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Neonatal herpes simplex virus infection

Key points Herpes simplex virus (HSV) is a virus that can cause severe infection in a neonate but also has treatment options that can improve disease outcomes. There are three periods of acquisition of HSV: in utero, perinatal, and postnatal. HSV can be diagnosed via polymerase chain reaction (PCR) of blood and cerebrospinal fluid (CSF), as well as surface cultures and PCR. It is important to…

When and how to treat neonatal CMV infection

Key points Congenital cytomegalovirus (CMV) is the leading infectious cause of hearing loss and neurologic deficits, affecting up to 1% of live births worldwide. Symptomatic congenital CMV infection should be treated with ganciclovir or valganciclovir for 6 months to reduce or ameliorate long-term neurologic deficits, including hearing loss and developmental delay. Studies suggest that some infants with asymptomatic or mild congenital CMV infection at birth may…

Empiric therapy for neonatal sepsis

Key points Most early-onset infections in high-resource settings are caused by group B Streptococcus and Escherichia coli. Ampicillin + gentamicin is an appropriate empirical antibiotic regimen for early-onset sepsis in most settings. Most late-onset infections are caused by Gram-positive organisms. Nafcillin + gentamicin balances the need for a narrow spectrum with the risks of potentially providing inadequate empirical treatment in most cases. Empirical antimicrobials targeting methicillin-resistant…

Management of the asymptomatic newborn at risk for sepsis

Key points The current incidence of neonatal early-onset sepsis (EOS) among infants born ≥37 weeks is relatively low (≈1/2000) and as much as 20-fold lower among well-appearing term infants. There are three major approaches to EOS risk assessment among term infants: categorical consideration of risk factors, multivariate consideration of risk factors in combination with clinical condition, and consideration of the clinical condition alone as it evolves…

Pathophysiologic importance of platelets in neonatal necrotizing enterocolitis

Introduction The onset of necrotizing enterocolitis (NEC) is associated with decreased platelet counts in most patients within 24 hours, and the severity of this thrombocytopenia (defined as platelet counts <150 × 10 9 /L) typically correlates with the severity and extent of intestinal injury. The platelet counts usually continue to drop until 3 days after disease onset. Patients with the most severe, surgical NEC may develop…

Evidence-based guidelines for administering fresh frozen plasma in the NICU

Introduction Fresh frozen plasma (FFP) is the most commonly used hemostatic agent in neonatal intensive care units (NICUs), especially among critically ill neonates and for those who need extracorporeal life support (ECLS). Current guidelines on FFP administration in neonates are mainly based on poor-quality evidence, and therefore a lack of consensus exists on its optimal use. Making the right diagnosis of coagulopathy in neonates and determining…

Novel approaches to identify NICU patients who would benefit from platelet transfusions

Introduction The underlying reasons for bleeding are multifactorial and likely include a combination of hematologic (i.e., platelet, von Willebrand factor [vWF], coagulation factors) and environmental factors such as vessel wall integrity, inflammation, and hemodynamic status. However, it is unknown to what extent these components contribute to bleeding. Since platelets have a major role in primary hemostasis, a low platelet count is considered a risk factor for…

Recent advances in NICU platelet transfusions

Introduction Thrombocytopenia (defined as a platelet count <150 × 10 9 /L) is the second most common hematologic problem among neonates admitted to the neonatal intensive care unit (NICU), affecting 20% to 25% of this patient population. The incidence of thrombocytopenia increases with decreasing gestational age and birth weight, reaching ~70% among extremely low birth weight (ELBW) neonates (born with a weight <1000 g). The incidence…

Neonatal blood banking and transfusion: Current questions and controversies

Introduction Blood component transfusion is critical to modern neonatal medicine to support oxygen delivery, cardiac output, and maintain hemostasis, especially in the context of preventing bleeding or treating the bleeding neonate. Of all admissions to the neonatal intensive care unit (NICU) in the United States, approximately 1.6% receive any blood transfusion, with red blood cell (RBC) transfusion occurring most commonly. Despite the relatively high frequency of…

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.…