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Background The aim of this study was to investigate the effect of sex on survival and short-term outcomes of very low-birthweight infants ( VLBWI) born in Japan. Methods This study included VLBWI who were admitted to neonatal intensive care units participating in the Neonatal Research Network of Japan, between 2003 and 2012. The primary outcome was a composite of mortality or any major morbidity, including neurologic injury, bronchopulmonary dysplasia ( BPD), necrotizing enterocolitis ( NEC), or retinopathy of prematurity requiring treatment. Results The composite primary outcome was worse in male infants. Male infants were also more likely to develop BPD. This difference reached statistical significance in neonates born at ≥26 weeks of gestation. In contrast, significant difference in the incidence of NEC was more likely to be seen at 23-25 weeks of gestation. Conclusion Male neonates are more likely to die and are at a higher risk of respiratory and gastrointestinal complications than female neonates. [ABSTRACT FROM AUTHOR]

Background Very low-birthweight (VLBW) infants (VLBWI) are at increased risk for surgical intestinal disorders including necrotizing enterocolitis (NEC), focal intestinal perforation (FIP) and meconium-related ileus (MRI). The aim of this study was to identify disease-specific risk factors for surgical intestinal disorders in VLBWI. Methods A retrospective multicenter case-control study was conducted at 11 institutes. We reviewed VLBWI who underwent laparotomy for intestinal disorders including perforation and intractable bowel obstruction. The surgical disorders were classified into four categories (NEC, FIP, MRI, others) based on the macroscopic findings at operation. In order to identify risk factors, two matched controls for each subject were chosen based on gestational age and birthweight. OR and 95%CI were calculated using a conditional logistic regression model and a multivariate model. Results A total of 150 cases (NEC, n = 44; FIP, n = 47; MRI, n = 42; others, n = 17) and 293 controls were identified. The cases and controls were similar in terms of gestational age and birthweight (cases/controls, 26.7 ± 2.5/26.5 ± 2.6 weeks; 790 ± 256/795 ± 257 g). On multivariate modeling, disease-specific risk factors were as follows: female (OR, 0.23; 95%CI: 0.06-0.89), respiratory distress syndrome (OR, 35.7; 95%CI: 2.48-514) and patent ductus arteriosus (OR, 10.9; 95%CI: 1.51-79.3) for NEC; outborn delivery (OR, 5.47; 95%CI: 1.48-20.2) for FIP; and twin pregnancy (OR, 4.25; 95%CI: 1.06-17.1), PROM (OR, 6.85; 95%CI: 1.33-35.4) and maternal steroid (OR, 0.23; 95%CI: 0.07-0.79) for MRI. Conclusions Different risk factors were identified for NEC, FIP and MRI, suggesting that each disease has a different etiology, and that different strategies are required to prevent these diseases. [ABSTRACT FROM AUTHOR]

Background Surgical intestinal disorders, such as necrotizing enterocolitis ( NEC), focal intestinal perforation ( FIP), and meconium-related ileus ( MRI), are serious morbidities in very low-birthweight infants ( VLBWI). The aim of this study was to compare the composite outcomes of death or neurodevelopmental impairment ( NDI) in VLBWI with surgical intestinal disorders and assess independent risk factors for death and NDI at 18 months of corrected age. Methods A retrospective matched-cohort study was conducted at 11 institutes. We included VLBWI who had undergone laparotomy for NEC, FIP, and MRI. Two control subjects were chosen for every surgical patient and matched for gestational age and birthweight to form the comparison group. Death and neurodevelopmental outcome at 18 months of corrected age were evaluated. Results The number of infants in the NEC, FIP, MRI, and control groups was 44, 47, 42, and 261, respectively. In-hospital mortality was higher in infants with NEC and MRI relative to those in the control group ( P < 0.001). The incidence rate for NDI at 18 months of corrected age was higher in infants with MRI relative to those in the control group ( P = 0.021). On logistic regression analysis, low gestational age, male sex, small for gestational age, intraventricular hemorrhage, and MRI were associated with increased risk of death or NDI at 18 months of corrected age. Conclusions NEC and MRI were associated with in-hospital mortality, and MRI was associated with NDI or death at 18 months of corrected age. [ABSTRACT FROM AUTHOR]

Background This study evaluated the benefit of Bifidobacterium bifidum OLB6378 ( B. bifidum) in very low-birthweight ( VLBW) infants (birthweight <1500 g) for the acceleration of enteral feeding. Methods A cluster-randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals, divided into two groups: the B group ( n = 10 hospitals; B. bifidum given to infants within 48 h of birth) and the P group ( n = 9 hospitals; infants received a placebo). The primary outcome was establishment of enteral feeding after birth, defined as the postnatal day at which enteral feeding exceeded 100 mL/(kg/day). Secondary outcomes were defined as incidence of morbidity and somatic growth before discharge. Results Overall, 283 VLBW infants were enrolled in the study: B group, n = 153; and P group, n = 130. Enteral feeding was established within 21 days after birth in 233 infants, of whom 119 received B. bifidum and 114 received placebo until their bodyweight reached 2000 g. Enteral feeding was established significantly earlier in the B group, at 11.0 ± 3.6 days versus 12.1 ± 3.8days in P group ( P < 0.05). Infant growth during the stay in the neonatal intensive care unit was not different between groups, but the incidence of late-onset sepsis among all enrolled infants was significantly lower in the B group (3.9%, 6/153) than in the P group (10.0%, 13/130; P < 0.05). No differences were observed in the incidence of other adverse outcomes including mortality. Conclusions B. bifidum in VLBW infants accelerated the establishment of enteral feeding after birth without increasing the incidence of adverse effects. [ABSTRACT FROM AUTHOR]

Background Necitumumab (NEC) in combination with gemcitabine+cisplatin (GC) demonstrated significant improvement in overall survival (OS) compared to GC in advanced SqCLC patients (pts) in Global Ph3 study JFCC. In Study JFCM Ph2 part, NEC in combination with GC improved OS compared to GC in SqCLC pts in Japan. Population PK/PD analysis including Study JFCM was conducted to determine the adequacy of the dose in pts in Japan based on NEC PK, and relationship between exposure and efficacy and safety. Methods Two studies, one of which Study JFCM, were added into the analysis previously performed with five Ph 1, 2, and 3 studies. The effect of Japan/non-Japan origin on NEC PK was assessed. Simulations were performed to compare predicted NEC serum concentrations after flat 800 mg and body weight based dosing. The relationship between exposure and OS in Studies JFCC and JFCM Ph2 part was explored. The relationship between exposure and safety measurements (hypomagnesemia, rash and thromboembolic events) in Studies JFCC and JFCM Ph2 part was explored. Results Population PK analysis included blood samples collected from 967 pts (including 114 pts in Japan) treated with NEC. PK parameters were similar between Japanese and non-Japanese pts. NEC PK is dependent on body weight; however, simulations indicated weight-based dosing would not significantly decrease PK variability. Exposure-response analysis included 1195 pts, including 181 pts in Japan. Exposure-efficacy analysis suggested that pts with higher NEC concentration had longer OS, however, majority of pts in both studies had steady state exposure greater than EC80. No correlation was observed between NEC serum exposure and severity of hypomagnesemia or rash. No correlation was observed between NEC serum exposure and risk of treatment emergent thromboembolic events. Conclusion Population PK/PD analysis supports the administration of 800 mg NEC on Day 1 and 8 of a 21-day cycle as an appropriate dose in SqCLC pts in Japan. [ABSTRACT FROM AUTHOR]