infancy, perinatal risk factors, such as preterm birth, may affect auditory development. In comparison to healthy full-term infants, preterm infants show abnormal auditory brain responses at term age, which may have long-term detrimental outcomes. To achieve an optimal neonatal care environment for preterm-born infants, many early interventions have been developed. Musical interventions developed for neonatal intensive care units (NICUs) have shown beneficial effects on vital functions and weight gain of preterm infants and might also influence basic auditory processing and thereby enhance outcomes. In the present study, we tested the effect of parental singing during kangaroo care on auditory processing of standardized audio stimuli. Preterm infants (born between 24 and 32 weeks of gestation) were randomized to singing intervention (n = 13) or control (n = 8) groups. The auditory processing was tested using two audio paradigms assessed with magnetoencephalography (MEG) at term corresponding age. To verify that the paradigms elicit responses in MEG, we studied 12 healthy full-term infants. In the singing intervention group, parents were instructed by a music therapist twice a week for 4 weeks to sing or hum during kangaroo care in an infant-directed way. The control group received standard kangaroo care. The results show that the infants in the singing intervention group show larger neural responses than those in the control group when controlling for the total amount of singing during kangaroo care. Our findings suggest that incorporating singing into kangaroo care may be beneficial for preterm infants, but the effect may not be due to exposure to singing but instead positive parenting, improved parental self-esteem and improved caregiver sensitivity. [ABSTRACT FROM AUTHOR]

Aim: Little is known about the prevalence of discrete white matter abnormalities (WMA) beyond the first years in children born extremely preterm (EPT) and the relation to neurodevelopmental outcomes. Our aim was to investigate the prevalence of discrete WMA in children born EPT and the relationship to neonatal white matter injuries (WMI), white matter (WM) volume, WM diffusivity and neurodevelopment. Methods: The study was a part of a longitudinal follow‐up study of EPT neonates. All children were scanned at Karolinska University hospital 2004–2007 (neonates) and 2014–2015 (children at 8–11 years). WMA was qualitatively assessed by visual inspection. Developmental assessment was conducted at 12 years. Results: In total, 112 children (median age 10.3 years, 56 girls) underwent MRI of the brain (68 EPT, 45 controls). In the EPT group, a subset had MRI around term equivalent age (n = 61). In the EPT group, the prevalence of discrete WMA at 8–11 years was 52%. There was a positive association between WMI at TEA and 8–11 years. There was no association between WMI and WM volumes or diffusivity at 8–11 years. Discrete WMA was not related to neurodevelopmental outcomes. Conclusion: Discrete WMA was prevalent in children born EPT at 8–11 years but were not related to neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. Study design: Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. Results: At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of −8.4 to −1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of −10.9 to −1.0 (p = 0.010). Conclusion: Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls. [ABSTRACT FROM AUTHOR]

Aim: To investigate the ability of the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), scores to predict later Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), performances in a cohort of children born extremely preterm.Methods: 323 children, born <27 gestational weeks, were tested with the Bayley-III at corrected age 2.5 years and with the WISC-IV at 6.5 years. Regression analyses investigated the association between Bayley-III scores and WISC-IV full-scale intelligence quotient (IQ). The ability of Bayley-III Cognitive Index scores to predict low IQ was evaluated using receiver operating characteristic curves.Results: Bayley-III Cognitive Index scores and IQ had a moderately positive correlation and accounted for 38% of the IQ variance. Using a Bayley-III cut-off score of 70, the sensitivity to detect children with IQ<70 was 18%, and false positive rate was 7%. A Bayley-III cut-off score of 85 corresponded to sensitivity and false positive rates of 44% and 7%, respectively.Conclusions: Results emphasise the relative importance of Bayley-III Cognitive Index scores as predictors of IQ. An 85 score cut-off for suspecting subnormal IQ is supported. A less conservative threshold would increase identification of true cases yet increase the risk of wrongly diagnosing children. [ABSTRACT FROM AUTHOR]