Classic spinal muscular atrophy (SMA) is caused by mutations in the telomeric copy of SMN1. Its product is involved in various cellular processes, including cytoplasmic assembly of spliceosomal small nuclear ribonucleoproteins, pre-mRNA processing and activation of transcription. Spinal muscular atrophy with respiratory distress (SMARD) is clinically and genetically distinct from SMA. Here we demonstrate that SMARD type 1 (SMARD1) results from mutations in the gene encoding immunoglobulin micro-binding protein 2 (IGHMBP2; on chromosome 11q13.2-q13.4). In six SMARD1 families, we detected three recessive missense mutations (exons 5, 11 and 12), two nonsense mutations (exons 2 and 5), one frameshift deletion (exon 5) and one splice donor-site mutation (intron 13). Mutations in mouse Ighmbp2 (ref. 14) have been shown to be responsible for spinal muscular atrophy in the neuromuscular degeneration (nmd) mouse, whose phenotype resembles the SMARD1 phenotype. Like the SMN1 product, IGHMBP2 colocalizes with the RNA-processing machinery in both the cytoplasm and the nucleus. Our results show that IGHMBP2 is the second gene found to be defective in spinal muscular atrophy, and indicate that IGHMBP2 and SMN share common functions important for motor neuron maintenance and integrity in mammals.
OBJECTIVE -To investigate the growth of children from pregnancies with gestational diabetes mellitus (GDM) and its association with antenatal maternal, fetal, and recent anthropometric parameters of mother and father. RESEARCH DESIGN AND METHODS -In 324 pregnancies of Caucasian womenwith GDM, BMI before pregnancy, maternal glycemic values, and measurements of the fetal abdominal circumference were recorded. The weight and height of infants were measured at birth and at follow-up at 5.4 years (range 2.5-8.5). In addition, somatic data from routine examinations at 6, 12, and 24 months and the BMI of parents at follow-up were obtained. BMI standard deviation scores (SDSs) were calculated based on age-correspondent data.RESULTS -At all time points, BMI was significantly above average (ϩ0.82 SDS at birth; ϩ0.56 at 6, ϩ0.35 at 12, and ϩ0.32 at 24 months; and ϩ0.66 at follow-up; P Ͻ 0.001). BMI at birth was related to BMI at follow-up (r ϭ 0.27, P Ͻ 0.001). The rate of overweight at follow-up was 37% in children with birth BMI Ն90th percentile and 25% in those with normal BMI at birth (P Ͻ 0.05). Abdominal circumference of third trimester and postprandial glucose values were related to BMI at follow-up (r ϭ 0.22 and r ϭ 0.18, P Ͻ 0.01). Recent maternal, paternal, and birth BMI were independent predictors of BMI at follow-up (r ϭ 0.42, P Ͻ 0.001). Sixty-nine percent of children of parents with BMI Ն30 kg/m 2 were overweight at follow-up compared with 20% of those with parental BMI Ͻ30 kg/m 2 (P Ͻ 0.001).CONCLUSIONS -Children of mothers with GDM have a high rate of overweight that is associated both with intrauterine growth and parental obesity. Diabetes Care 28:1745-1750, 2005G estational diabetes mellitus (GDM) reflects a metabolically altered fetal environment due to an increased maternal supply of carbohydrates leading to fetal hyperinsulinism. Stimulation of the insulin-sensitive tissue results in increased fetal growth, predominantly of the abdomen, and delivery of large-forgestational-age newborns. Clinical and experimental studies have shown that the implications of fetal hyperinsulinism reach far beyond delivery. Children of mothers with diabetes in pregnancy may develop an increased disposition for obesity and glucose intolerance through a nongenetic "fuel-mediated" mechanism (1-8).Disposition for obesity could be influenced by many factors other than maternal diabetes in pregnancy. To our knowledge, there are no studies that evaluate the contribution of maternal hyperglycemia to childhood overweight in comparison to other antepartum maternal and fetal confounders and the influence of the postnatal environment. The present large longitudinal study of infants of mothers treated for GDM aimed to evaluate the association of the level of maternal hyperglycemia during pregnancy, fetal (as assessed by ultrasound) and neonatal obesity, and childhood obesity, as well as maternal and paternal obesity in pregnancies complicated by GDM.RESEARCH DESIGN AND METHODS -The study cohort was recruited from children of mothers wh...
Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.
IMPORTANCE Red blood cell transfusions are commonly administered to infants weighing less than 1000 g at birth. Evidence-based transfusion thresholds have not been established. Previous studies have suggested higher rates of cognitive impairment with restrictive transfusion thresholds.OBJECTIVE To compare the effect of liberal vs restrictive red blood cell transfusion strategies on death or disability. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted in 36 level III/IV neonatal intensive care units in Europe among 1013 infants with birth weights of 400 g to 999 g at less than 72 hours after birth; enrollment took place between July 14, 2011, and November 14, 2014, and follow-up was completed by January 15, 2018.INTERVENTIONS Infants were randomly assigned to liberal (n = 492) or restrictive (n = 521) red blood cell transfusion thresholds based on infants' postnatal age and current health state. MAIN OUTCOME AND MEASURESThe primary outcome, measured at 24 months of corrected age, was death or disability, defined as any of cognitive deficit, cerebral palsy, or severe visual or hearing impairment. Secondary outcome measures included individual components of the primary outcome, complications of prematurity, and growth. RESULTS Among 1013 patients who were randomized (median gestational age at birth, 26.3 [interquartile range {IQR}, 24.9-27.6] weeks; 509 [50.2%] females), 928 (91.6%) completed the trial. Among infants in the liberal vs restrictive transfusion thresholds groups, respectively, incidence of any transfusion was 400/492 (81.3%) vs 315/521 (60.5%); median volume transfused was 40 mL (IQR,16-73mL)vs19mL(IQR,0-46mL);andweeklymeanhematocritwas3percentagepointshigher withliberalthresholds.Theprimaryoutcomewasnotsignificantlydifferentbetweengroups,norwere the secondary outcomes of death, cognitive deficit, or cerebral palsy. In the liberal vs restrictive thresholds groups, respectively, necrotizing enterocolitis requiring surgical intervention occurred in 20/492 (4.1%) vs 28/518 (5.4%); bronchopulmonary dysplasia occurred in 130/458 (28.4%) vs 126/ 485 (26.0%); and treatment for retinopathy of prematurity was required in 41/472 (8.7%) vs 38/492 (7.7%). Growth at follow-up was also not significantly different between groups. Outcomes No./total (%) Absolute difference, % (95% CI) Odds ratio (95% CI) P value Liberal threshold Restrictive threshold Death or neurodevelopmental impairment by 24 mo 200/450 (44.4) 205/478 (42.9) 1.6 (−4.8 to 7.9) 1.05 (0.80-1.39) .72 Death by 24 mo 38/460 (8.3) 44/491 (9.0) −0.7 (−4.3 to 2.9) 0.91 (0.58-1.45) .70 Cognitive deficit 154/410 (37.6) 148/430 (34.4) 3.1 (−3.3 to 9.6) 1.12 (0.83-1.51) .47 Cerebral palsy 18/419 (4.3) 25/443 (5.6) −1.3 (−4.2 to 1.5) 0.75 (0.40-1.40) .37CONCLUSIONS AND RELEVANCE Among infants with birth weights of less than 1000 g, a strategy of liberal blood transfusions compared with restrictive transfusions did not reduce the likelihood of death or disability at 24 months of corrected age.
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