Cognitive function in SMA patients with 2 or 3 SMN2 copies treated with SMN-modifying or gene addition therapy during the first year of life.

BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life. METHODS: Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years. RESULTS: 11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome. CONCLUSION: Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions.

Skin Transillumination Improves Peripheral Vein Cannulation by Residents in Neonates: A Randomized Controlled Trial.

INTRODUCTION: Establishing peripheral vein access is challenging for pediatric residents and a painful procedure for neonates. We assessed the efficacy of a red light-emitting diode transilluminator during peripheral vein catheter insertion performed by pediatric residents. METHODS: Patients were stratified by current weight (≤1,500 g, >1,500 g) and randomized to the transillumination or the control group. The first three attempts were performed by pediatric residents, followed by three attempts by a neonatologist. The primary outcome was success at first attempt. Secondary comparisons included time to successful insertion and overall success rates of residents and neonatologists. RESULTS: A total of 559 procedures were analyzed. The success rate at resident's first attempt was 44/93 (47%) with transillumination versus 44/90 (49%) without transillumination (p = 0.88) in the strata ≤1,500 g and 103/188 (55%) with transillumination versus 64/188 (34%) without transillumination in the strata >1,500 g (p < 0.001). The overall success rate for residents was 86% in the transillumination versus 73% in the control group in the strata >1,500 g (p = 0.003) but not different in the strata ≤1,500 g (78/93 [84%] vs. 72/90 [80%], p = 0.57). There was no effect when the experience level of residents exceeded 6 months. Neonatologists' overall success rate and time to successful cannulation did not differ significantly in both weight strata. CONCLUSION: Transillumination improves the first-attempt success rate of peripheral vein cannulation performed by pediatric residents in neonates >1,500 g, while no benefit was found in infants ≤1,500 g.

Effects of liberalising visiting policy and staff education on parental visiting duration in the neonatal unit.

AIM: The effect of different neonatal unit access hour policies on parental visiting duration is unknown. Therefore, we analysed the effects of access hours policies and parental education on parental visiting duration. METHOD: This prospective longitudinal cohort study was carried out in a level III neonatal unit from October 2020 to May 2022. Three cohorts were compared. The baseline cohort included 51 preterm infants with restricted visiting hours (October 2020 to May 2021). Cohort 1 comprised 35 preterm infants after liberalisation of visiting hours (June 2021 to November 2021). Cohort 2 consisted of 26 preterm infants after an educational program was implemented (December 2021 to May 2022). The primary outcome was the mean daily parental visiting duration. RESULTS: Mean maternal visiting duration was 172 (standard deviation, SD ± 49.2), 195 (SD ± 64.4.), and 258 (SD ± 71.1) minutes/day at baseline and in cohorts 1 and 2 (significant increase from baseline and cohort 1 to cohort 2, p < 0.001). Mean paternal visiting duration did not change significantly across the cohorts: 133 (SD ± 47.2), 135 (SD ± 83.5), and 165 (SD ± 71.3) minutes/day. CONCLUSION: Liberalisation of access hours did not increase parental visiting duration. Parental and staff education significantly increased maternal but not paternal visiting duration.

Long-Term Outcome of Infantile Onset Pompe Disease Patients Treated with Enzyme Replacement Therapy - Data from a German-Austrian Cohort.

BACKGROUND: Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) was approved in Europe in 2006. Nevertheless, data on the long-term outcome of infantile onset Pompe disease (IOPD) patients at school age is still limited. OBJECTIVE: We analyzed in detail cardiac, respiratory, motor, and cognitive function of 15 German-speaking patients aged 7 and older who started ERT at a median age of 5 months. RESULTS: Starting dose was 20 mg/kg biweekly in 12 patients, 20 mg/kg weekly in 2, and 40 mg/kg weekly in one patient. CRIM-status was positive in 13 patients (86.7%) and negative or unknown in one patient each (6.7%). Three patients (20%) received immunomodulation. Median age at last assessment was 9.1 (7.0-19.5) years. At last follow-up 1 patient (6.7%) had mild cardiac hypertrophy, 6 (42.9%) had cardiac arrhythmias, and 7 (46.7%) required assisted ventilation. Seven patients (46.7%) achieved the ability to walk independently and 5 (33.3%) were still ambulatory at last follow-up. Six patients (40%) were able to sit without support, while the remaining 4 (26.7%) were tetraplegic. Eleven patients underwent cognitive testing (Culture Fair Intelligence Test), while 4 were unable to meet the requirements for cognitive testing. Intelligence quotients (IQs) ranged from normal (IQ 117, 102, 96, 94) in 4 patients (36.4%) to mild developmental delay (IQ 81) in one patient (9.1%) to intellectual disability (IQ 69, 63, 61, 3x <55) in 6 patients (54.5%). White matter abnormalities were present in 10 out of 12 cerebral MRIs from 7 patients. CONCLUSION: Substantial motor, cardiac, respiratory, and cognitive deficits are frequent in IOPD long-term survivors who started ERT before 2016. The findings of this study can be valuable as comparative data when evaluating the impact of newer treatment strategies including higher enzyme dosage, immunomodulation, modified enzymes, or early start of treatment following newborn screening.

Multidimensional assessment of infant, parent and staff outcomes during a family centered care enhancement project in a tertiary neonatal intensive care unit: study protocol of a longitudinal cohort study.

BACKGROUND: The therapeutic advances and progress in the care for preterm infants have enabled the regular survival of very immature infants. However, the high burden of lifelong sequelae following premature delivery constitutes an ongoing challenge. Regardless of premature delivery, parental mental health and a healthy parent-child relationship were identified as essential prerogatives for normal infant development. Family centered care (FCC) supports preterm infants and their families by respecting the particular developmental, social and emotional needs in the Neonatal Intensive Care Unit. Due to the large variations in concepts and goals of different FCC initiatives, scientific data on the benefits of FCC for the infant and family outcome are sparse and its effects on the clinical team need to be elaborated. METHODS: This prospective single centre longitudinal cohort study enrols preterm infants ≤ 32 + 0 weeks of gestation and/or birthweight ≤ 1500 g and their parents at the neonatal department of the Giessen University Hospital, Giessen, Germany. Following a baseline period, the rollout of additional FCC elements is executed following a stepwise 6-months approach that covers the NICU environment, staff training, parental education and psychosocial support for parents. Recruitment is scheduled over a 5.5. year period from October 2020 to March 2026. The primary outcome is corrected gestational age at discharge. Secondary infant outcomes include neonatal morbidities, growth, and psychomotor development up to 24 months. Parental outcome measures are directed towards parental skills and satisfaction, parent-infant-interaction and mental health. Staff issues are elaborated with particular focus on the item workplace satisfaction. Quality improvement steps are monitored using the Plan- Do- Study- Act cycle method and outcome measures cover the infant, the parents and the medical team. The parallel data collection enables to study the interrelation between these three important areas of research. Sample size calculation was based on the primary outcome. DISCUSSION: It is scientifically impossible to allocate improvements in outcome measures to individual enhancement steps of FCC that constitutes a continuous change in NICU culture and attitudes covering diverse areas of change. Therefore, our trial is designed to allocate childhood, parental and staff outcome measures during the stepwise changes introduced by a FCC intervention program. TRIAL REGISTRATION: Clinicaltrials.gov, trial registration number NCT05286983, date of registration 03/18/2022, retrospectively registered, http://clinicaltrials.gov .

Fluctuations in Oxygen Saturation during Synchronized Nasal Intermittent Positive Pressure Ventilation and Nasal High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants: A Randomized Crossover Trial.

BACKGROUND: Very low birth weight (VLBW) infants on noninvasive ventilation (NIV) experience frequent fluctuations in oxygen saturation (SpO2) that are associated with an increased risk for mortality and severe morbidities. METHODS: In this randomized crossover trial, VLBW infants (n = 22) born 22+3 to 28+0 weeks on NIV with supplemental oxygen were allocated on two consecutive days in random order to synchronized nasal intermittent positive pressure ventilation (sNIPPV) and nasal high-frequency oscillatory ventilation (nHFOV) for 8 h. nHFOV and sNIPPV were set to equivalent mean airway pressure and transcutaneous pCO2. Primary outcome was the time spent within the SpO2 target (88-95%). RESULTS: During sNIPPV, VLBW infants spent significantly more time within the SpO2 target (59.9%) than during nHFOV (54.6%). The proportion of time spent in hypoxemia (22.3% vs. 27.1%) and the mean fraction of supplemental oxygen (FiO2) (29.4% vs. 32.8%) were significantly reduced during sNIPPV, while the respiratory rate (50.1 vs. 42.6) was significantly higher. Mean SpO2, SpO2 above the target, number of prolonged (>1 min) and severe (SpO2 <80%) hypoxemic episodes, parameters of cerebral tissue oxygenation using NIRS, number of FiO2 adjustments, heart rate, number of bradycardias, abdominal distension and transcutaneous pCO2 did not differ between both interventions. CONCLUSIONS: In VLBW infants with frequent fluctuations in SpO2, sNIPPV is more efficient than nHFOV to retain the SpO2 target and to reduce FiO2 exposure. These results demand more detailed investigations into cumulative oxygen toxicities during different modes of NIV over the weaning period, particularly with regard to consequences for long-term outcomes.

Systematic Review on Individualized Versus Standardized Parenteral Nutrition in Preterm Infants.

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of PN.

Neonatal Outcome and Treatment Perspectives of Preterm Infants at the Border of Viability.

Decision-making at the border of viability remains challenging for the expectant parents and the medical team. The preterm infant is dependent on others making the decision that will impact them for a lifetime in hopefully their best interest. Besides survival and survival without neurodevelopmental impairment, other relevant outcome measures, such as the quality of life of former preterm infants and the impact on family life, need to be integrated into prenatal counselling. Recommendations and national guidelines continue to rely on arbitrarily set gestational age limits at which treatment is not recommended, can be considered and it is recommended. These guidelines neglect other individual prognostic outcome factors like antenatal steroids, birth weight and gender. Besides individual factors, centre-specific factors like perinatal treatment intensity and the attitude of healthcare professionals significantly determine the futures of these infants at the border of viability. A more comprehensive approach regarding treatment recommendations and relevant outcome measures is necessary.

New Challenges with Treatment Advances in Newborn Infants with Genetic Disorders and Severe Congenital Malformations.

Advances in the prognosis of relevant syndromes and severe congenital malformations in infants during the last few decades have enabled the treatment and survival of an ever-increasing number of infants, whose prospects were previously judged futile by professional health care teams. This required detailed counselling for families, which frequently started before birth when a diagnosis was made using genetic testing or ultrasound. Predictions of the estimated prognosis, and frequently the more-or-less broad range of prospects, needed to include the chances of survival and data on acute and long-term morbidities. However, in the interest of a having an informed basis for parental decision-making with a professional interdisciplinary team, this process needs to acknowledge the rights of the parents for a comprehensive presentation of the expected quality of life of their child, the potential consequences for family life, and the couple's own relationship. Besides expert advice, professional psychological and familial support is needed as a basis for a well-founded decision regarding the best treatment options for the child. It needs to be acknowledged by the professional team that the parental estimate of a "good outcome" or quality of life does not necessarily reflect the attitudes and recommendations of the professional team. Building a mutually trusting relationship is essential to avoid decision conflicts.

Newborn Septic Arthritis-A Rare Presentation of Late-Onset Group B Streptococcal Disease: Case Report and Short Review of the Literature.

Group B Streptococcus (GBS) disease is a leading cause of invasive bacterial infections among neonates. We present the case of an 11-day-old neonate with septic arthritis as a rare presentation of late-onset disease (LOD) with a favorable short-term outcome. GBS is a leading cause of neonatal infection. Early-onset disease (EOD) is defined as infection from birth to 6 days of age, while LOD occurs from 7 days to approximately 3 months of age. EOD is acquired through vertical transmission and can be reduced through application of intrapartum antibiotic prophylaxis (IAP). LOD can be acquired from the mother or from environmental sources, unlikely to be prevented by IAP. The most common presentation of EOD is bacteremia (83%), pneumonia (9%), and meningitis (7%). While the clinical picture in both EOD and LOD frequently resembles in LOD hamatogenous spreading may predispose neonates to present with uncommon organ manifestation other than the classic systemic signs of sepsis, for example, septic arthritis. Herein, we report on the management and outcome of a term neonate with late onset GqBS bacteremia and subtle clinical symptoms of septic monoarthritis.

Safety and Parental Satisfaction With Early Discharge of Preterm Infants on Nasogastric Tube Feeding and Outpatient Clinic Follow-Up.

Aim: To evaluate our early discharge program of preterm infants with nasogastric tube feeding (NTF) and close outpatient clinic follow-up with regard to safety, parent satisfaction and parental stress level. Methods: 119 preterm infants were discharged on NTF from our tertiary care neonatal unit (median gestational age 31.0 weeks, median birthweight 1,650 g). Parental satisfaction was evaluated by a standardized questionnaire. For safety assessment growth until term equivalent age and re-hospitalizations within 2 months after discharge were evaluated. Results: Infants were discharged home at a median gestational age of 35.4 weeks after a median hospital stay of 22 days. Follow up was attained in 95 of 104 parent-infant dyads. The majority of parents (94%) reported that they had made the right decision in taking their infant home on NTF. At the time of discharge 86% of parents felt very well-prepared to perform NTF. 70% Of parents rated their stress level at home as low (≤2 out of 5). There were no NTF associated readmissions and no growth faltering until term equivalent age. Conclusion: Early discharge of preterm infants with NTF together with outpatient clinic follow-up is very well-accepted by parents and appears to be safe.