Seminars in Fetal & Neonatal Medicine RSS feed: Articles in Press. Seminars in Fetal & Neonatal Medicine (formerly Seminars in Neonatology ) is a bi-monthly journal which publishes topic-based issues, including current 'Hot Topics' on the latest advances in fetal and neonatal medicine. The change in title relates to the growing interest amongst obstetricians, midwives and fetal medicine specialists. The Journal commissions review-based content covering current clinical opinion on the care and treatment of the neonate and draws on the necessary specialist knowledge, including that of the respiratory physician, the infectious disease physician, the surgeon, as well as the paediatrician and obstetrician. Each topic-based issue is edited by an authority in their field and contains 8-10 articles. Recent Issues have included: • Newer Concepts in Neonatal Respiratory Care • Perinatal Infection: Detection and Prevention • Multiple Births • Neonatal Jaundice • Inborn Errors of Metabolism Seminars in Fetal & Neonatal Medicine provides: • coverage of major developments in neonatal care; • value to practising neonatologists, consultant and trainee paediatricians, obstetricians, midwives and fetal medicine specialists wishing to extend their knowledge in this field; • up-to-date information in an attractive and relevant format. Book Reviews Seminars in Fetal and Neonatal Medicine accepts relevant books for inclusion in the book review section. Please contact Associate Publisher, Lindsay Campbell, Elsevier, 32 Jamestown Road, London, NW1 7BY; l.campbell@elsevier.com for further information or to submit books for consideration.http://www.sfnmjournal.com//inpress?rss=yesElsevier Inc.en © 2010 Elsevier Ltd. All rights reserved. Seminars in Fetal & Neonatal Medicine1744-165X2010-03-08 © 2010 Elsevier Ltd. All rights reserved. healthpermissions@elsevier.comhttp://www.sfnmjournal.com/article/PIIS1744165X10000132/abstract?rss=yesSummary: Neuroprotection is a major health care priority, given the enormous burden of human suffering and financial cost caused by perinatal brain damage. With the advent of hypothermia as therapy for term hypoxic–ischemic encephalopathy, there is hope for repair and protection of the brain after a profound neonatal insult. However, it is clear from the published clinical trials and animal studies that hypothermia alone will not provide complete protection or stimulate the repair that is necessary for normal neurodevelopmental outcome. This review critically discusses drugs used to treat seizures after hypoxia–ischemia in the neonate with attention to evidence of possible synergies for therapy. In addition, other agents such as xenon, N-acetylcysteine, erythropoietin, melatonin and cannabinoids are discussed as future potential therapeutic agents that might augment protection from hypothermia. Finally, compounds that might damage the developing brain or counteract the neuroprotective effects of hypothermia are discussed.Synergistic neuroprotective therapies with hypothermia - Corrected ProofMaria Roberta Cilio, Donna M. Ferriero10.1016/j.siny.2010.02.002Seminars in Fetal & Neonatal Medicine (2010)2010-03-08Seminars in Fetal & Neonatal Medicine2010-03-08http://www.sfnmjournal.com/article/PIIS1744165X10000144/abstract?rss=yesSummary: Hypothermia is a potential neuroprotective intervention to treat neonatal post-asphyxial (hypoxic–ischemic) encephalopathy (HIE). In this meta-analysis of 13 clinical trials published to date, therapeutic hypothermia was associated with a highly reproducible reduction in the risk of the combined outcome of mortality or moderate-to-severe neurodevelopmental disability in childhood. This improvement was internally consistent, as shown by significant reductions in the individual risk for death, moderate-to-severe neurodevelopmental disability, severe cerebral palsy, cognitive delay, and psychomotor delay. Patients in the hypothermia group had higher incidences of arrhythmia and thrombocytopenia; however, these were not clinically important. This analysis supports the use of hypothermia in reducing the risk of the mortality or moderate-to-severe neurodevelopmental disability in infants with moderate HIE.Hypothermia: a systematic review and meta-analysis of clinical trials - Corrected ProofPrakesh S. Shah10.1016/j.siny.2010.02.003Seminars in Fetal & Neonatal Medicine (2010)2010-03-08Seminars in Fetal & Neonatal Medicine2010-03-08http://www.sfnmjournal.com/article/PIIS1744165X09001231/abstract?rss=yesSummary: Chronic bilirubin encephalopathy (kernicterus) can be diagnosed using semi-objective criteria based on history, physical and neurological examination and laboratory findings including auditory brainstem responses and magnetic resonance imaging. Classical kernicterus is a well-described clinical tetrad of (i) abnormal motor control, movements and muscle tone, (ii) an auditory processing disturbance with or without hearing loss, (iii) oculomotor impairments, especially impairment of upward vertical gaze, and (iv) dysplasia of the enamel of deciduous teeth. Subtle kernicterus or bilirubin-induced neurologic dysfunction (BIND) refers to individuals with subtle neurodevelopmental disabilities without classical findings of kernicterus that, after careful evaluation and consideration, appear to be due to bilirubin neurotoxicity. Kernicterus can be further classified as auditory predominant or motor predominant and characterized based on the severity of clinical sequelae. Proposed research definitions for kernicterus diagnosis in infants from 3 to 18 months are reviewed, as are treatments of auditory and motor deficits and other complications of bilirubin encephalopathy.Chronic bilirubin encephalopathy: diagnosis and outcome - Corrected ProofSteven M. Shapiro10.1016/j.siny.2009.12.004Seminars in Fetal & Neonatal Medicine (2010)2010-01-29Seminars in Fetal & Neonatal Medicine2010-01-29http://www.sfnmjournal.com/article/PIIS1744165X09001206/abstract?rss=yesSummary: Although it is generally believed that preterm infants are at greater risk for the development of bilirubin-associated brain damage than term infants, quantification of the magnitude of this risk has proven elusive, as has a consensus among experts on the level of total serum bilirubin at which therapy should be initiated. Two large randomized studies have been performed that shed some light on the risk hyperbilirubinemia poses for preterm neonates and both studies are reviewed. Additional study is needed to further clarify the risk posed by hyperbilirubinemia in premature neonates and to frame guidelines for phototherapy and exchange transfusion that are more evidence-based.Enduring controversies in the management of hyperbilirubinemia in preterm neonates - Corrected ProofJon F. Watchko, M. Jeffrey Maisels10.1016/j.siny.2009.12.003Seminars in Fetal & Neonatal Medicine (2010)2010-01-11Seminars in Fetal & Neonatal Medicine2010-01-11http://www.sfnmjournal.com/article/PIIS1744165X09001048/abstract?rss=yesSummary: Although kernicterus is a rare condition, it is still being reported in North America and Western Europe in addition to less developed parts of the world. The majority of affected infants are term and late-preterm newborns who have been discharged from the nursery as ‘healthy newborns’ yet have subsequently developed extreme hyperbilirubinemia and the classic neurodevelopmental findings associated with kernicterus. Published guidelines provide the basic tools for preventing hazardous hyperbilirubinemia and the two most important of these are a systematic assessment, prior to discharge, of each infant, for the risk of severe hyperbilirubinemia, and appropriate follow-up based on the time of discharge and the risk assessment. The most recent recommendations call for a predischarge measurement of the serum or transcutaneous bilirubin in all infants. When combined with the gestational age and other risk factors for hyperbilirubinemia, this provides the best estimate of the risk, or lack of risk, for subsequent hyperbilirubinemia, and determines the timing of follow-up and the need for further evaluation and treatment. The application of these principles to the management of the jaundiced newborn might not eliminate every case of kernicterus, but should contribute to a reduction in its occurrence.Screening and early postnatal management strategies to prevent hazardous hyperbilirubinemia in newborns of 35 or more weeks of gestation - Corrected ProofM. Jeffrey Maisels10.1016/j.siny.2009.10.004Seminars in Fetal & Neonatal Medicine (2009)2009-12-25Seminars in Fetal & Neonatal Medicine2009-12-25http://www.sfnmjournal.com/article/PIIS1744165X09001103/abstract?rss=yesSummary: The potential for genetic variation to modulate neonatal hyperbilirubinemia risk is increasingly being recognized. In particular, polymorphisms across three genes involved in bilirubin production and metabolism [glucose-6-phosphate dehydrogenase (G6PD), uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1), and solute carrier organic anion transporter polypeptide 1B1 (SLCO1B1)] may interact with each other and/or environmental contributors to produce significant hyperbilirubinemia. Variant gene co-expression including compound and synergistic heterozygosity enhances hyperbilirubinemia risk, contributing to the etiologic heterogeneity and complex nature of neonatal jaundice.Exploring the genetic architecture of neonatal hyperbilirubinemia - Corrected ProofJon F. Watchko, Zhili Lin10.1016/j.siny.2009.11.003Seminars in Fetal & Neonatal Medicine (2009)2009-12-21Seminars in Fetal & Neonatal Medicine2009-12-21http://www.sfnmjournal.com/article/PIIS1744165X0900119X/abstract?rss=yes Hazardous levels of unconjugated bilirubin in human neonates pose a direct threat of brain damage. Current population-based kernicterus incidence estimates for term neonates in developed countries range from 1:30,000 to 1:100,000; although, higher rates have been reported for 1) preterm neonates and 2) newborns in developing countries where acute bilirubin encephalopathy is a serious endemic problem. Reports of kernicterus in term and late-preterm infants have increased in the United States and elsewhere since the 1980s underscoring the need for intensified research on the pathobiology of bilirubin-induced brain injury and strategies aimed at kernicterus prevention, charges echoed at the “Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: Bench to Bedside” conference sponsored by the National Institutes of Child Health and Human Development, the NIH Office of Rare Diseases, the Centers for Disease Control, the American Academy of Pediatrics, and the March of Dimes. The current Seminars in Fetal and Neonatal Medicine issue on continuing controversies in perinatal jaundice addresses several clinically relevant topics and areas that merit ongoing clinical and basic research. Encompassed in this volume are insightful contributions on bilirubin biochemistry, metalloporphyrins, fatty acid oxidation disorders, an update regarding birth hospitalization screening and early postnatal strategies to prevent hazardous hyperbilirubinemia, and a review of enduring controversies of hyperbilirubinemia management in preterm neonates. A detailed article on the diagnosis and outcome of chronic bilirubin encephalopathy is provided as well as complimentary pieces on i) G6PD deficiency, ii) the genetic architecture of neonatal hyperbilirubinemia and iii) hyperbilirubinemia in African-American newborns. Ernest Beutler, M.D. (photograph) made numerous contributions to our understanding of neonatal hyperbilirubinemia including seminal papers on G6PD deficiency, Gilbert's syndrome, and the importance of non-random X inactivation in the clinical penetrance of G6PD deficiency in female heterozygotes. Accordingly, this volume is dedicated in his memory.Seminars fetal and neonatal medicine “continuing controversies in perinatal jaundice” - Corrected ProofJon F. Watchko10.1016/j.siny.2009.12.002Seminars in Fetal & Neonatal Medicine (2009)2009-12-21Seminars in Fetal & Neonatal Medicine2009-12-21EDITORIALhttp://www.sfnmjournal.com/article/PIIS1744165X09001115/abstract?rss=yesSummary: Neonatal jaundice in the first week of life is a common problem in newborns. It is due to an imbalance of bilirubin production and its elimination, which can lead to significantly elevated levels of circulating bilirubin or hyperbilirubinemia. Use of phototherapy and/or exchange transfusion are the current modes for treating neonatal hyperbilirubinemia and preventing any neurologic damage. These strategies, however, only remove bilirubin that has already been formed. Preventing the production of excess bilirubin may be a more logical approach. Synthetic heme analogs, metalloporphyrins, are competitive inhibitors of heme oxygenase, the rate-limiting enzyme in bilirubin production, and their use has been proposed as an attractive alternative strategy for preventing or treating severe hyperbilirubinemia.Metalloporphyrins in the management of neonatal hyperbilirubinemia - Corrected ProofDavid K. Stevenson, Ronald J. Wong10.1016/j.siny.2009.11.004Seminars in Fetal & Neonatal Medicine (2009)2009-12-14Seminars in Fetal & Neonatal Medicine2009-12-14http://www.sfnmjournal.com/article/PIIS1744165X09001073/abstract?rss=yesSummary: Glucose-6-phosphate dehydrogenase deficiency is a commonly occurring genetic condition, likely to be encountered today in virtually any corner of the globe. Sudden episodes of hemolysis associated with the condition may result in exponential increases in serum total bilirubin concentrations to levels at which bilirubin-induced neurologic damage may occur. The hyperbilirubinemia is the result of complex interactions between genes and environment. Neonatal screening programs coupled with parental and medical caretaker education may be successful in limiting the severity of disease.Glucose-6-phosphate dehydrogenase deficiency and severe neonatal hyperbilirubinemia: a complexity of interactions between genes and environment - Corrected ProofMichael Kaplan, Cathy Hammerman10.1016/j.siny.2009.10.007Seminars in Fetal & Neonatal Medicine (2009)2009-11-30Seminars in Fetal & Neonatal Medicine2009-11-30http://www.sfnmjournal.com/article/PIIS1744165X09001085/abstract?rss=yesSummary: African American neonates evidence a low incidence of hyperbilirubinemia yet account for more than 25% of the reported kernicterus cases in the USA. Glucose-6-phosphate dehydrogenase (G6PD) deficiency accounts for ∼60%, and late preterm gestation and ABO hemolytic disease ∼40% of these cases. Females heterozygous for G6PD A− harbor a population of G6PD-deficient red blood cells and are at risk for hyperbilirubinemia. Pre-discharge bilirubin measurement coupled with gestational age enhances the identification of neonates at hyperbilirubinemia risk. Parental education at the time of birth hospitalization discharge combined with timely follow-up may help to reduce the risk of developing hazardous hyperbilirubinemia.Hyperbilirubinemia in African American neonates: clinical issues and current challenges - Corrected ProofJon F. Watchko10.1016/j.siny.2009.11.001Seminars in Fetal & Neonatal Medicine (2009)2009-11-26Seminars in Fetal & Neonatal Medicine2009-11-26http://www.sfnmjournal.com/article/PIIS1744165X0900105X/abstract?rss=yesSummary: Despite a century of research, several clinically relevant areas of bilirubin biochemistry remain controversial, poorly understood, or unrecognized. These include: (i) The structure and molecularity of bilirubin under physiological environments such as membranes, brain tissue and when bound to proteins. Related to this is the large number of structurally different bilirubin species that may occur in blood under pathological conditions and their potential effects on measurements of bilirubin and free bilirubin. (ii) The mechanism of phototherapy, the neurotoxicity of the photoisomers produced and their influence on measurements of bilirubin and free bilirubin. (iii) The role of membrane transporters in the passage of unconjugated bilirubin across the placenta, intestine, vascular epithelium, blood–brain barrier, and into the liver. (iv) Biochemical mechanisms of bilirubin toxicity, pharmacologic prevention of kernicterus, the contribution of bilirubin to antioxidant defenses, and the practical value of free bilirubin measurements for identifying infants at most risk of kernicterus.Controversies in bilirubin biochemistry and their clinical relevance - Corrected ProofAntony F. McDonagh10.1016/j.siny.2009.10.005Seminars in Fetal & Neonatal Medicine (2009)2009-11-23Seminars in Fetal & Neonatal Medicine2009-11-23http://www.sfnmjournal.com/article/PIIS1744165X09001061/abstract?rss=yesSummary: Mitochondrial fatty acid β-oxidation (FAO) disorders have become an important group of inherited metabolic disorders causing serious pediatric and maternal morbidity and mortality. More than 20 defects affecting β-oxidation have been discovered, characterized by distinct enzyme or transporter deficiencies. This growing number of FAO disorders covers a wide spectrum of phenotypes and are characterized by a wide array of clinical presentations. We discuss the major mitochondrial FAO disorders and the impact they have on maternal health and neonatal outcomes; diagnostic tools and the value of genetic screening are reviewed; and current therapeutic approaches and management strategies are discussed.Fatty acid oxidation disorders: maternal health and neonatal outcomes - Corrected ProofR. Scott Rector, Jamal A. Ibdah10.1016/j.siny.2009.10.006Seminars in Fetal & Neonatal Medicine (2009)2009-11-19Seminars in Fetal & Neonatal Medicine2009-11-19