Cerebrovascular reactivity to carbon dioxide tension in newborns: data from combined time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy.

Significance: Critically ill newborns are at risk of brain damage from cerebrovascular disturbances. A cerebral hemodynamic monitoring system would have the potential role to guide targeted intervention. Aim: To obtain, in a population of newborn infants, simultaneous near-infrared spectroscopy (NIRS)-based estimates of cerebral tissue oxygen saturation (StO2) and blood flow during variations of carbon dioxide tension (pCO2) levels within physiologic values up to moderate permissive hypercapnia, and to examine if the derived estimate of metabolic rate of oxygen would stay constant, during the same variations. Approach: We enrolled clinically stable mechanically ventilated newborns at postnatal age >24 h without brain abnormalities at ultrasound. StO2 and blood flow index were measured using a non-invasive device (BabyLux), which combine time-resolved NIRS and diffuse-correlation spectroscopy. The effect of changes in transcutaneous pCO2 on StO2, cerebral blood flow (CBF), and cerebral metabolic rate of oxygen index (tCMRO2i) were estimated. Results: Ten babies were enrolled and three were excluded. Median GA at enrollment was 39 weeks and median weight 2720 g. StO2 increased 0.58% (95% CI 0.55; 0.61, p<0.001), CBF 2% (1.9; 2.3, p<0.001), and tCMRO2 0.3% (0.05; 0.46, p=0.017) per mmHg increase in pCO2. Conclusions: BabyLux device detected pCO2-induced changes in cerebral StO2 and CBF, as expected. The small statistically significant positive relationship between pCO2 and tCMRO2i variation is not considered clinically relevant and we are inclined to consider it as an artifact.

Early maternal care restores LINE-1 methylation and enhances neurodevelopment in preterm infants.

BACKGROUND: Preterm birth affects almost 9-11% of newborns and is one of the leading causes of childhood neurodevelopmental disabilities; the underlying molecular networks are poorly defined. In neurons, retrotransposons LINE-1 (L1) are an active source of genomic mosaicism that is deregulated in several neurological disorders; early life experience has been shown to regulate L1 activity in mice. METHODS: Very preterm infants were randomized to receive standard care or early intervention. L1 methylation was measured at birth and at hospital discharge. At 12 and 36 months, infants' neurodevelopment was evaluated with the Griffiths Scales. L1 methylation and CNVs were measured in mouse brain areas at embryonic and postnatal stages. RESULTS: Here we report that L1 promoter is hypomethylated in preterm infants at birth and that an early intervention program, based on enhanced maternal care and positive multisensory stimulation, restores L1 methylation levels comparable to healthy newborns and ameliorates neurodevelopment in childhood. We further show that L1 activity is fine-tuned in the perinatal mouse brain, suggesting a sensitive and vulnerable window for the L1 epigenetic setting. CONCLUSIONS: Our results open the field on the inspection of L1 activity as a novel molecular and predictive approach to infants' prematurity-related neurodevelopmental outcomes. TRIAL REGISTRATION: ClinicalTrial.gov ( NCT02983513 ). Registered on 6 December 2016, retrospectively registered.

Self-Report and Biological Indexes of Work-Related Stress in Neonatal Healthcare Professionals: A Repeated-Measures Observational Study.

BACKGROUND: Healthcare providers working in neonatal intensive care units (NICUs) are considered at high risk for psychological work-related stress. PURPOSE: To evaluate both perceived and biological measures of work-related stress in neonatal healthcare professionals and to compare professionals working in the NICU with their colleagues working in less critical environments (ie, neonatal wards [NWs]). METHODS: The salivary cortisol level at the beginning (CORT-B) and at the end (CORT-E) of a daily work shift was collected once a week for 6 weeks and a psychological questionnaire was submitted to NW and NICU workers of a tertiary university center. RESULTS: No differences emerged in the overall cortisol secretion between professionals (NW 45 vs NICU 28), but the decrease in the mean cortisol values between CORT-B and CORT-E was less pronounced in NICU professionals (P < .001) who had greater psychological stress (P < .001). Lack of correlation between perceived and biological indexes was observed. IMPLICATIONS FOR PRACTICE: NICU professionals reported greater levels of self-perceived psychological stress, especially in terms of professional self-doubt and the complexity of interactions with infants and their parents.The disconnection between psychological and biological indexes raises the issue that work-related stress might be covert to the professionals themselves. Dedicated resources should be developed to address quality of life and the work environment of NICU professionals. IMPLICATIONS FOR RESEARCH: The absence of a correlation between perceived and biological indexes highlights the need to incorporate multidimensional physiological and biological measurements in evaluating burnout levels in neonatal healthcare providers.

Therapeutic potential of stem cells for preterm infant brain damage: Can we move from the heterogeneity of preclinical and clinical studies to established therapeutics?

Acquired perinatal brain injuries are a set of conditions that remains a key challenge for neonatologists and that have significant social, emotional and financial implications for our communities. In our perspective article, we will introduce perinatal brain injury focusing specifically on the events leading to brain damage in preterm born infants and outcomes for these infants. Then we will summarize and discuss the preclinical and clinical studies testing the efficacy of stem cells as neuroprotectants in the last ten years in perinatal brain injury. There are no therapies to treat brain damage in preterm born infants and a primary finding from this review is that there is a scarcity of stem cell trials focused on overcoming brain injuries in these infants. Overall, across all forms of perinatal brain injury there is a remarkable heterogeneity in previous and on-going preclinical and clinical studies in terms of the stem cell type, animal models/patient selection, route and time of administration. Despite the quality of many of the studies this variation makes it difficult to reach a valid consensus for future developments. However, it is clear that stem cells (and stem cell derived exosomes) can reduce perinatal brain injury and our field needs to work collectively to refine an effective protocol for each type of injury. The use of standardized stem cell products and testing these products across multiple models of injury will provide a stronger framework for clinical trials development.

Effects of Early Intervention on Visual Function in Preterm Infants: A Randomized Controlled Trial.

Objectives: To determine the effectiveness of an early intervention program in enhancing visual function in very preterm infants. Methods: We conducted a RCT. We included preterm infants born between 25+0 and 29+6 weeks of gestational age (GA), without severe morbidities, and their families. Infants were randomized to either receive Standard Care (SC) or Early Intervention (EI). SC, according to NICU protocols, included Kangaroo Mother Care and minimal handling. EI included, in addition to routine care, parental training according to the PremieStart program, and multisensory stimulation (infant massage and visual interaction) performed by parents. Visual function was assessed at term equivalent age (TEA) using a prevalidated battery evaluating ocular spontaneous motility, ability to fix and follow a target, reaction to color, stripes discrimination and visual attention at distance. Results: Seventy preterm (EI n = 34, SC n = 36) infants were enrolled. Thirteen were excluded according to protocol. Fifty-seven infants (EI = 27, SC = 30) were assessed at TEA. The two groups were comparable for parental and infant characteristics. In total, 59% of infants in the EI group achieved the highest score in all the nine assessed items compared to 17% in the SC group (p = 0.001): all infants in both groups showed complete maturation in four items, but EI infants showed more mature findings in the other five items (ocular motility both spontaneous and with target, tracking arc, stripes discrimination and attention at distance). Conclusions: Our results suggest that EI has a positive effect on visual function maturation in preterm infants at TEA. Trial Registration: clinicalTrial.gov (NCT02983513).

Effects of in-utero exposure to chemotherapy on fetal brain growth.

OBJECTIVE: Children exposed to chemotherapy in the prenatal period demonstrate normal neurocognitive development at 3 years but concerns regarding fetal brain growth remain high considering its vulnerability to external stimuli. Our aim was to evaluate the impact of in-utero chemotherapy exposure on brain growth and its effects on neurodevelopmental outcome. METHODS: The protocol was approved by the local ethics committee. Brain regional volumes at term postmenstrual age were measured by MRI in children exposed to in-utero chemotherapy and compared with normal MRI controls. Brain segmentation was performed by Advanced Normalization Tools (ANTs)-based transformations of the Neonatal Brain Atlas (ALBERT). Neurodevelopmental assessment (Bayley-III scales) was performed at 18 months corrected age in both exposed infants and in a group of healthy controls. Multiple linear regressions and false discovery rate correction for multiple comparisons were performed. RESULTS: Twenty-one newborns prenatally exposed to chemotherapy (epirubicin administered in 81% of mothers) were enrolled in the study: the mean gestational age was 36.4±2.4 weeks and the mean birthweight was 2,753±622 g. Brain MRI was performed at mean postmenstrual age of 41.1±1.4 weeks. No statistically significant differences were identified between the children exposed to chemotherapy and controls in both the total (398±55 cm3 vs 427±56 cm3, respectively) and regional brain volumes. Exposed children showed normal Bayley-III scores (cognitive 110.2±14.5, language 99.1±11.3, and motor 102.6±7.3), and no significant correlation was identified between the brain volumes and neurodevelopmental outcome. CONCLUSION: Prenatal exposure to anthracycline/cyclophosphamide-based chemotherapy does not impact fetal brain growth, thus supporting the idea that oncological treatment in pregnant women seems to be feasible and safe for the fetus.

Cerebellar Hemorrhage in Preterm Infants: A Meta-Analysis on Risk Factors and Neurodevelopmental Outcome.

Cerebellar hemorrhage (CBH) represents the most commonly acquired lesion of the posterior fossa in the neonatal period. We aimed to perform a systematic review and meta-analysis of studies exploring the perinatal risk factors and neurological outcome of CBH in preterm infants. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE. Studies were included if they examined preterm infants and reported primary data on maternal, obstetric, or perinatal characteristics, and/or outcomes of infants with and without CBH. A random-effects model was used to calculate mean differences (MD), odds ratios (OR), and 95% confidence intervals (CI). We found 231 potentially relevant studies, of which 15 met the inclusion criteria (4,236 infants, 347 CBH cases). Meta-analysis could not demonstrate a significant association between CBH and multiple gestation, chorioamnionitis, pre-eclampsia, placental abruption, use of antenatal corticosteroids, mode of delivery, or infant sex. Infants with CBH had a significantly lower gestational age (6 studies, MD -1.55 weeks, 95% CI -1.93 to -1.16) and birth weight (6 studies, MD -173 g, 95% CI -225 to -120), and significantly higher rates of intubation at birth, hypotension, patent ductus arteriosus, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. CBH was significantly associated with delayed mental (6 studies, OR 2.95, 95% CI 1.21 to 7.20) and psychomotor (6 studies, OR 3.62, 95% CI 1.34 to 9.76) development, and higher rates of cerebral palsy (4 studies, OR 3.09, 95% CI 1.55 to 6.19). In conclusion, the present meta-analysis shows that the youngest and sickest preterm infants are at higher risk of developing CBH. Our results highlight the multifactorial nature of CBH and reinforce the idea that cerebellar injury in very preterm newborns has important neurodevelopmental consequences among survivors.

Cerebral oxygenation and blood flow in term infants during postnatal transition: BabyLux project.

OBJECTIVES: A new device that combines, for the first time, two photonic technologies (time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy) was provided and tested within the BabyLux project. Aim was to validate the expected changes in cerebral oxygenation and blood flow. METHODS: A pulse oximeter and the BabyLux device were held in place (right hand/wrist and frontoparietal region, respectively) for 10 min after birth in healthy term infants delivered by elective caesarean section. Pulse oximeter saturation (SpO2), cerebral tissue oxygen saturation (StO2) and blood flow index (BFI) were measured over time. Tissue oxygen extraction (TOE) and cerebral metabolic rate of oxygen index (CMRO2I) were calculated. RESULTS: Thirty infants were enrolled in two centres. After validity check of data, 23% of infants were excluded from TOE and CMRO2I calculation due to missing data. As expected, SpO2 (estimate 3.05 %/min; 95% CI 2.78 to 3.31 %/min) and StO2 (estimate 3.95 %/min; 95% CI 3.63 to 4.27 %/min) increased in the first 10 min after birth, whereas BFI (estimate -2.84×10-9 cm2/s/min; 95% CI -2.50×10-9 to -3.24×10-9 cm2/s/min) and TOE (estimate -0.78 %/min; 95% CI -1.12 to -0.45 %/min) decreased. Surprisingly, CMRO2I decreased (estimate -7.94×10-8/min; 95% CI -6.26×10-8 to -9.62×10-8/min). CONCLUSIONS: Brain oxygenation and BFI during transition were successfully and simultaneously obtained by the BabyLux device; no adverse effects were recorded, and the BabyLux device did not limit the standard care. The preliminary results from clinical application of the BabyLux device are encouraging in terms of safety and feasibility; they are consistent with previous reports on brain oxygenation during transition, although the interpretation of the decreasing CMRO2I remains open. TRIAL REGISTRATION NUMBER: NCT02815618.

Corrigendum: Chorioamnionitis Is a Risk Factor for Intraventricular Hemorrhage in Preterm Infants: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphys.2018.01253.].

Oxidative Stress and Neonatal Respiratory Extracorporeal Membrane Oxygenation.

Oxidative stress is a frequent condition in critically ill patients, especially if exposed to extracorporeal circulation, and it is associated with worse outcomes and increased mortality. The inflammation triggered by the contact of blood with a non-endogenous surface, the use of high volumes of packed red blood cells and platelets transfusion, the risk of hyperoxia and the impairment of antioxidation systems contribute to the increase of reactive oxygen species and the imbalance of the redox system. This is responsible for the increased production of superoxide anion, hydrogen peroxide, hydroxyl radicals, and peroxynitrite resulting in increased lipid peroxidation, protein oxidation, and DNA damage. The understanding of the pathophysiologic mechanisms leading to redox imbalance would pave the way for the future development of preventive approaches. This review provides an overview of the clinical impact of the oxidative stress during neonatal extracorporeal support and concludes with a brief perspective on the current antioxidant strategies, with the aim to focus on the potential oxidative stress-mediated cell damage that has been implicated in both short and long-term outcomes.

Role of Lung Function Monitoring by the Forced Oscillation Technique for Tailoring Ventilation and Weaning in Neonatal ECMO: New Insights From a Case Report.

Respiratory management during extracorporeal membrane oxygenation (ECMO) is complex. Assessment of lung mechanics might support a patient-tailored ventilatory strategy. We report, for the first time, the use of the forced oscillation technique (FOT) to evaluate lung function during neonatal ECMO to improve the individualization of respiratory support. The patient was a formerly preterm infant at a corrected age of 40 weeks (gestational age 32 weeks) undergoing veno-arterial ECMO for refractory respiratory failure secondary to influenza A (H1N1) pneumonia. We used the FOT as a bedside non-invasive tool for daily monitoring of lung mechanics, from ECMO day 6 (E6) until decannulation. A small-amplitude, 5-Hz oscillatory pressure was overimposed on the ventilation waveform at the airway opening during positive end-expiratory pressure (PEEP) trials. From E6 to E9, lung mechanics changes with PEEP indicated a largely de-recruited and easily over-distendable lung that was not recruitable by applying lung-protective PEEP values. After surfactant and steroid administration, oscillatory reactance (Xrs) values began improving, suggesting a more recruited and pressure-recruitable lung. On E11, despite the lack of improvement in the radiographic appearance of the thorax, the FOT measurements showed a more recruited lung. Weaning from ECMO was started, and the patient was extubated within 48 h. The decannulation was successful, and the patient was extubated within 48 h after ECMO weaning. First-year respiratory and neurodevelopmental follow-up evaluation was unremarkable. This report suggests the potential usefulness of the FOT for monitoring the lung mechanics of ventilated newborns during ECMO to achieve individualized respiratory management. Such tailoring might improve neonatal outcomes and support clinicians with the establishment of a timely and safer weaning approach. These findings need to be verified on a larger population.

Chorioamnionitis Is a Risk Factor for Intraventricular Hemorrhage in Preterm Infants: A Systematic Review and Meta-Analysis.

Although chorioamnionitis (CA) is a well-known risk factor for white matter disease of prematurity, the association with intraventricular hemorrhage (IVH) is controversial and has not been yet systematically reviewed. We performed a systematic review and meta-analysis of studies exploring the association between CA and IVH. A comprehensive literature search was conducted using PubMed/MEDLINE and EMBASE, from their inception to 1 July 2017. Studies were included if they examined preterm infants and reported primary data that could be used to measure the association between exposure to CA and the presence of IVH. A random-effects model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). We found 1,284 potentially relevant studies, of which 85 met the inclusion criteria (46,244 infants, 13,432 CA cases). Meta-analysis showed that CA exposure was significantly associated with all grades IVH (OR 1.88, 95% CI 1.61-2.19), with grades 1-2 IVH (OR 1.69, 95% CI 1.22-2.34), and with grades 3-4 IVH (OR 1.62, 95% CI 1.42-1.85). Both clinical and histological CA were associated with an increased risk for developing IVH in very preterm infants. In contrast, the presence of funisitis did not increase IVH risk when compared to CA in the absence of funisitis (OR 1.22, 95% CI 0.89-1.67). Further meta-analyses confirmed earlier findings that CA-exposed infants have significantly lower gestational age (GA; mean difference [MD] -1.20 weeks) and lower birth weight (BW; MD -55 g) than the infants not exposed to CA. However, meta-regression and subgroup analysis could not demonstrate an association between the lower GA and BW and the risk of IVH in the CA-exposed infants. In conclusion, our data show that CA is a risk factor for IVH, but also a risk factor for greater prematurity and more clinical instability. In contrast to other complications of prematurity, such as patent ductus arteriosus, retinopathy of prematurity, or bronchopulmonary dysplasia, the effect of CA on IVH appears to be independent of CA as causative factor for very preterm birth.

Start a Neonatal Extracorporeal Membrane Oxygenation Program: A Multistep Team Training.

Background: Extracorporeal membrane oxygenation (ECMO) is a complex life-saving support for acute cardio-respiratory failure, unresponsive to medical treatment. Emergency events on ECMO are rare but require immediate and proficient management. Multidisciplinary ECMO team members need to acquire and maintain over time cognitive, technical and behavioral skills, to safely face life-threatening clinical scenarios. Methods: A multistep educational program was delivered in a 4-year period to 32 ECMO team members, based on guidelines from the Extracorporeal Life Support Organization. A first traditional module was provided through didactic lectures, hands-on water drills, and laboratory animal training. The second phase consisted of a multi-edition high-fidelity simulation-based training on a modified neonatal mannequin (SimNewB®). In each session, participants were called to face, in small groups, ten critical scenarios, followed by debriefing time. Trainees underwent a pre-test for baseline competency assessment. Once completed the full training program, a post-test was administered. Pre- and post-test scores were compared. Trainees rated the educational program through survey questionnaires. Results: 28 trainees (87.5%) completed the full educational program. ECMO staff skills improved from a median pre-test score of 7.5/18 (IQR = 6-11) to 14/18 (IQR = 14-16) at post-test (P < 0.001, Wilcoxon rank test). All trainees highly rated the educational program and its impact on their practice. They reported high-fidelity simulations to be beneficial to novice learners as it increased self-confidence in ECMO-emergencies (according to 100% of surveyed), theoretical knowledge (61.5%) and team-work/communicative skills (58%). Conclusions: The multistep ECMO team training increased staff' knowledge, technical skills, teamwork, and self-confidence, allowing the successful development of a neonatal respiratory ECMO program. Conventional training was perceived as relevant in the early phase of the program development, while the active learning emerged to be more beneficial to master ECMO knowledge, specific skills, and team performance.

Effects of early intervention on feeding behavior in preterm infants: A randomized controlled trial.

BACKGROUND: Although highly beneficial, human milk feeding is challenging in preterm infants due to adverse NICU factors for the infant and mother. AIM: To investigate the effects of an early intervention in promoting infant's human milk feeding and acquisition of full oral feeding. METHODS: This study is part of a RCT. We included preterm infants born between 25+0 and 29+6 weeks of gestational age (GA) without severe morbidities, and their parents. Infants were randomized to either receive early intervention (EI) or standard care (SC). EI included PremieStart and parental training to promote infant massage and visual attention according to a detailed protocol. SC, in line with NICU protocols, included Kangaroo Mother Care. The time of acquisition of full oral feeding and human milk consumption at discharge were recorded. RESULTS: Seventy preterm (EI n = 34, SC n = 36) infants were enrolled. Thirteen were excluded according to the protocol. Fifty-seven (EI n = 29, SC n = 28) infants were evaluated at discharge. The two groups were comparable for parent and infant characteristics. A significantly higher rate of infants fed with any human milk was observed in the EI group (75.9%) compared with the SC group (32.1%) (p = 0.001), and EI infants were four times more likely to be fed exclusively with human milk. Full oral feeding was achieved almost one week earlier in EI infants (mean postmenstrual age 36.8 ±â€¯1.6 vs 37.9 ±â€¯2.4 weeks in EI vs SC, p = 0.04). CONCLUSIONS: Early interventions promoting mother self-efficacy and involvement in multisensory stimulation have beneficial effects on human milk feeding in preterm infants.

The Impact of Twin Birth on Early Neonatal Outcomes.

OBJECTIVE: This study aims to describe the impact of twin birth, chorionicity, intertwin birth weight (BW) discordance and birth order on neonatal outcomes. STUDY DESIGN: We performed a hospital-based retrospective study on 2,170 twins (6.4% of all live births) and 2,217 singletons inborn 2007 to 2011. Data on neonatal characteristics, morbidities, and mortality were collected and compared. Univariate and multiple (adjusted for gestational age [GA] and gender) linear random intercept regression models were used. RESULTS: Overall, 62.3% of twins were born premature. At multiple regression, twins were similar to singletons for neonatal morbidities, but they were more likely to have lower BW and to be born by cesarean delivery. Monochorionic twins had lower GA and BW compared with dichorionic ones and were more likely to develop respiratory distress syndrome (odds ratio [OR], 1.7), hypoglycemia (OR, 3.3), need for transfusion, (OR, 3.4) but not brain abnormalities. Moderate and severe BW discordance were associated with longer length of stay and increased risk for morbidities but not for death. Birth order had no effects. CONCLUSION: Prematurity was the most common outcome in twins and accounted for the apparently increased risk in morbidities. Monochorionicity was confirmed as risk factor for lower GA and neonatal morbidities. BW discordance may play a role in developing neonatal complications and needs to be further investigated.

Intracranial haemorrhage: an incidental finding at magnetic resonance imaging in a cohort of late preterm and term infants.

BACKGROUND: Intracranial haemorrhage (ICH) in term newborns has been increasingly recognised but the occurrence in late preterm infants and the clinical presentation are still unclear. OBJECTIVE: To investigate the appearance of intracranial haemorrhage at MRI in a cohort of infants born at 34 weeks' gestation or more and to correlate MRI findings with neonatal symptoms. MATERIALS AND METHODS: We retrospectively reviewed neonatal brain MRI scans performed during a 3-year period. We included neonates ≥34 weeks' gestation with intracranial haemorrhage and compared findings with those in babies without intracranial haemorrhage. Babies were classified into three groups according to haemorrhage location: (1) infratentorial, (2) infra- and supratentorial, (3) infra- and supratentorial + parenchymal involvement. RESULTS: Intracranial haemorrhage was observed in 36/240 babies (15%). All of these 36 had subdural haemorrhage. Sixteen babies were included in group 1; 16 in group 2; 4 in group 3. All infants in groups 1 and 2 were asymptomatic except one who was affected by intraventricular haemorrhage grade 3. Among the infants in group 3, who had intracranial haemorrhage with parenchymal involvement, three of the four (75%) presented with acute neurological symptoms. Uncomplicated spontaneous vaginal delivery was reported in 20/36 neonates (56%), vacuum extraction in 4 (11%) and caesarean section in 12 (33%). Babies with intracranial haemorrhage had significantly higher gestational age (38 ± 2 weeks vs. 37 ± 2 weeks) and birth weight (3,097 ± 485 g vs. 2,803 ± 741 g) compared to babies without intracranial haemorrhage and were more likely to be delivered vaginally than by caesarian section. CONCLUSION: Mild intracranial haemorrhage (groups 1 and 2) is relatively common in late preterm and term infants, although it mostly represents an incidental finding in clinically asymptomatic babies; early neurological symptoms appear to be related to parenchymal involvement.

Vaccination in patients with disorders of the muscle and neuromuscular junction.

Neuromuscular diseases cover a broad spectrum of conditions that have important differences. Infections are frequently associated with severe complications, mainly because the neurological involvement can cause the aspiration of respiratory secretions and be significantly worsened by progressive respiratory and/or cardiovascular disease and immunosuppressive therapy. Preventing infectious diseases in patients with disorders of the muscle and neuromuscular junction is clinically important and vaccines play an important role in this regard. The majority of experts recommend that patients with these disorders should receive the same vaccinations as those recommended for healthy subjects, with special attention being given to the fact that two doses of measles, mumps, rubella (MMR) and varicella vaccines should be administered before beginning immunosuppressive therapy. In addition, annual influenza vaccination and pneumococcal vaccination are recommended for almost all patients with disorders of the muscle and neuromuscular junction.