The impact of a register on the management of neonatal cooling in Switzerland.

BACKGROUND: Therapeutic hypothermia following hypoxic ischaemic encephalopathy in term infants was introduced into Switzerland in 2005. Initial documentation of perinatal and resuscitation details was poor and neuromonitoring insufficient. In 2011, a National Asphyxia and Cooling Register was introduced. AIMS: To compare management of cooled infants before and after introduction of the register concerning documentation, neuromonitoring, cooling methods and evaluation of temperature variability between cooling methods. STUDY DESIGN: Data of cooled infants before the register was in place (first time period: 2005-2010) and afterwards (second time period: 2011-2012) was collected with a case report form. RESULTS: 150 infants were cooled during the first time period and 97 during the second time period. Most infants were cooled passively or passively with gel packs during both time periods (82% in 2005-2010 vs 70% in 2011-2012), however more infants were cooled actively during the second time period (18% versus 30%). Overall there was a significant reduction in temperature variability (p < 0.001) comparing the two time periods. A significantly higher proportion of temperature measurements within target temperature range (72% versus 77%, p < 0.001), fewer temperature measurements above (24% versus 7%, p < 0.001) and more temperatures below target range (4% versus 16%, p < 0.001) were recorded during the second time period. Neuromonitoring improved after introduction of the cooling register. CONCLUSION: Management of infants with HIE improved since introducing the register. Temperature variability was reduced, more temperature measurements in the target range and fewer temperature measurements above target range were observed. Neuromonitoring has improved, however imaging should be performed more often.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Prenatal Risk Factors and Outcomes in Gastroschisis: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: Gastroschisis is a congenital anomaly with increasing incidence, easy prenatal diagnosis and extremely variable postnatal outcomes. Our objective was to systematically review the evidence regarding the association between prenatal ultrasound signs (intraabdominal bowel dilatation [IABD], extraabdominal bowel dilatation, gastric dilatation [GD], bowel wall thickness, polyhydramnios, and small for gestational age) and perinatal outcomes in gastroschisis (bowel atresia, intra uterine death, neonatal death, time to full enteral feeding, length of total parenteral nutrition and length of in hospital stay). METHODS: Medline, Embase, and Cochrane databases were searched electronically. Studies exploring the association between antenatal ultrasound signs and outcomes in gastroschisis were considered suitable for inclusion. Two reviewers independently extracted relevant data regarding study characteristics and pregnancy outcome. All meta-analyses were computed using individual data random-effect logistic regression, with single study as the cluster unit. RESULTS: Twenty-six studies, including 2023 fetuses, were included. We found significant positive associations between IABD and bowel atresia (odds ratio [OR]: 5.48, 95% confidence interval [CI] 3.1-9.8), polyhydramnios and bowel atresia (OR: 3.76, 95% CI 1.7-8.3), and GD and neonatal death (OR: 5.58, 95% CI 1.3-24.1). No other ultrasound sign was significantly related to any other outcome. CONCLUSIONS: IABD, polyhydramnios, and GD can be used to an extent to identify a subgroup of neonates with a prenatal diagnosis of gastroschisis at higher risk to develop postnatal complications. Data are still inconclusive on the predictive ability of several signs combined, and large prospective studies are needed to improve the quality of prenatal counseling and the neonatal care for this condition.

Impact of Early-Life Exposures on Immune Maturation and Susceptibility to Disease.

Exiting from the largely sterile environment of the womb, the neonatal immune system is not fully mature, and thus neonatal immune cells must simultaneously mount responses against environmental stimuli while maturing. This dynamic process of immune maturation is driven by a variety of cell-intrinsic and extrinsic factors. Recent studies have focused on some of these factors and have shed light on the mechanisms by which they drive immune maturation. We review the interactions and consequences of immune maturation during the pre- and perinatal period. We discuss environmental signals in early life that are needed for healthy immune homeostasis, and highlight detrimental factors that can set an individual on a path towards disease. This early-life period of immune maturation could hold the key to strategies for setting individuals on trajectories towards health and reduced disease susceptibility.

Early childhood constraint therapy for sensory/motor impairment in cerebral palsy: a randomised clinical trial protocol.

INTRODUCTION: Cerebral palsy (CP) is the most common physical disability in childhood. It is a disorder resulting from sensory and motor impairments due to perinatal brain injury, with lifetime consequences that range from poor adaptive and social function to communication and emotional disturbances. Infants with CP have a fundamental disadvantage in recovering motor function: they do not receive accurate sensory feedback from their movements, leading to developmental disregard. Constraint-induced movement therapy (CIMT) is one of the few effective neurorehabilitative strategies shown to improve upper extremity motor function in adults and older children with CP, potentially overcoming developmental disregard. METHODS AND ANALYSIS: This study is a randomised controlled trial of children 12-24 months corrected age studying the effectiveness of CIMT combined with motor and sensory-motor interventions. The study population will comprise 72 children with CP and 144 typically developing children for a total of N=216 children. All children with CP, regardless of group allocation will continue with their standard of care occupational and physical therapy throughout the study. The research material collected will be in the form of data from high-density array event-related potential scan, standardised assessment scores and motion analysis scores. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board. The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: NCT02567630.

Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury.

Perinatal asphyxia induces neuronal cell death and brain injury, and is often associated with irreversible neurological deficits in children. There is an urgent need to elucidate the neuronal death mechanisms occurring after neonatal hypoxia-ischemia (HI). We here investigated the selective neuronal deletion of the Atg7 (autophagy related 7) gene on neuronal cell death and brain injury in a mouse model of severe neonatal hypoxia-ischemia. Neuronal deletion of Atg7 prevented HI-induced autophagy, resulted in 42% decrease of tissue loss compared to wild-type mice after the insult, and reduced cell death in multiple brain regions, including apoptosis, as shown by decreased caspase-dependent and -independent cell death. Moreover, we investigated the lentiform nucleus of human newborns who died after severe perinatal asphyxia and found increased neuronal autophagy after severe hypoxic-ischemic encephalopathy compared to control uninjured brains, as indicated by the numbers of MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3)-, LAMP1 (lysosomal-associated membrane protein 1)-, and CTSD (cathepsin D)-positive cells. These findings reveal that selective neuronal deletion of Atg7 is strongly protective against neuronal death and overall brain injury occurring after HI and suggest that inhibition of HI-enhanced autophagy should be considered as a potential therapeutic target for the treatment of human newborns developing severe hypoxic-ischemic encephalopathy.