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NICU transfusion guidelines and strategies to minimize transfusions

Introduction Pathologic anemia is defined by a red blood cell (RBC) mass inadequate to meet the oxygen needs of tissues. Neonates often require red cell transfusions due to a decreased red cell mass brought about by acute blood loss. Preterm infants frequently experience a decline in red cell mass due to phlebotomy, a shortened red cell lifespan, and lack of erythropoietic response to a dropping hematocrit…

Erythropoietin and darbepoetin use in the NICU

Introduction Premature infants receive a greater number of transfusions and are exposed to a greater number of donors compared to any other hospitalized population. Transfusion guidelines are now used in many neonatal units; however, the search for the most appropriate transfusion guidelines continues. Recently, two of the largest randomized controlled trials (RCTs) to date enrolled over 2800 extremely low birth weight (ELBW) infants and showed similar…

Using targeted genetic panels to find the causes of neonatal hemolytic anemia

Definition, etiologies, and implications of neonatal hemolytic anemia Neonatal hemolytic anemias (NHA) are a group of pathologic conditions manifesting with low hemoglobin (Hb) levels and/or red blood cell (RBC) counts due to premature destruction of erythrocytes during the perinatal period. These RBCs may be destroyed in the intravascular or the extravascular compartments. Generally, hemolysis is evidenced by anemia and hyperbilirubinemia in this period. RBCs are known…

Risk factors for iron deficiency in neonates

Introduction Iron, although critically necessary, is both a good and a bad actor because excess unbound iron may be toxic. The physiologic window between the extremes of iron deficiency (ID) and excess is narrow. Official guidelines for identifying and managing iron status in ill neonates are based on limited research data and thus are nonspecific and incomplete, especially with parenteral iron administration. Eighty percent of placental-fetal…

Neonatal iron homeostasis

Introduction Iron is critical for various tissues throughout the body, including red blood cells and the brain. While iron can be stored, it cannot be synthesized de novo in the body and therefore is an essential micronutrient that must be provided in the diet. An important feature of iron is that it is not actively excreted from the body, so regulation of total body iron occurs…

New erythrocyte diagnostic parameters in neonatal medicine

Introduction In 1929 Wintrobe published a method for measuring the percent of blood comprised of red cells—the hematocrit. Soon thereafter he reported a method for measuring the volume of the average circulating red blood cell (RBC), in femtoliters (fL, 10 -15 L), as a way to judge whether a patient’s RBCs are normal size or smaller or larger than normal. In that publication Wintrobe also reported…

Age-appropriate biology of neonatal neutrophils

Introduction Unraveling the complexities of intrinsic mechanisms behind the normal transition of the suppressed in utero neutrophil into the fully operational postpartum cell has been a goal of neutrophil biologists for nearly a century. Even though neonatal neutrophils have been historically described as functionally deficient when compared with adult cells, these phenotypic and functional disparities have been evolutionarily perfected over centuries and are essential to the…

Nucleated red blood cells in neonatal medicine

Introduction It is distinctly uncommon and definitely pathologic to have nucleated red blood cells (NRBCs) in the circulating blood. This statement is true for all humans—in fact, for all mammals—with the singular exception of newborn infants, where small numbers of NRBCs can be a normal finding on the day of birth and perhaps for a day or two thereafter. However, some human newborn infants, particularly those…

The pivotal role of macrophages in the pathogenesis of necrotizing enterocolitis

Introduction: Necrotizing enterocolitis Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis seen in infants who are either born extremely premature or are critically ill with multiple organ dysfunction syndrome (MODS). The intestinal injury in NEC begins in the mucosa and progresses outwards, and in severe cases, may result in transmural necrosis and perforation. , Unfortunately, despite major progress in most outcomes, this disease continues to be…

Innovations in screening and management of neonatal hyperbilirubinemia

Introduction One of the most significant innovations in the routine management of neonatal hyperbilirubinemia was the publication of the 2004 clinical practice guidelines on the management of hyperbilirubinemia in late preterm and term newborns by the American Academy of Pediatrics (AAP) Subcommittee on Hyperbilirubinemia. These guidelines were largely based on the innovative method of using predischarge total serum bilirubin (TSB) for hour-specific risk stratification developed by…

Self-Assessment

Chapter 1 Question 1 Why are we concerned with terminology? All research groups know what the words and terms they use mean. Answer 1 It is possible that different research laboratories are finding the same transcription factors or extracellular matrix molecules and giving them different names. It is known that families of enzymes have in the past been renamed or renumbered when this has been identified.…

Neonatal Management and Outcome in Extreme Prematurity

Key Points Improvement in neonatal management over the past decades has led to an increase in survival rates among extreme preterm neonates and a simultaneous decrease in the limits of viability. Despite improvement in perinatal survival, the rates of short- and long-term morbidity (including neurodevelopmental outcome) remain substantial. Optimising transition in the first minutes after birth by improving lung aeration and applying strategies to delay cord…

Pharmacokinetics and Pharmacodynamics

Key Points Physiological changes associated with pregnancy have a profound effect on how medications are handled in pregnant women. Most medications taken by pregnant women reach the fetus to varying degrees. The fetus is in part protected by placental efflux transporters and placental drug-metabolising enzymes. The fetus can also metabolise some drugs but to a minor degree. Drugs reaching the fetus can be teratogenic or toxic,…

The Developmental Origins of Health and Disease

Key Points Influences during early life have substantial impact upon adult health and disease. This concept is most commonly known as the developmental origins of health and disease. Environmental, genetic and epigenetic factors, as well as interactions among these factors, underlie this association. Modification of these factors in early development has the potential to influence an individual’s health across the life course. Introduction An association between…

Fetal Gene Therapy

Key Points Gene therapy for fetuses may provide a therapeutic advantage over postnatal treatment for certain congenital diseases. Three types of fetal gene therapy are available: direct ‘somatic’ fetal gene therapy, in utero transplantation of gene corrected fetal stem cells and maternal gene therapy In preclinical animal models of congenital disease, direct fetal gene therapy can bring a phenotypic cure. Minimally invasive ultrasound-guided injection techniques can…

In Utero Stem Cell Transplantation

Key Points In utero transplantation (IUT) has the potential to cure or ameliorate many disorders before birth. Animal models for studying IUT have fundamental differences from human models in regard to immunologic ontogeny and placentation. Naturally occurring events during pregnancy result in chimerism in large animals and in humans and support the concept of IUT. Using mesenchymal stem cells for IUT may be possible in disorders…

Multiple Pregnancy

Key Points Multiple pregnancies are at high risk for adverse perinatal outcome. The standard of care is early confirmation of chorionicity and timely referral when complications arise. Current available data report similar pregnancy-loss rates in twins for both chorionic villous sampling and amniocentesis with an excess risk for about 1% above the background risk. Selective intrauterine growth restriction or discordant growth complicates approximately 20% of twins.…

Disorders of Amniotic Fluid

Key Points Amniotic fluid (AF) volume is usually well regulated in pregnancy. Subjective or semiquantitative ultrasound measurement systems are used to identify and categorise disorders of AF volume. Low (oligohydramnios) or high (polyhydramnios) AF volumes are associated with increased maternal and perinatal complications. Obstetric management is based on the underlying cause of the abnormal AF volume. Introduction The fetus exists in a fluid-filled environment which assists…

Fetal Infections

Key Points Cytomegalovirus (CMV) can cause both primary and nonprimary infections. Around 50% of the pregnant women are seronegative; 1% will develop primary infection during pregnancy. Prenatal diagnosis relies on CMV polymerase chain reaction (PCR) in amniotic fluid (AF) sampled at least 6 weeks after maternal seroconversion and after 21 weeks. Cerebral fetal lesions determine the prognosis. A total of 10% of infected infants are symptomatic…

Fetal Platelet Disorders

Key Points Fetal platelet disorder is a potentially life-threatening condition. Fetal thrombocytopenia may lead to fetal bleeding. complications, such as an intracranial haemorrhage. Idiopathic thrombocytopenic purpura. Has an incidence of 1 to 2 in 1000 pregnancies. Causes severe fetal thrombocytopenia in 5% to 20% of the cases. Rarely leads to bleeding problems in fetuses or neonates. Is treated primarily with corticosteroids. Fetal and neonatal alloimmune thrombocytopenia.…