Adaption of Follow-Up Visits for Preterm and High-Risk Children for Video Consultations.

Introduction: Structured and standardized follow-up care for preterm and high-risk infants enables an early detection of developmental deficits. The aim is to adapt the in-person follow-up to video consultation. Developmental delays can thus be identified at an early stage, independently of in-person contact. Methods: The adaptation of these follow-up to video consultation is presented descriptively, compared with the in-person consultation (similarities, differences, challenges, and limitations). Professionals's experiences with the adaption are described. Results: The experience of n = 267 video consultations for follow-up of children up to 6 years shows that an adaptation of the in-person consultation is necessary and possible. Prerequisite is a digital medium with a stable internet connection on both sides: the professional and the family, as well as a portal for video consultations with certified, encrypted data transmission. Among infants, testing is almost entirely parent guided. For older children, testing procedures have been adapted. A neurological examination is largely possible, while a general pediatric examination is omitted. A survey on professionals' (n = 7) experiences with video- and in-person consultations found that the rate of complete follow-up visits and the resources required for taking medical histories, personnel, and time remained constant for both approaches. All reported that the video consultation is generally suitable for identifying developmental delays in children up to an age of 6 years comparable with in-person consultations. One professional stated that the physical examination of children aged ≥1 year is impossible. Discussion: Video consultation is an alternative despite some limitations when an in-person consultation is impossible. Developmental delays can be identified, and therapies recommended.

Ataxia Rating Scales Reveal Increased Scores in Very Preterm Born 5-6-Year-Old Preschool Children and Young Adults.

The aim of this study is to investigate whether scores in ataxia rating scales (ARS) are different in very preterm (VP) preschool and adult participants compared to term controls. This is a case-control study. Sixty VP children (years: 5.5-6.5; gestational age: 23.9-31.7 weeks) and 56 VP adults (years: 17.8-27.9; gestational age: 23.3-32.0 weeks) without major cerebral lesions participated in the study; 60-age and sex-matched term children and 64 term adults for comparison were used in the study intervened with the assessment with International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA). Main outcome measures are primary outcome: total icars and sara scores in preterm (vp) participants versus controls. Results showed that VP children showed significantly higher total ICARS (M 15.98, SD 6.29, range 4.0-32.0; p < .001) and SARA scores (M 6.5, SD 2.53, range 1.0-15.0; p < .001) than controls (ICARS: M 9.17, SD 3.88, range 2.0-20.0; SARA: M 3.51, SD 1.54, range 1.0-8.0). VP adults also showed significantly higher total ICARS (M 1.0, SD 1.99, range 0.0-11.0; p < .001) and SARA scores (M 0.54, SD 1.08, range 0.0-6.0; p < .001) than controls (ICARS: M 0.11, SD 0.44, range 0.0-2.0; SARA: M 0.04, SD 0.18, range 0.0-1.0). In conclusion, VP children showed significantly higher scores in ARS than controls. These differences were also present in VP adults, suggesting that deficits likely prevail until adulthood. ARS are a time and cost-effective method to screen for difficulties in coordination and balance in a patient group at risk.

Preterm children's long-term academic performance after adaptive computerized training: an efficacy and process analysis of a randomized controlled trial.

BACKGROUND: Adaptive computerized interventions may help improve preterm children's academic success, but randomized trials are rare. We tested whether a math training (XtraMath®) versus an active control condition (Cogmed®; working memory) improved school performance. Training feasibility was also evaluated. METHODS: Preterm born first graders, N = 65 (28-35 + 6 weeks gestation) were recruited into a prospective randomized controlled multicenter trial and received one of two computerized trainings at home for 5 weeks. Teachers rated academic performance in math, reading/writing, and attention compared to classmates before (baseline), directly after (post), and 12 months after the intervention (follow-up). Total academic performance growth was calculated as change from baseline (hierarchically ordered-post test first, follow-up second). RESULTS: Bootstrapped linear regressions showed that academic growth to post test was significantly higher in the math intervention group (B = 0.25 [95% confidence interval: 0.04-0.50], p = 0.039), but this difference was not sustained at the 12-month follow-up (B = 0.00 [-0.31 to 0.34], p = 0.996). Parents in the XtraMath group reported higher acceptance compared with the Cogmed group (mean difference: -0.49, [-0.90 to -0.08], p = 0.037). CONCLUSIONS: Our findings do not show a sustained difference in efficacy between both trainings. Studies of math intervention effectiveness for preterm school-aged children are warranted. IMPACT: Adaptive computerized math training may help improve preterm children's short-term school performance. Computerized math training provides a novel avenue towards intervention after preterm birth. Well-powered randomized controlled studies of math intervention effectiveness for preterm school-aged children are warranted.

Evaluation of 100 brain examinations using a 3 Tesla MR-compatible incubator-safety, handling, and image quality.

INTRODUCTION: Several studies have revealed the importance of brain imaging in term and preterm infants. The aim of this retrospective study was to review safety, handling, and image quality of MR brain imaging using a new 3 Tesla MR-compatible incubator. METHODS: Between 02/2011 and 05/2012 100 brain MRIs (84 infants, mean gestational age 32.2 ± 4.7 weeks, mean postmenstrual age at imaging 40.6 ± 3.4 weeks) were performed using a 3 Tesla MR-compatible incubator with dedicated, compatible head coil. Seventeen examinations (13 infants, mean gestational age 35.1 ± 5.4 weeks, mean postmenstrual age at imaging 47.8 ± 7.4 weeks) with a standard head coil served as a control. Image analysis was performed by a neuroradiologist and a pediatric radiologist in consensus. RESULTS: All but two patients with known apnea were transferred to the MR unit and scanned without problems. Handling was easier and faster with the incubator; relevant motion artifacts (5.9 vs. 10.8%) and the need for repetitive sedation (43.0 vs. 86.7%) were reduced. Considering only images not impaired by motion artifacts, image quality (4.8 ± 0.4 vs. 4.3 ± 0.8, p = 0.047) and spatial resolution (4.7 ± 0.4 vs. 4.2 ± 0.6, p = 0.011) of T2-weighted images were scored significantly higher in patients imaged with the incubator. SNR increased significantly (171.6 ± 54.5 vs. 80.5 ± 19.8, p < 0.001) with the use of the incubator. CONCLUSION: Infants can benefit from the use of a 3 Tesla MR-compatible incubator because of its safety, easier, and faster handling (compared to standard imaging) and possibility to obtain high-quality MR images even in unstable patients.

Early Prediction of Mortality after Birth Asphyxia with the nSOFA.

(1) Birth asphyxia is a major cause of delivery room resuscitation. Subsequent organ failure and hypoxic-ischemic encephalopathy (HIE) account for 25% of all early postnatal deaths. The neonatal sequential organ failure assessment (nSOFA) considers platelet count and respiratory and cardiovascular dysfunction in neonates with sepsis. To evaluate whether nSOFA is also a useful predictor for in-hospital mortality in neonates (≥36 + 0 weeks of gestation (GA)) following asphyxia with HIE and therapeutic hypothermia (TH), (2) nSOFA was documented at ≤6 h of life. (3) A total of 65 infants fulfilled inclusion criteria for TH. All but one infant received cardiopulmonary resuscitation and/or respiratory support at birth. nSOFA was lower in survivors (median 0 [IQR 0-2]; n = 56, median GA 39 + 3, female n = 28 (50%)) than in non-survivors (median 10 [4-12], p < 0.001; n = 9, median GA 38 + 6, n = 4 (44.4%)). This was also observed for the respiratory (p < 0.001), cardiovascular (p < 0.001), and hematologic sub-scores (p = 0.003). The odds ratio for mortality was 1.6 [95% CI = 1.2-2.1] per one-point increase in nSOFA. The optimal cut-off value of nSOFA to predict mortality was 3.5 (sensitivity 100.0%, specificity 83.9%). (4) Since early accurate prognosis following asphyxia with HIE and TH is essential to guide decision making, nSOFA (≤6 h of life) offers the possibility of identifying infants at risk of mortality.

Fear conditioning is preserved in very preterm-born young adults despite increased anxiety levels.

Very preterm birth is associated with an increased risk for anxiety disorders. Abnormal brain development may result in disordered fear learning processes, which may be exacerbated by environmental risk factors and persist in adulthood. We tested the hypotheses that very preterm-born young adults displayed higher levels of fear conditioning, less differentiation between threat (CS+) and safety (CS-) signals, and stronger resistance to extinction relative to term-born controls. A group of 37 very preterm-born young adults and 31 age- and sex-matched term-born controls performed a differential fear conditioning paradigm on two consecutive days. Acquisition and extinction training were performed on day 1. Recall and reinstatement were tested on day 2. Preterm-born participants showed significantly higher levels of anxiety in the Depression-Anxiety-Stress-Scale-21 questionnaire. The fear conditioning outcome measures, skin conductance response amplitudes and anxiety ratings, were overall higher in the preterm-born group compared to controls. Awareness of CS-US contingencies was mildly reduced in preterms. Acquisition, extinction, recall and reinstatement of differential conditioned fear responses (CS+ > CS-), however, were not significantly different between the groups. There were no significant group by stimulus type interactions. The finding of largely preserved associative fear learning in very preterm-born young adults was unexpected and needs to be confirmed in future studies.

General Movements trajectories and outcome at 12 months in very preterm infants: An analysis of tendencies and pathological persistence.

Very preterm infants (VPI) < 32 weeks are at increased risk of developmental disorders detectable using the Prechtl General Movements Assessment (GMA) and the Bayley Scales of Infant and Toddler Development-Third Edition (BSID-III). The aim of this study was to investigate General Movements (GMs) trajectories from preterm to fidgety age including GMs tendencies and their association with cognitive and motor outcome. Retrospective analysis of VPI with GMA at preterm (35 ± 2 weeks postmenstrual age (PMA), T1) and fidgety age (12 ± 3 weeks corrected age CA), T2), and BSID-III (12 ± 3 months CA, T3) is performed. Data are analysed using Pearson χ2-test, Fisher-Freeman-Halton Exact test, and residual analyses. This study found significant associations between (a) GMs (T1) and (b) persistent pathological GMs (T1 + T2) with cognitive outcomes at 12 months (T3) considering the tendencies of GMs in addition to the global character (p = 0.007, p = 0.022, respectively), representing medium-sized effects. There were no significant associations between GMs or persistence of pathological GMs and gross and fine motor outcomes, regardless of GMs tendencies. Findings indicate that considering tendencies of GMs and the persistence of pathological GMs may be important in identifying children at risk of cognitive impairments early. This additional assessment parameter may have the potential for early identification of infants with milder motor and/or cognitive impairments. However, more research is needed using larger sample cohorts to generalise the results and to be able to recommend sequential GMA for clinical routine.

Music therapy modulates mothers' perception of their preterm infants.

Premature birth imposes considerable challenges on the preterm infant, but also challenges the mother, who may not yet be prepared for motherhood and encounter psychological stress during the post-partum period. This secondary analysis of a prospective randomized controlled trial (RCT) aimed to investigate how mothers perceive their preterm infants. We surveyed 33 mothers of preterm infants born before 32 weeks of gestation, who were participating in an RCT on music therapy. We employed the neonatal perception inventory (NPI), an instrument designed to assess the mother's perception and expectations regarding her infant immediately after birth. Infants were randomly assigned to either standard care (control group) or standard care plus music therapy (intervention group). Eighteen mothers from the intervention group participated in the survey (mean age 34.1 ± 4.6 years) and 15 mothers from the control group (mean age 29.6 ± 4.2 years). At the time of the infant's hospital discharge, mothers rated their expectations of how they felt a baby should behave (NPI I) and how they perceived their own infant (NPI II). The NPI score difference was calculated by subtracting the NPI II from the NPI I. Mean NPI I scores were comparable between both groups, but NPI II scores in the intervention group were better [18.0, 95% confidence interval (CI) 16.6-19.4] than in the control group (19.1, 95% CI 18.0-20.3). The relative probability of mothers rating their own baby as better than average was 1.94 (95% CI 1.00-3.79) for mothers whose infants received music therapy. These findings suggest that music therapy in the neonatal intensive care unit can positively influence mothers' perception of their hospitalized preterm infant.

The Impact of Increased Maternal sFlt-1/PlGF Ratio on Motor Outcome of Preterm Infants.

Background: The sFlt-1 (soluble fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio serves as a clinical biomarker to predict the hypertensive, placenta-derived pregnancy disorder pre-eclampsia which is often associated with placental dysfunction and fetal growth restriction. Additionally elevated levels also indicate an increased risk for prematurity. However, its predictive value for subsequent neonatal neurological outcome has not been studied. Objective: This study aimed to evaluate the correlation of maternal sFlt-1/PlGF ratio with early motor outcome of preterm infants. Design/Methods: 88 preterm infants (gestational age ≤ 34 + 0) born between February 2017 and August 2020 at the Department of Obstetrics and Gynecology, University Hospital Essen in Germany, were included, when the following variables were available: maternal sFlt-1/PlGF levels at parturition and general movement assessment of the infant at the corrected age of 3 to 5 months. The infants were stratified into high and low ratio groups according to maternal sFlt-1/PlGF cut-off values of 85. To investigate the early motor repertoire and quality of spontaneous movements of the infant, the Motor Optimality Score (MOS-R) based on antigravity movements and posture patterns, was applied. In the given age, special attention was paid to the presence of fidgety movements. Linear regressions were run to test differences in infants motor repertoire according to the maternal sFlt-1/PIGF ratio. Results: Linear regression analysis showed that the sFlt-1/PlGF ratio does not predict the MOS-R score (ß=≤0.001; p=0.282). However, children with birth weight below the 10th percentile scored significantly lower (mean 20.7 vs 22.7; p=0.035). These children were 91% in the group with an increased ratio, which in turn is a known predictor of low birth weight (ß= -0.315; p <0.001). In the group with a high sFlt-1/PLGF ratio above 85 the mothers of female infants had a lower average sFlt-1/PlGF ratio compared to a male infant (median: 438 in female vs. 603 in male infant, p=0.145). Conclusions: In our cohort, especially low birth weight, which correlated with an elevated sFlt-1/PlGF ratio, had a negative effect on the outcome in the MOS-R. A direct correlation between an increased ratio and a worse motor outcome was not demonstrated.

Impact of Physical Contact on Preterm Infants' Vital Sign Response to Live Music Therapy.

Evidence that music therapy stabilises vital parameters in preterm infants is growing, but the optimal setting for therapy is still under investigation. Our study aimed to quantify the effect of physical contact during live music therapy in preterm infants born < 32 weeks' gestational age (GA) on post-therapy vital sign values. Live music therapy was delivered twice-weekly until discharge from hospital to 40 stable infants < 32 weeks' GA. Baseline and post-therapy heart rate, respiratory rate, oxygen saturation and physical contact during each session were recorded. 159 sessions were performed with, and 444 sessions without, physical contact. Descriptive and multivariable regression analyses based on directed acyclic graphs were performed. The mean GA was 28.6 ± 2.6 weeks, and 26 (65%) infants were male. Mean absolute values for heart and respiratory rates lowered during music therapy regardless of physical contact. The mean post-therapy SaO2 was higher compared to baseline values regardless of physical contact (mean differences −8.6 beats/min; −13.3 breaths/min and +2.0%). There were no clinically relevant changes in vital sign responses between therapy sessions, with or without physical contact, or adjusted post-therapy values for any of the studied vital signs. Physical contact caused better baseline and post-therapy vital sign values but did not enhance the vital sign response to music therapy. Thus, the effect of music therapy on preterm infants' vital signs is independent of physical contact and parents' presence during music therapy in the neonatal intensive care unit.

Music Therapy in Preterm Infants Reduces Maternal Distress.

Preterm delivery is a stressful event for mothers, posing them at risk for post-traumatic stress reactions. This study examined the degree of depressive symptoms and post-traumatic stress in mothers of preterm infants born before 32 gestational weeks depending on whether the infant received music therapy in the neonatal intensive care unit (NICU) or not. We included 33 mothers of preterm infants enrolled in a previously described prospective randomized controlled trial, of whom 18 received music therapy (mean mothers' age 34.1 ± 4.6 years) and 15 did not (mean mothers' age 29.6 ± 4.2). The degree of depressive symptoms, anxiety and acute stress reactions of these mothers were measured by using the German version of the Center for Epidemiologic Studies Depression Scale (CES-D) and Impact of Events Scale-Revised (IES-R) one week after birth (T1) and at infants' hospital discharge (T2). 605 music therapy sessions with a mean duration of 24.2 ± 8.6 min (range 10 to 50 min) were conducted two times a week from the second week of life (T1) until discharge (T2) to the infants from the intervention group. The infants from the control group received standard medical care without music therapy. The mean total CES-D score decreased from T1 (mean 34.7, 95% Confidence Interval (CI) 31.1-38.1) until T2 in all mothers (mean 16.3, 95% CI 12.6-20.1). Mothers whose infants received music therapy showed stronger declines of depressive and stress symptoms (with music therapy: CES-D mean difference of total score 25.7, 95% CI 20.0-31.3, IES-R mean difference of total score 1.7, 95% CI 0.9-2.5, IES-R mean difference of subcategory hyperarousal 10.2, 95% CI 6.2-14.3; without music therapy: CES-D mean difference of total score 9.5, 95% CI 3.8-15.3, IES-R mean difference of total score 0.1, 95% CI -1.0-1.2, IES-R mean difference of subcategory hyperarousal 1.6, 95% CI -4.7-7.9). Effect sizes were strong for CES-D, IES-R, and the hyperarousal subcategory, moderate for intrusion, and low for avoidance. These findings show that mothers of preterm infants are highly susceptible to supportive non-medical interventions such as music therapy to reduce psychological symptoms and distress during their infants' NICU stay.

Parents' Perception of Family-Centered Music Therapy with Stable Preterm Infants.

Premature birth places considerable demands on preterm infants and their families. Most of these infants are treated on a neonatal intensive care unit immediately after birth, leading to psychosocial stress for parents and making it more difficult to build a stable parent-child bond. We hypothesized that accompaniment with live music therapy by a music therapist supports the parents to get in contact with their child and to promote the parents' wellbeing. Preterm infants born at less than 32 gestational weeks received creative music therapy twice a week until discharge. At the time of discharge, the parents were asked to complete a Likert-style questionnaire to evaluate the music therapy. Six items related to socio-demographic characteristics, 4 items to observations on the infant and 10 items to personal perception. Of 40 preterm infants receiving music therapy, 32 (80%) parents completed the questionnaires. Thirty (94%) of these parents were able to relax during the music therapy session. Relaxation in their infants was observed by 29 (91%) during and by 28 (88%) after music therapy. Parents perceived music therapy as a positive change and enrichment during their infant's hospital stay. All parents were thankful for the music therapy they received. Music therapy supports the parents of preterm infants in the first time after birth until discharge from the hospital.

Music Therapy Is Effective during Sleep in Preterm Infants.

Recent research found evidence supporting music therapy for preterm infants to stabilize vital signs and possibly promote neurodevelopment. Even though preterm infants spend a considerable amount of time sleeping, the effectiveness of music therapy during sleep has not been studied. The aim of this study was to investigate the effect of music therapy on preterm infants' vital signs with respect to the state of wakefulness. The first 20 consecutive infants born with <32 weeks' gestational age (GA) from the intervention group of an ongoing randomized controlled trial received live music therapy twice a week until hospital discharge. The heart rate, respiratory rate, oxygen saturation, and state of wakefulness were recorded before and after therapy. We observed significantly lower heart and respiratory rates and higher oxygen saturation after live music therapy sessions in general (mean differences -4.9 beats per min; -7.0 breaths per min and +1.5%, respectively). When music therapy was applied during sleep, respiratory rates significantly lowered by 8.8 breaths per min and oxygen saturation increased by 1.6%, whereas in the awake state the vital parameters did not significantly change (heart rate -5.2 beats per min; respiratory rate +0.6 breaths per min and oxygen saturation +1.0%). Music therapy stabilized the respiratory rates and oxygen saturations in sleeping preterm infants.

Visual Perception, Fine Motor, and Visual-Motor Skills in Very Preterm and Term-Born Children before School Entry-Observational Cohort Study.

Very preterm children (<32 weeks gestation at birth; VP) are at risk of developmental difficulties. Specific functional difficulties and delays in visual perception, fine motor, and visual-motor skills have received little research attention, although they are critical for daily life and school readiness. Our aim was to assess these skills in a contemporary cohort of 60 VP and 60 matched term-born children before school entry. We administered the Movement Assessment Battery for Children (M-ABC-2) and the Developmental Test of Visual Perception (DTVP-2). Linear and logistic regressions were run to test group differences in performance and rates of developmental delay in visual perception, fine motor, and visual-motor skills. Very preterm children had lower scores than term-born children in visual perception (ß = -0.25; p = 0.006), fine motor (ß = -0.44; p < 0.001), and visual-motor tasks (ß = -0.46; p < 0.001). The rate of developmental delay (<-1 SD) was higher among VP in visual perception (odds ratio (OR) = 3.4; 95% confidence interval (CI 1.1-10.6)), fine motor (OR = 6.2 (2.4-16.0)), and visual-motor skills (OR = 13.4 (4.1-43.9)) than in term-born controls. VP children are at increased risk for clinically relevant developmental delays in visual perception, fine motor, and visual-motor skills. Following up VP children until preschool age may facilitate early identification and timely intervention.

Cerebellar-dependent associative learning is impaired in very preterm born children and young adults.

Preterm birth incorporates an increased risk for cerebellar developmental disorders likely contributing to motor and cognitive abnormalities. Experimental evidence of cerebellar dysfunction in preterm subjects, however, is sparse. In this study, classical eyeblink conditioning was used as a marker of cerebellar dysfunction. Standard delay conditioning was investigated in 20 adults and 32 preschool children born very preterm. Focal lesions were excluded based on structural magnetic resonance imaging. For comparison, an equal number of matched term born healthy peers were tested. Subgroups of children (12 preterm, 12 controls) were retested. Preterm subjects acquired significantly less conditioned responses (CR) compared to controls with slower learning rates. A likely explanation for these findings is that preterm birth impedes function of the cerebellum even in the absence of focal cerebellar lesions. The present findings are consistent with the assumption that prematurity results in long-term detrimental effects on the integrity of the cerebellum. It cannot be excluded, however, that extra-cerebellar pathology contributed to the present findings.