"STEP", an early developmental screening tool that predicts one-year outcomes

Certain perinatal complications, such as moderate-to-severe hypoxic–ischemic encephalopathy (HIE) and extreme prematurity (EP), are associated with a more than 50-fold increase in the risk of cerebral palsy, as compared to the risk among infants born at term without complications. EP is associated also with a less severe form of motor impairment, developmental coordination disorder, and with an increased risk of cognitive and related impairments

Families' perspectives on monitoring infants' health and development after discharge from NICUs

Based on a survey of families of very preterm infants, Seppanen et al. report that: (1) parents rated post-discharge (post-NICU) care as poor or fair for 14.2% of children; (2) parents of one-third of children with health or developmental disorders rated their child's post-hospital care as poor or fair, as compared to 12-13% of parents of typically developing and healthy children; and (3) parents' suggestions for ways to improve post-hospital care focused primarily on better communication between the health care team and parents and better coordination of the child's care. These findings point to a large opportunity for improving post-NICU services for infants born very preterm, especially for children with health or developmental disorders. In addition to gathering more information about families' perspectives, vigorous quality improvement methods should be applied to improve the effectiveness of post-NICU clinics and the health and development outcomes of the infants and families served by these clinics

Changes in Self-reported Quality of Life as Survivors of Extremely Preterm Birth Enter Adulthood

Advances in perinatal care of mothers and newborn infants have led to large increases in survival after extremely preterm birth. Currently, with proactive perinatal care, almost one-third of infants born at 22 weeks of gestation survive. Interest continues to grow in longterm outcomes among survivors of extreme prematurity. Extreme prematurity is associated with high rates of perinatal brain injury, chronic lung disease, retinopathy, and systemic infections and contributes disproportionately to the burden of neurodevelopmental impairments, such as cognitive impairment and accompanying functional impairments. Specific impairments have been the focus of most longitudinal research on outcomes after extreme prematurity. An alternative and complementary approach is evaluation of more global outcomes as subjectively assessed by study participants (and their proxy reporters). One such outcome, health-related quality of life (HRQL), was the focus of a study reported in this volume of The Journal by Ni et al

Mediators of attention-deficit/hyperactivity disorder risk in individuals born preterm

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder among children born preterm, with the highest risk group being those born extremely preterm (birth before 28 weeks of gestation). In a large cohort of individuals born extremely preterm, ADHD was the most common psychiatric outcome at 15 years of age with a prevalence of 18%. As compared to individuals born at term, those born most extremely preterm (22–25 weeks of gestation) have a more than fourfold increase in odds of any ADHD diagnosis, with tenfold increase in odds of ADHD inattentive subtype. Identification of pre-, peri-, and postnatal risk factors for ADHD and a better understanding of the mechanisms linking preterm birth and ADHD later in life can inform the identification of ADHD to allow for early intervention, towards the goal of improving the life course of individuals born preterm. A better understanding of risk factors may also allow for interventions to modify or reduce the risk of ADHD among offspring of high-risk pregnancies

Extreme prematurity: Risk and resiliency

Individuals born extremely preterm (before 28 weeks of gestation) comprise only about 0.7% of births in the United States and an even lower proportion in other high resource countries. However, these individuals account for a disproportionate number of children with cerebral palsy, intellectual deficit, autism spectrum disorder, attention deficit hyperactivity disorder, and epilepsy. This review describes two large multiple center cohorts comprised of individuals born extremely preterm: the EPICURE cohort, recruited 1995 in the United Kingdom and the Republic of Ireland, and the Extremely Low Gestational Age Newborn (ELGAN), recruited 2002-2004 in five states in the United States. The primary focus of these studies has been neurodevelopmental disorders, but also of interest are growth, respiratory illness, and parent- and self-reported global health and well-being. Both of these studies indicate that among individuals born extremely preterm the risks of most neurodevelopmental disorders are increased. Early life factors that contribute to this risk include perinatal brain damage, some of which can be identified using neonatal head ultrasound, bronchopulmonary dysplasia, and neonatal systemic inflammation. Prenatal factors, particularly the family's socioeconomic position, also appear to contribute to risk. For most adverse outcomes, the risk is higher in males. Young adults born extremely preterm who have neurodevelopmental impairment, as compared to those without such impairment, rate their quality of life lower. However, young adults born extremely preterm who do not have neurodevelopmental impairments rate their quality of life as being similar to that of young adults born at term. Finally, we summarize the current state of interventions designed to improve the life course of extremely premature infants, with particular focus on efforts to prevent premature birth and on postnatal efforts to prevent adverse neurodevelopmental outcomes

Forming a Primordial Star in a Relic HII Region

There has been considerable theoretical debate over whether photoionization and supernova feedback from the first Population III stars facilitate or suppress the formation of the next generation of stars. We present results from an Eulerian adaptive mesh refinement simulation demonstrating the formation of a primordial star within a region ionized by an earlier nearby star. Despite the higher temperatures of the ionized gas and its flow out of the dark matter potential wells, this second star formed within 23 million years of its neighbor's death. The enhanced electron fraction within the HII region catalyzes rapid molecular hydrogen formation that leads to faster cooling in the subsequent star forming halos than in the first halos. This "second generation" primordial protostar has a much lower accretion rate because, unlike the first protostar, it forms in a rotationally supported disk of approx. 10-100 solar masses. This is primarily due to the much higher angular momentum of the halo in which the second star forms. In contrast to previously published scenarios, such configurations may allow binaries or multiple systems of lower mass stars to form. These first high resolution calculations offer insight into the impact of feedback upon subsequent populations of stars and clearly demonstrate how primordial chemistry promotes the formation of subsequent generations of stars even in the presence of the entropy injected by the first stars into the IGM.Comment: 4 pages, 2 figures. Some revisions, including enhanced discussion of angular momentum issues. Asrophysical Journal, accepte

Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes

Among individuals born very preterm, perinatal inflammation, particularly if sustained or recurring, is highly likely to contribute to adverse neurodevelopmental outcomes, including cerebral white matter damage, cerebral palsy, cognitive impairment, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Antecedents and correlates of perinatal inflammation include socioeconomic disadvantage, maternal obesity, maternal infections, fetal growth restriction, neonatal sepsis, necrotizing enterocolitis, and prolonged mechanical ventilation. Genetic factors can modify susceptibility to perinatal inflammation and to neurodevelopmental disorders. Preliminary evidence supports a role of epigenetic markers as potential mediators of the presumed effects of preterm birth and/or its consequences on neurodevelopment later in life. Further study is needed of factors such as sex, psychosocial stressors, and environmental exposures that could modify the relationship of early life inflammation to later neurodevelopmental impairments. Also needed are pharmacological and non-pharmacological interventions to attenuate inflammation towards the goal of improving the neurodevelopment of individuals born very preterm

Magnetic Resonance Biomarkers in Very Preterm Infants: Relationships to Perinatal Factors

In this volume of The Journal of Pediatrics, Parikh et al report on white matter changes in the brains of a large cohort of very preterm infants (<32 weeks of gestation) who underwent magnetic resonance imaging (MRI) at term equivalent age (39-45 weeks’ postmenstrual age). This research team has developed a method for objectively quantifying the MRI finding of diffuse excessive high signal intensity (DEHSI), and analyzed this measure, which they now refer to as diffuse white matter abnormality (DWMA), in relation to multiple perinatal factors. Factors found to be associated with increased DWMA were pneumothorax, severe bronchopulmonary dysplasia, severe retinopathy of prematurity, and male sex; associated with decreased DWMA were postnatal treatment with dexamethasone, duration of treatment with caffeine, and exclusive human milk diet at discharge. If some of these associations are valid and indicative of causal relationships, and if the putative association between DWMA and neurodevelopmental outcome is valid and causal, the study by Parikh et al could have important implications for clinical care of very preterm infants

Accelerated Aging and the Life Course of Individuals Born Preterm

Individuals born preterm have shorter lifespans and elevated rates of chronic illness that contribute to mortality risk when compared to individuals born at term. Emerging evidence suggests that individuals born preterm or of low birthweight also exhibit physiologic and cellular biomarkers of accelerated aging. It is unclear whether, and to what extent, accelerated aging contributes to a higher risk of chronic illness and mortality among individuals born preterm. Here, we review accelerated aging phenotypes in adults born preterm and biological pathways that appear to contribute to accelerated aging. We highlight biomarkers of accelerated aging and various resiliency factors, including both pharmacologic and non-pharmacologic factors, that might buffer the propensity for accelerated aging among individuals born preterm

Genome-Wide Characterization of the Phosphate Starvation Response in Schizosaccharomyces pombe

Background: Inorganic phosphate is an essential nutrient required by organisms for growth. During phosphate starvation, Saccharomyces cerevisiae activates the phosphate signal transduction (PHO) pathway, leading to expression of the secreted acid phosphatase, PHO5. The fission yeast, Schizosaccharomyces pombe, regulates expression of the ScPHO5 homolog (pho1+) via a non-orthologous PHO pathway involving genetically identified positive (pho7+) and negative (csk1+) regulators. The genes induced by phosphate limitation and the molecular mechanism by which pho7+ and csk1+ function are unknown. Here we use a combination of molecular biology, expression microarrays, and chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to characterize the role of pho7+ and csk1+ in the PHO response. Results: We define the set of genes that comprise the initial response to phosphate starvation in S. pombe. We identify a conserved PHO response that contains the ScPHO5 (pho1+), ScPHO84 (SPBC8E4.01c), and ScGIT1 (SPBC1271.09) orthologs. We identify members of the Pho7 regulon and characterize Pho7 binding in response to phosphate-limitation and Csk1 activity. We demonstrate that activation of pho1+ requires Pho7 binding to a UAS in the pho1+ promoter and that Csk1 repression does not regulate Pho7 enrichment. Further, we find that Pho7-dependent activation is not limited to phosphate-starvation, as additional environmental stress response pathways require pho7+ for maximal induction. Conclusions: We provide a global analysis of the transcriptional response to phosphate limitation in S. pombe. Our results elucidate the conserved core regulon induced in response to phosphate starvation in this ascomycete distantly related to S. cerevisiae and provide a better understanding of flexibility in environmental stress response networks.Chemistry and Chemical BiologyMolecular and Cellular Biolog