BACKGROUNDSpinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. METHODSWe conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. RESULTSIn the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P = 0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P = 0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. CONCLUSIONSAmong infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074.)

Aim To provide a comprehensive update on the most prevalent, significant risk factors for neonatal brachial plexus palsy (NBPP). Method Cochrane CENTRAL, MEDLINE, Web of Science, Embase, and ClinicalTrials.gov were searched for relevant publications up to March 2019. Studies assessing risk factors of NBPP in relation to typically developing comparison individuals were included. Meta‐analysis was performed for the five most significant risk factors, on the basis of the PRISMA statement and MOOSE guidelines. Pooled odds ratios (ORs), 95% confidence intervals (CIs), and across‐study heterogeneity (I2) were reported. Reporting bias and quality of evidence was rated. In addition, we assessed the incidence of NBPP. Results Twenty‐two observational studies with a total sample size of 29 419 037 live births were selected. Significant risk factors included shoulder dystocia (OR 115.27; 95% CI 81.35–163.35; I2=92%), macrosomia (OR 9.75; 95% CI 8.29–11.46; I2=70%), (gestational) diabetes (OR 5.33; 95% CI 3.77–7.55; I2=59%), instrumental delivery (OR 3.8; 95% CI 2.77–5.23; I2=77%), and breech delivery (OR 2.49; 95% CI 1.67–3.7; I2=70%). Caesarean section appeared as a protective factor (OR 0.13; 95% CI 0.11–0.16; I2=41%). The pooled overall incidence of NBPP was 1.74 per 1000 live births. It has decreased in recent years. Interpretation The incidence of NBPP is decreasing. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are risk factors for NBPP. Caesarean section appears as a protective factor. What this paper adds The overall incidence of neonatal brachial plexus palsy is 1.74 per 1000 live births. The incidence has declined significantly. Shoulder dystocia, macrosomia, maternal diabetes, instrumental delivery, and breech delivery are the main risk factors. Prevention is difficult owing to unpredictability and often labour‐related risk.

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Neonatal brachial plexus palsy (NBPP) is a prominent form of newborn morbidity with a potentially disabling persistence. Neurosurgical intervention is indicated in select NBPP patients. Early prognostic assessment would facilitate rational selection of those infants for surgery. We conducted a systematic literature review to determine the prognostic value of early electrodiagnosis (EDx) in NBPP. We included 16 observational studies with a total sample size of 747 children. Risk of bias and quality of evidence were rated. Wide variation was found in EDx techniques, outcome algorithms, and decisionmaking. Nevertheless, the most methodologically sound studies support the use of EDx, at standardized time-frames, as a key prognostic modality for complementing clinical judgment and neuroimaging. An accurate knowledge of the underlying anatomy of the nerve injury helps to counsel families and to guide reconstructive strategy. K E Y W O R D S brachial plexus neuropathy, electrodiagnosis, electrodiagnostic testing, neonatal brachial plexus palsy, prognosis 1 | INTRODUCTION Neonatal brachial plexus palsy (NBPP) is reported to occur in 0.1 to 8.10 per 1000 live births worldwide. 1-6 It is the result of a closed nerve stretch injury to the brachial plexus during the perinatal period. The most common lesions occur within the C5 and C6 spinal nerves (80% of patients), with a smaller group of patients having more extensive lesions, ranging from C5 to C7 and from C5 to T1 (panplexopathy). 7Prevention is difficult due to the unpredictability and multifactorial nature of the risk factors. As severity varies from neurapraxia, axonotmesis, and neurotmesis, to root avulsion, and the extent of injury varies between damage to one nerve or all roots, the impact of neonatal plexopathy ranges from temporary functional impairment to a lifelong total paralysis of one arm. 3,5,[8][9][10][11][12][13][14] Early management includes parental counseling; family support; handling information; splinting; and appropriate, early, and supervised rehabilitation. Neurosurgical intervention is usually undertaken between 3 and 12 months of age in children who have shown little or no significant improvement in the affected muscle groups. 2,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] It is generally agreed that early surgical nerve repair can greatly improve the functional outcome in select patients. 15,20,22,24,[31][32][33] Delay to time of surgery often results in progressive worsening of deformity in the shoulder joint as contractures progress quickly over time in a rapidly growing infant. 34 Surgery in the first months of life is therefore indicated for serious Abbreviations:

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