Risk Factors for Mortality and Neurodevelopmental Impairment among Neonates Born at 22-23 Weeks' Gestation.

INTRODUCTION: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22-23 weeks' gestational age, which currently remain unclear. METHODS: This retrospective case-control study included 104 infants delivered at 22-23 weeks' gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors' follow-up (61/65) was achieved in this study. RESULTS: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks' gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (<5th percentile) was higher (14.7 vs. 1.5%, p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. CONCLUSIONS: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22-23 weeks' gestation. NDI at 36-42 months' chronological age was associated with PVHI.

Qualitative analysis of actual Standard for Exchange of Nonclinical Data (SEND) datasets for Data Domains: Proposition from Japan Pharmaceutical Manufacturers Association SEND Taskforce Team on standardization of nonclinical data.

The Standard for Exchange of Nonclinical Data (SEND) has been adopted by the US FDA, which has required pharmaceutical companies who are developing new drugs for the US market to implement SEND. The Japan Pharmaceutical Manufacturers Association (JPMA) SEND Taskforce Team responded to this situation by starting a project to better understand the contents of SEND datasets. The project focused on domains generally included in the SEND domains for single- and repeat-dose general toxicology studies, and surveyed what kind of information are populated in which domains and in what way. The qualitative analysis of the results indicated that variations exist based on whether or not an individual variable was populated and on how the variable was populated. The Taskforce Team recommends reducing variations not only in the SEND datasets but also in the descriptions in the study protocol and/or final study report. Reduction of such variations should lead to higher quality datasets with powerful and increased searchability so that accumulated SEND datasets should become more valuable. These efforts would provide regulatory agencies with easier review of SEND datasets, which contributes to efficient development of new drug candidates.

Safety, speed, and effectiveness of air transportation for neonates.

BACKGROUND: In Japan, 44.3% of neonates are delivered in private clinics without an attending pediatrician. Obstetricians in the clinics must resuscitate asphyxiated neonates in unstable condition, such as respiratory failure, and they are frequently transferred to tertiary perinatal medical centers. There has been no study comparing the physiological status and prognosis of neonates transported by ambulance with those transported by helicopter. METHODS: Medical and transport records were used to compare the physiological status of neonates transported to Kagoshima City Hospital by land and those transported by air between January 1, 2013, and December 31, 2017. RESULTS: Data from 425 neonates transferred by land and 143 by air were analyzed. There were no significant differences between the two groups in mean gestational age, mean birthweight, fetal blood pH, Apgar score, or the Score for Neonatal Acute Physiology with Perinatal Extension-II (SNAPPE-II) on arrival to the tertiary center (16.3 ± 15.4 [95% confidence interval (CI): 13.2-17.7] vs 16.4 ± 15.4 [95% CI: 13.9-19.0], respectively; P = 0.999); both groups had SNAPPE-II score 10-19, indicating no difference in mortality risk. The times to starting first aid and to admission to the intensive care unit were significantly reduced in neonates transported by air than by land. In subgroup analysis of patients of a gestational age ≤28 weeks, all cases of severe intraventricular hemorrhage (IVH) were observed in the land transportation group. CONCLUSIONS: Neonatal transportation by air is as safe as land transportation, and time to first aid and intensive care are significantly reduced by transportation by air than by land. Air transport could also contribute to the prevention of IVH in neonatal transportation.

Extracorporeal membrane oxygenation in 61 neonates: Single-center experience.

BACKGROUND: There have been few reports on the outcome of extracorporeal membrane oxygenation (ECMO) in newborn Japanese infants. METHODS: A review was carried out of 61 neonates with ECMO between January 1995 and December 2015 at a single center. ECMO was used in neonates with oxygenation index >20 after conventional treatment. Background factors, such as etiology, vascular access mode (veno-venous [VV] or veno-arterial [VA]), number of days with ECMO, and early ECMO (within 24 h after birth), were analyzed in relation to outcome with respect to survival to hospital discharge (SHD). RESULTS: Survival to hospital discharge was achieved in 35 infants (57%), while the remaining 26 died during hospital stay. Gestational age at birth was significantly higher and number of days with ECMO was significantly lower in SHD infants compared with those with adverse outcome (median, 4.0 vs 5.5 days, respectively; P = 0.008). The SHD rate was significantly higher for those with VV than VA vascular access mode (78%, 18/23 vs 45%, 17/38, respectively; P = 0.016), and for those with than without early ECMO (72%, 28/39 vs 32%, 7/22, respectively; P = 0.003). The SHD rate was relatively high in neonates with meconium aspiration syndrome (86%, 12/14), persistent pulmonary hypertension associated with hypoxic ischemic encephalopathy (75%, 6/8), and emphysema (80%, 4/5). On stepwise logistic regression analysis two independent factors of SHD were identified: early ECMO (OR, 9.63; 95%CI: 2.47-37.6) and ECMO length <8 days (OR, 8.05; 95%CI: 1.94-33.5). CONCLUSIONS: Neonates with early ECMO and those with ECMO duration <8 days may benefit from ECMO with respect to SHD.

Atropine-induced inhibition of sperm and semen transport impairs fertility in male rats.

Previous studies revealed that atropine reduced male fertility in rats without any effects on mating performance, sperm production and motility, and testicular morphology. The present study was conducted to investigate whether the impairment of male fertility induced by atropine was related to the inhibition of sperm and semen transports from the vas deferens and seminal vesicle to the urethra during the process of emission. Male rats were treated with atropine at 125 mg/kg/day for 10-17 days prior to mating with untreated females. After confirmation of mating, male rats were euthanized and sperm number in the vas deferens and weights of the seminal vesicle and copulatory plug were determined as indicators of inhibition of sperm and semen transports, respectively. Reproductive status of mated females was determined on gestation days 15-17. A low pregnancy rate associated with a decreased number of implants was observed in females that mated with the atropine-treated males. The average number of sperm in the vas deferens was increased in the atropine-treated males. The average seminal vesicle weight in the atropine-treated males was greater than that of controls. The copulatory plug weights were decreased in the atropine-treated males. These results suggest that inhibitions of sperm and semen transports from the vas deferens and seminal vesicle to the urethra during the process of emission result in reduced male fertility in rats.