Context Daily growth hormone (GH) injections can be burdensome for patients and carers. Somapacitan is a long-acting, reversible albumin-binding GH derivative in development for once-weekly administration in patients with growth hormone deficiency (GHD). Objective The objective of this study is to evaluate the efficacy, safety, and tolerability of once-weekly somapacitan vs once-daily GH. Design REAL 3 is a multicenter, randomized, controlled, double-blind (somapacitan doses), phase 2 study with a 26-week main and 26-week extension phase (NCT02616562). Setting This study took place at 29 sites in 11 countries. Patients Fifty-nine GH treatment-naive prepubertal children with GHD were randomly assigned; 58 completed the trial. Interventions Interventions comprised 3 somapacitan doses (0.04 [n = 16], 0.08 [n = 15], or 0.16 mg/kg/wk [n = 14]) and daily GH (0.034 mg/kg/d [n = 14]), administered subcutaneously. Main Outcome Measures The primary end point was height velocity (HV) at week 26. Secondary efficacy end points included HV SD score (SDS) and insulin-like growth factor-I (IGF-I) SDS. Results At week 26, mean (SD) annualized HV for the somapacitan groups was 8.0 (2.0), 10.9 (1.9), and 12.9 (3.5) cm/year, respectively, vs 11.4 (3.3) cm/year for daily GH; estimated treatment difference (somapacitan 0.16 mg/kg/week—daily GH): 1.7 [95% CI –0.2 to 3.6] cm/year. HV was sustained at week 52, and significantly greater with somapacitan 0.16 mg/kg/week vs daily GH. Mean (SD) change from baseline in HV SDS at week 52 was 4.72 (2.79), 6.14 (3.36), and 8.60 (3.15) for the somapacitan groups, respectively, vs 7.41 (4.08) for daily GH. Model-derived mean (SD) IGF-I SDS for the somapacitan groups was −1.62 (0.86), −1.09 (0.78), and 0.31 (1.06), respectively, vs −0.40 (1.50) observed for daily GH. Safety and tolerability were consistent with the profile of daily GH. Conclusions In children with GHD, once-weekly somapacitan 0.16 mg/kg/week provided the closest efficacy match with similar safety and tolerability to daily GH after 26 and 52 weeks of treatment. A short visual summary of our work is available (1).

BackgroundCongenital adrenal hyperplasia (CAH) cause life-threatening adrenal crisis. It also affects fetal sex development and can result in incorrect sex assignment at birth. In 1989, a newborn screening program for congenital adrenal hyperplasia (CAH) was introduced in Tokyo. Here we present the results of this screening program in order to clarify the efficiency of CAH screening and the incidence of CAH in Japan.MethodFrom 1989 to 2013, a total of 2,105,108 infants were screened for CAH. The cutoff level for diagnosis of CAH was adjusted for gestational age and birth weight.ResultsA total of 410 infants were judged positive, and of these, 106 patients were diagnosed with CAH, indicating a positive predictive value (PPV) of 25.8 %. Of the 106 patients, 94 (88.7 %) were diagnosed with 21-OHD. Of these 94 patients, 73 were diagnosed with the salt wasting form, 14 with the simple virilising form and 7 with the nonclassical form (NC21OHD). The mean birth weight and gestational age were 3192 ± 385 g and 38.9 ± 1.38 weeks. 11 out of 44 female patients were assigned as female according to their screening result.ConclusionsThese data suggest that the newborn screening in Tokyo was effective, especially for sex assignment and preventing fatal adrenal crisis. The incidence of CAH was similar to that measured in previous Japanese screening studies, and it was also similar to that of western countries. The incidence of NC21OHD in Japan in the present study was lower than that in western countries as previous studies reported. The screening program achieved higher PPV than previous CAH screening studies, which might be due to the use of variable cutoffs according to gestational age and birth weight. However, most of the neonates born at 37 weeks or less that were referred to hospital were false-positives. Further changes are needed to reduce the number of false positive preterm neonates.

Abstract.Factors affecting growth and development in extremely low birth weight infants (ELBWIs) born small for gestational age (SGA) have not been precisely elucidated. We performed a retrospective analysis of ELBWIs born SGA who were treated in the neonatal intensive care unit of Kawaguchi Municipal Medical Centre, Japan. A total 244 ELBWIs were born from 2003 to 2010, and 31 were born with weight and height below the 10th percentile for their gestational age. Among the 31 ELBWIs born SGA, we excluded 9 who died before they reached 3 yr of age or who had severe developmental retardation. A total of 16 patients (weight, 510–998 g; GA, 28w0d–32w5d) who were followed until age 3 yr were eligible for our study. At age 3 yr, 94% and 88% of ELBWIs were above the −2 standard deviation (SD) for height and weight, respectively. A history of mechanical ventilation was associated with height. The average score of the full developmental quotient (DQ) was 85, and 63% (10/16) of ELBWIs scored more than 85. Lower Apgar score (≤ 7) was a risk factor for lower DQ scores in motor development and full development. Our study revealed that most ELBWIs born SGA were more than −2 SD below the mean for height and body weight.

Stickler syndrome (STL) is an autosomal, dominantly inherited, clinically variable and genetically heterogeneous connective tissue disorder characterized by ocular, auditory, orofacial and skeletal abnormalities. We conducted targeted resequencing using a next-generation sequencer for molecular diagnosis of a 2-year-old girl who was clinically suspected of having STL with Pierre Robin sequence. We detected a novel heterozygous missense mutation, NM_001854.3:n.4838G>A [NM_001854.3 (COL11A1_v001):c.4520G>A], in COL11A1, resulting in a Gly to Asp substitution at position 1507 [NM_001854.3(COL11A1_i001)] within one of the collagen-like domains of the triple helical region. The same mutation was detected in her 4-year-old brother with cleft palate and high-frequency sensorineural hearing loss.