Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Experimental studies that are relevant to human pregnancy rely on the selection of appropriate animal models as an important element in experimental design. Consideration of the strengths and weaknesses of any animal model of human disease is fundamental to effective and meaningful translation of preclinical research. Studies in sheep have made significant contributions to our understanding of the normal and abnormal development of the fetus. As a model of human pregnancy, studies in sheep have enabled scientists and clinicians to answer questions about the etiology and treatment of poor maternal, placental, and fetal health and to provide an evidence base for translation of interventions to the clinic. The aim of this review is to highlight the advances in perinatal human medicine that have been achieved following translation of research using the pregnant sheep and fetus.

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual's risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig's potential to enhance clinical therapeutic innovation to improve human health.

Background: Ex-preterm children and adolescents are at risk of developing late-onset neurodevelopmental and behavioral disorders. The mechanisms by which this happens are poorly understood and relevant animal models are required. Methods: Ex-preterm (delivered at 62 d gestation) and term (spontaneously delivered) juvenile guinea pigs underwent behavioral testing at 25 d corrected postnatal age, with tissues collected at 28 d. Neurodevelopmental markers (myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP)) were analyzed in the hippocampus and subcortical white matter by immunohistochemistry. Gamma-aminobutyric acid A (GABA A ) receptor subunit mRNA levels were quantified by reverse transcription polymerase chain reaction (RT-PCR), and salivary cortisol measured by enzyme-linked immunosorbent assay. results: Preterm males travelled greater distances, were mobile for longer, spent more time investigating objects, and approached or interacted with familiar animals more than controls. Myelination and reactive astrocyte coverage was lower in the hippocampus and the subcortical white matter in preterm males. Hippocampal levels of the α5 subunit were also lower in the preterm male brain. Baseline salivary cortisol was higher for preterm males compared to controls. conclusion: We conclude that juvenile ex-preterm male guinea pigs exhibit a hyperactive phenotype and feature impaired neurodevelopment, making this a suitable model for future therapeutic studies. c hildren born preterm (birth at <37 wk gestation) have an increased risk of developing a long-term neurodevelopmental disability (1,2). Importantly, this risk exists even in those thought to be "well" at the time of discharge from neonatal care and in those with no evidence of the structural brain injuries known to be associated with adverse neurodevelopmental outcomes (e.g., intraventricular hemorrhage or periventricular leukomalacia) (3,4). Thus, although intraventricular hemorrhage and, or, periventricular leukomalacia explain neurodevelopmental problems in a subset of high-risk infants, they do not account for the overall burden of neurodisability seen in the ex-preterm population.Although major neurodevelopmental problems are usually picked up early, subtle behavioral or psychiatric disorders may not become apparent until school age, at a time distant from the causative insult (5,6). Anxiety disorder and attention deficit hyperactivity disorder are the most commonly diagnosed disorders in school-aged ex-preterm children (7,8). Attention deficit hyperactivity disorder has a male preponderance and is characterized by a deficit in behavioral inhibition, inattention, impulsivity and social difficulties, whereas anxiety disorder is more commonly diagnosed in ex-preterm females (7,8). Thus, the behavioral outcomes of preterm birth occur in a sex-dependent manner. Other neuropathologies, including depression, and impaired cognitive performance are also increased in those born preterm compared to children and adolescents born at term (5,9-11). Hypo-m...

The cerebellum is derived from the anterior-most segment of the embryonic hindbrain, rhombomere 1 (r1). Previous studies have shown that the early development and patterning of r1 requires fibroblast growth factor (FGF) signaling. However, many of the developmental processes that shape cerebellar morphogenesis take place later in embryonic development and during the first 2 weeks of postnatal life in the mouse. Here, we present a more comprehensive analysis of the expression patterns of genes encoding FGF receptors and secreted FGF ligands during these later stages of cerebellar development. We show that these genes are expressed in multiple cell types in the developing cerebellum, in an astonishing array of distinct patterns. These data suggest that FGF signaling functions throughout cerebellar development to regulate many processes that shape the formation of a functional cerebellum.

The present findings suggest that components of the cerebellar GABAergic system of the ex-preterm cerebellum are disrupted. The higher expression of myelin in the preterm males may be due to a deficit in axonal pruning, whereas females have a deficit in myelination at 28 corrected days of age. Together these ongoing alterations may contribute to the neurodevelopmental and behavioural disorders observed in those born preterm.

Pre-term infants have one of the highest transfusion requirements within the hospital-setting. The vast majority of blood transfusions performed in Neonatal Intensive Care Units (NICUs) are for medically stable pre-term infants with anaemia of prematurity, with the aim of improving oxygen delivery to the vital organs during the crucial phase of growth and development. However, despite the frequency of transfusion in this population, the potential benefits and harms of 'top up' transfusion are not fully understood, leading to practice variation between clinicians, institutions and countries. Significant advances have been made in the prevention of anaemia of prematurity, with recent emphasis on optimising infants' circulatory volume at birth via placental transfusion and preserving infants' own blood volume through innovative minimal sampling techniques. More research is urgently needed to establish optimal transfusion thresholds for these high-risk pre-term infants, for whom benefits as well as adverse outcomes may have consequences that extend for decades throughout the recipients' life-course. In this review, we will discuss some of the consensus and controversies regarding optimal management of anaemia in pre-term infants and highlight potential areas for future research.

Ganaxolone improved neurobehavioural outcomes in males suggesting that neonatal treatment may be an option for reducing preterm-associated neurodevelopmental impairment. However, dosing studies are required to reduce the burden of unwanted side effects.