Pediatrics_Nelson

Pediatrics_Nelson. Three zones of optical densities with decreasing slopes toward term gestation have been developed to predict the severity of the illness. The high optical density zone 3 is associated with severe hemolysis. Fetuses in the lower zones probably are not affected. If a fetus’s optical density measurement for bilirubin falls into zone 3, and the fetus has pulmonary maturity as determined by the lecithin-to-sphingomyelin ratio, the infant should be delivered and treated in the neonatal intensive care unit. If the lungs are immature and the fetus is between 22 and 33 weeks of gestational age, an ultrasound-guided intrauterine transfusion with O-negative blood into the umbilical vein is indicated and may have to be repeated until pulmonary maturity is reached or fetal distress is detected. Indications for fetal intravascular transfusion in sensitized fetuses between 22 and 32 weeks of gestational age include a fetal hematocrit of less than 25% to 30%, fetal hydrops, and fetal distress too


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Pediatrics_Nelson. for fetal intravascular transfusion in sensitized fetuses between 22 and 32 weeks of gestational age include a fetal hematocrit of less than 25% to 30%, fetal hydrops, and fetal distress too early in gestation for delivery. Intravascular intrauterine transfusion corrects fetal anemia, improves the outcome of severe hydrops, and reduces the need for postnatal exchange transfusion, but is associated with neonatal anemia as a result of continued hemolysis plus suppressed erythropoiesis.


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Pediatrics_Nelson. Prevention of sensitization of the mother carrying an Rh-positive fetus is possible by treating the mother during gestation (>28 weeks’ gestational age) and within 72 hours after birth with anti-Rh-positive immune globulin (RhoGAM). The dose of RhoGAM (300 μg) is based on the ability of this amount of anti-Rh-positive antibody to bind all the possible fetal Rh-positive erythrocytes entering the maternal circulation during the fetal-to-maternal transfusion at birth (approximately 30 mL). RhoGAM may bind Rh-positive fetal erythrocytes or interfere with maternal anti-Rh-positive antibody production by another, unknown mechanism. RhoGAM is effective only in preventing sensitization to the D antigen. Other blood group antigens that can cause immune hydrops and erythroblastosis include Rh C, E, Kell, and Duffy. Anti-Kell alloimmunity produces lower amniotic bilirubin levels and a lower reticulocyte count because, in addition to hemolysis, it inhibits erythropoiesis.


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Pediatrics_Nelson. Nonimmune causes of hemolysis in the newborn include RBC enzyme deficiencies of the Embden-Meyerhof pathway, such as pyruvate kinase or glucose-6-phosphate dehydrogenase deficiency. RBC membrane disorders are another cause of nonimmune hemolysis. Hereditary spherocytosis is inherited as a severe autosomal recessive form or less severe autosomal dominant form and is the result of a deficiency of spectrin, a protein of the RBC membrane. Hemoglobinopathies, such as thalassemia, are another cause of nonimmunologically mediated hemolysis. Available @ StudentConsult.com


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Pediatrics_Nelson. Anemia from blood loss at birth is manifested by two patterns of presentation, depending on the rapidity of blood loss.Acute blood loss after fetal-maternal hemorrhage, rupture ofthe umbilical cord, placenta previa, or internal hemorrhage (hepatic or splenic hematoma; retroperitoneal) is characterized by pallor, diminished peripheral pulses, and shock. Thereare no signs of extramedullary hematopoiesis and no hepatosplenomegaly. The hemoglobin content and serum iron levelsinitially are normal, but the hemoglobin levels decline duringthe subsequent 24 hours. Newborns with chronic blood loss caused by chronic fetal-maternal hemorrhage or a twin-totwin transfusion present with marked pallor, heart failure,hepatosplenomegaly with or without hydrops, a low hemoglobin level at birth, a hypochromic microcytic blood smear, anddecreased serum iron stores. Fetal-maternal bleeding occurs in50% to 75% of all pregnancies, with fetal blood losses rangingfrom 1 to 50 mL; most blood losses are 1 mL or


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Pediatrics_Nelson. microcytic blood smear, anddecreased serum iron stores. Fetal-maternal bleeding occurs in50% to 75% of all pregnancies, with fetal blood losses rangingfrom 1 to 50 mL; most blood losses are 1 mL or less, 1 in 400 are approximately 30 mL, and 1 in 2000 are approximately 100 mL.


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Pediatrics_Nelson. The diagnosis of fetal-maternal hemorrhage is confirmed by the Kleihauer-Betke acid elution test. Pink fetal RBCs are observed and counted in the mother’s peripheral blood smear because fetal hemoglobin is resistant to acid elution; adult hemoglobin is eluted, leaving discolored maternal cells (patients with sickle cell anemia or hereditary persistence of fetal hemoglobin may have a false-positive result, and ABO incompatibility may produce a false-negative result).


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Pediatrics_Nelson. Hemolysis in utero resulting from any cause may produce a spectrum of clinical manifestations at birth. Severe hydropswith anasarca, heart failure, and pulmonary edema may prevent adequate ventilation at birth, resulting in asphyxia. Infantsaffected with hemolysis in utero have hepatosplenomegaly andpallor and become jaundiced within the first 24 hours afterbirth. Less severely affected infants manifest pallor and hepatosplenomegaly at birth and become jaundiced subsequently.Patients with ABO incompatibility often are asymptomaticand show no physical signs at birth; mild anemia with jaundicedevelops during the first 24 to 72 hours of life.


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Pediatrics_Nelson. Because hydrops, anemia, or jaundice are secondary to many diverse causes of hemolysis, a laboratory evaluation is needed in all patients with suspected hemolysis. A complete blood count, blood smear, reticulocyte count, blood type, and direct Coombs test (to determine the presence of antibody-coated RBCs) should be performed in the initial evaluation of all infants with hemolysis. Reduced hemoglobin levels, reticulocytosis, and a blood smear characterized by polychromasia and anisocytosis are expected with isoimmune hemolysis. Spherocytes commonly are observed in ABO incompatibility. The determination of the blood type and the Coombs test identify the responsible antigen and antibody in immunologically mediated hemolysis.


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Pediatrics_Nelson. In the absence of a positive Coombs test and blood group differences between the mother and fetus, other causes of non-immune hemolysis must be considered. RBC enzyme assays, hemoglobin electrophoresis, or RBC membrane tests (osmotic fragility, spectrin assay) should be performed. Internal hemorrhage also may be associated with anemia, reticulocytosis, and jaundice when the hemorrhage reabsorbs; ultrasound evaluation of the brain, liver, spleen, or adrenal gland may be indicated when nonimmune hemolysis is suspected. Shock is more typical in patients with internal hemorrhage, whereas in hemolytic diseases, heart failure may be seen with severe anemia. Evaluation of a possible fetal-maternal hemorrhage should include the Kleihauer-Betke test.


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Pediatrics_Nelson. The treatment of symptomatic neonatal anemia is transfusion of cross-matched packed RBCs. If immune hemolysis is present,the cells to be transfused must be cross-matched against maternal and neonatal plasma. Acute volume loss may necessitateresuscitation with nonblood products, such as saline if bloodis not available; packed RBCs can be given subsequently. Tocorrect anemia and any remaining blood volume deficit, 10 to15 mL/kg of packed RBCs should be sufficient. Cytomegalovirus-seronegative blood should be given to cytomegalovirusseronegative infants, and all blood products should be irradiatedto reduce the risk of graft-versus-host disease; blood should bescreened for HIV, hepatitis B and C, and syphilis. Recombinanterythropoietin may improve the hematocrit in infants with ahyporegenerative anemia after in utero transfusion.


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Pediatrics_Nelson. Hemolytic disease of the newborn is a common cause of neonatal jaundice. Nonetheless, because of the immaturity of the pathways of bilirubin metabolism, many newborn infants without evidence of hemolysis become jaundiced.


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Pediatrics_Nelson. Bilirubin is produced by the catabolism of hemoglobin in the reticuloendothelial system. The tetrapyrrole ring of heme is cleaved by heme oxygenase to form equivalent quantities of biliverdin and carbon monoxide. Because no other biologic source of carbon monoxide exists, the excretion of this gas is stoichiometrically identical to the production of bilirubin. Biliverdin is converted to bilirubin by biliverdin reductase. One gram of hemoglobin produces 35 mg of bilirubin. Sources of bilirubin other than circulating hemoglobin represent 20% of bilirubin production; these sources include inefficient (shunt) hemoglobin production and lysis of precursor cells in bone marrow. Compared with adults, newborns have a twofold to threefold greater rate of bilirubin production (6 to 10 mg/kg/24 hr versus 3 mg/kg/24 hr). This increased production is caused, in part, by an increased RBC mass (higher hematocrit) and a shortened erythrocyte life span of 70 to 90 dayscompared with the 120-day


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Pediatrics_Nelson. hr versus 3 mg/kg/24 hr). This increased production is caused, in part, by an increased RBC mass (higher hematocrit) and a shortened erythrocyte life span of 70 to 90 dayscompared with the 120-day erythrocyte life span in adults.


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Pediatrics_Nelson. Bilirubin produced after hemoglobin catabolism is lipid soluble and unconjugated and reacts as an indirect reagent in the van den Bergh test. Indirect-reacting, unconjugated bilirubin is toxic to the central nervous system and is insoluble in water, limiting its excretion. Unconjugated bilirubin binds to albumin on specific bilirubin binding sites; 1 g of albumin binds 8.5 mg of bilirubin in a newborn. If the binding sites become saturated or if a competitive compound binds at the site, displacing bound bilirubin, free bilirubin becomes available to enter the central nervous system. Organic acids such as free fatty acids and drugs such as sulfisoxazole can displace bilirubin from its binding site on albumin.


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Pediatrics_Nelson. Bilirubin dissociates from albumin at the hepatocyte and becomes bound to a cytoplasmic liver protein Y (ligandin). Hepatic conjugation results in the production of bilirubin diglucuronide, which is water soluble and capable of biliary and renal excretion. The enzyme glucuronosyltransferase represents the rate-limiting step of bilirubin conjugation. The concentrations of ligandin and glucuronosyltransferase are lower in newborns, particularly in premature infants, than in older children.


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Pediatrics_Nelson. Conjugated bilirubin gives a direct reaction in the van den Bergh test. Most conjugated bilirubin is excreted through the bile into the small intestine and eliminated in the stool. Some bilirubin may undergo hydrolysis back to the unconjugated fraction by intestinal glucuronidase, however, and may be reabsorbed (enterohepatic recirculation). In addition, bacteria in the neonatal intestine convert bilirubin to urobilinogen and stercobilinogen, which are excreted in urine and stool and usually limit bilirubin reabsorption. Delayed passage of meconium, which contains bilirubin, also may contribute to the enterohepatic recirculation of bilirubin.


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Pediatrics_Nelson. Bilirubin is produced in utero by the normal fetus and by the fetus affected by erythroblastosis fetalis. Indirect, unconjugated, lipid-soluble fetal bilirubin is transferred across the placenta and becomes conjugated by maternal hepatic enzymes. The placenta is impermeable to conjugated water-soluble bilirubin. Fetal bilirubin levels become only mildly elevated in the presence of severe hemolysis, but may increase when hemolysis produces fetal hepatic inspissated bile stasis and conjugated hyperbilirubinemia. Maternal indirect (but not direct) hyperbilirubinemia also may increase fetal bilirubin levels. Etiology of Indirect Unconjugated Hyperbilirubinemia Decision-Making Algorithm Available @ StudentConsult.com


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Pediatrics_Nelson. Etiology of Indirect Unconjugated Hyperbilirubinemia Decision-Making Algorithm Available @ StudentConsult.com Physiologic jaundice is a common cause of hyperbilirubinemia among newborns. It is a diagnosis of exclusion, made after careful evaluation has ruled out more serious causes of jaundice, such as hemolysis, infection, and metabolic diseases. Physiologic jaundice is the result of many factors that are normal physiologic characteristics of newborns: increased bilirubin production resulting from an increased RBC mass, shortened RBC life span, and hepatic immaturity of ligandin and glucuronosyltransferase. Physiologic jaundice may be exaggerated among infants of Greek and Asian ancestry.


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Pediatrics_Nelson. The clinical pattern of physiologic jaundice in term infantsincludes a peak indirect-reacting bilirubin level of no morethan 12 mg/dL on day 3 of life. In premature infants, the peakis higher (15 mg/dL) and occurs later (fifth day). The peak levelof indirect bilirubin during physiologic jaundice may be higherin breast milk–fed infants than in formula-fed infants (15 to17 mg/dL versus 12 mg/dL). This higher level may be partly aresult of the decreased fluid intake of infants fed breast milk. Jaundice is unphysiologic or pathologic if it is clinically evidenton the first day of life, if the bilirubin level increases more than 0.5 mg/dL/hr, if the peak bilirubin is greater than 13 mg/dLin term infants, if the direct bilirubin fraction is greater than 1.5 mg/dL, or if hepatosplenomegaly and anemia are present.


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Pediatrics_Nelson. Crigler-Najjar syndrome is a serious, rare, autosomal recessive, permanent deficiency of glucuronosyltransferase that results in severe indirect hyperbilirubinemia. Type II responds to enzyme induction by phenobarbital, producing an increase in enzyme activity and a reduction of bilirubin levels. Type I does not respond to phenobarbital and manifests as persistent indirect hyperbilirubinemia, often leading to kernicterus. Gilbert disease is caused by a mutation of the promoter region of glucuronosyltransferase and results in a mild indirect hyperbilirubinemia. In the presence of another icterogenic factor (hemolysis), more severe jaundice may develop. Hepatic infarction Inborn errors of metabolism (galactosemia, tyrosinemia) Cystic fibrosis Biliary atresia Choledochal cyst α1-Antitrypsin deficiency Neonatal iron storage disease Alagille syndrome (arteriohepatic dysplasia) Byler disease CMV, Cytomegalovirus; TORCH, toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex.


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Pediatrics_Nelson. Direct-reacting hyperbilirubinemia (defined as a direct bilirubin level >2 mg/dL or >20% of the total bilirubin) is never physiologic and should always be evaluated thoroughly according to the diagnostic categories (Table 62-2). Direct-reacting bilirubin (composed mostly of conjugated bilirubin) is not neurotoxic to the infant but signifies a serious underlying disorder involving cholestasis or hepatocellular injury. The diagnostic evaluation of patients with direct-reacting hyperbilirubinemia involves the determination of the levels of liver enzymes (aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and γ-glutamyl transpeptidase), bacterial and viral cultures, metabolic screening tests, hepatic ultrasound, sweat chloride test, and occasionally liver biopsy. In addition, the presence of dark urine and gray-white (acholic) stools with jaundice after the second week of life strongly suggests biliary atresia. The treatment of disorders manifested by direct


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Pediatrics_Nelson. In addition, the presence of dark urine and gray-white (acholic) stools with jaundice after the second week of life strongly suggests biliary atresia. The treatment of disorders manifested by direct bilirubinemia is specific for the diseases that are listed in Table 62-2. These diseases do not respond to phototherapy or exchange transfusion.


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Pediatrics_Nelson. Lipid-soluble, unconjugated, indirect bilirubin fraction is toxic to the developing central nervous system, especially when indirect bilirubin concentrations are high and exceed the binding capacity of albumin. Kernicterus results when indirect bilirubin is deposited in brain cells and disrupts neuronal metabolism and function, especially in the basal ganglia. Indirect bilirubin may cross the blood-brain barrier because of its lipid solubility. Other theories propose that a disruption of the blood-brain barrier permits entry of a bilirubin-albumin or free bilirubin–fatty acid complex. Kernicterus usually is noted when the bilirubin level is excessively high for gestational age. It usually does not develop in term infants when bilirubin levels are less than 20 to Common Blood group Physiologic jaundice, incompatibility: ABO, Rh, breast milk jaundice, Kell, Duffy infection internal hemorrhage, polycythemia, infant of diabetic mother


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Pediatrics_Nelson. Common Blood group Physiologic jaundice, incompatibility: ABO, Rh, breast milk jaundice, Kell, Duffy infection internal hemorrhage, polycythemia, infant of diabetic mother Rare Red blood cell enzyme defects: glucose-6-phosphate dehydrogenase, pyruvate kinase Red blood cell membrane disorders: spherocytosis, ovalocytosis Hemoglobinopathy: thalassemia Mutations of glucuronyl transferase enzyme (Crigler-Najjar syndrome, Gilbert disease), pyloric stenosis, hypothyroidism, immune thrombocytopenia


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Pediatrics_Nelson. Breast milk jaundice may be associated with unconjugated hyperbilirubinemia without evidence of hemolysis during the first to second week of life. Bilirubin levels rarely increase to more than 20 mg/dL. Interruption of breastfeeding for 1 to 2 days results in a rapid decline of bilirubin levels, which do not increase significantly after breastfeeding resumes. Breast milk may contain an inhibitor of bilirubin conjugation or may increase enterohepatic recirculation of bilirubin because of breast milk glucuronidase. Jaundice on the first day of life is always pathologic, and immediate attention is needed to establish the cause. Early onset often is a result of hemolysis, internal hemorrhage (cephalhematoma, hepatic or splenic hematoma), or infection (Table 62-1). Infection also is often associated with direct-reacting bilirubin resulting from perinatal congenital infections or from bacterial sepsis.


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Pediatrics_Nelson. Physical evidence of jaundice is observed in infants when bilirubin levels reach 5 to 10 mg/dL (versus 2 to 3 mg/dL in adults). When jaundice is observed, the laboratory evaluation for hyperbilirubinemia should include a total bilirubin measurement to determine the magnitude of hyperbilirubinemia. Bilirubin levels greater than 5 mg/dL on the first day of life or greater than 13 mg/dL thereafter in term infants should be evaluated further with measurement of indirect and direct bilirubin levels, blood typing, Coombs test, complete blood count, blood smear, and reticulocyte count. These tests must be performed before treatment of hyperbilirubinemia with phototherapy or exchange transfusion. In the absence of hemolysis or evidence for either the common or the rare causes of nonhemolytic indirect hyperbilirubinemia, the diagnosis is either physiologic or breast milk jaundice. Jaundice present after 2 weeks of age is pathologic and suggests a direct-reacting hyperbilirubinemia.


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Pediatrics_Nelson. Etiology of Direct Conjugated Hyperbilirubinemia Available @ StudentConsult.com 25 mg/dL, but the incidence increases as serum bilirubin levels exceed 25 mg/dL. Kernicterus may be noted at bilirubin levels less than 20 mg/dL in the presence of sepsis, meningitis, hemolysis, asphyxia, hypoxia, hypothermia, hypoglycemia, bilirubin-displacing drugs (sulfa drugs), and prematurity. Other risks for kernicterus in term infants are hemolysis, jaundice noted within 24 hours of birth, and delayed diagnosis of hyperbilirubinemia. Kernicterus has developed in extremely immature infants weighing less than 1000 g when bilirubin levels are less than 10 mg/dL because of a more permeable blood-brain barrier associated with prematurity.


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Pediatrics_Nelson. The earliest clinical manifestations of kernicterus are lethargy, hypotonia, irritability, poor Moro response, and poor feeding. A high-pitched cry and emesis also may be present.Early signs are noted after day 4 of life. Later signs includebulging fontanelle, opisthotonic posturing, pulmonary hemorrhage, fever, hypertonicity, paralysis of upward gaze, andseizures. Infants with severe cases of kernicterus die in the neonatal period. Spasticity resolves in surviving infants, who maymanifest later nerve deafness, choreoathetoid cerebral palsy,mental retardation, enamel dysplasia, and discoloration ofteeth as permanent sequelae. Kernicterus may be prevented byavoiding excessively high indirect bilirubin levels and by avoiding conditions or drugs that may displace bilirubin from albumin. Early signs of kernicterus occasionally may be reversedby immediately instituting an exchange transfusion (see later). Therapy of Indirect Hyperbilirubinemia


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Pediatrics_Nelson. Therapy of Indirect Hyperbilirubinemia Phototherapy is an effective and safe method for reducing indirect bilirubin levels, particularly when initiated before serum bilirubin increases to levels associated with kernicterus. In term infants, phototherapy is begun when indirect bilirubin levels are between 16 and 18 mg/dL. Phototherapy is initiated in premature infants when bilirubin is at lower levels, to prevent bilirubin from reaching the high concentrations necessitating exchange transfusion. Blue lights and white lights are effective in reducing bilirubin levels.


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Pediatrics_Nelson. Under the effects of phototherapy light with maximal irradiance in the 425to 475-nm wavelength band, bilirubin is transformed into isomers that are water soluble and easily excreted. Unconjugated bilirubin (IX) is in the 4Z, 15Z configuration. Phototherapy causes a photochemical reaction producing the reversible, more water-soluble isomer 4Z, 15E bilirubin IX. This isomer can be excreted easily, bypassing the liver’s conjugation system. Another photochemical reaction results in the rapid production of lumirubin, a more water-soluble isomer than the aforementioned isomer, which does not spontaneously revert to unconjugated native bilirubin and can be excreted in urine.


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Pediatrics_Nelson. Complications of phototherapy include an increased insensible water loss, diarrhea, and dehydration. Additional problems are macular-papular red skin rash, lethargy, masking of cyanosis, nasal obstruction by eye pads, and potential for retinal damage. Skin bronzing may be noted in infants with direct-reacting hyperbilirubinemia. Infants with mild hemolytic disease of the newborn occasionally may be managed successfully with phototherapy for hyperbilirubinemia, but care must be taken to follow these infants for the late occurrence of anemia from continued hemolysis.


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Pediatrics_Nelson. Exchange transfusion usually is reserved for infants with dangerously high indirect bilirubin levels who are at risk for kernicterus. As a rule of thumb, a level of 20 mg/dL for indirect-reacting bilirubin is the exchange number for infants with hemolysis who weigh more than 2000 g. Asymptomatic infants with physiologic or breast milk jaundice may not require exchange transfusion, unless the indirect bilirubin level exceeds 25 mg/dL. The exchangeable level of indirect bilirubin for other infants may be estimated by calculating 10% of the birth weight in grams: the level in an infant weighing 1500 g would be 15 mg/dL. Infants weighing less than 1000 g usually do not require an exchange transfusion until the bilirubin level exceeds 10 mg/dL.


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Pediatrics_Nelson. The exchange transfusion usually is performed through an umbilical venous catheter placed in the inferior vena cava or, if free flow is obtained, at the confluence of the umbilical vein and the portal system. The level of serum bilirubin immediately after the exchange transfusion declines to levels that are about half of those before the exchange; levels rebound 6 to 8 hours later as a result of continued hemolysis and redistribution of bilirubin from tissue stores. Complications of exchange transfusion include problems related to the blood (transfusion reaction, metabolic instability, or infection), the catheter (vessel perforation or hemorrhage), or the procedure (hypotension or necrotizing enterocolitis [NEC]). Unusual complications include thrombocytopenia and graft-versus-host disease. Continuation of phototherapy may reduce the necessity for subsequent exchange transfusions.


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Pediatrics_Nelson. Polycythemia is an excessively high hematocrit (≥65%), which may lead to hyperviscosity that produces symptoms related to vascular stasis, hypoperfusion, and ischemia. As the hematocrit increases from 40% to 60%, there is a small increase in blood viscosity. When the central hematocrit increases to greater than 65%, the blood viscosity begins to increase markedly, and symptoms may appear. Neonatal erythrocytes are less filterable or deformable than adult erythrocytes, which further contributes to hyperviscosity. A central venous hematocrit of 65% or greater is noted in 3% to 5% of infants. Infants at special risk for polycythemia are term and post-term small for gestational age infants, infants of diabetic mothers, infants with delayed cord clamping, and infants with neonatal hyperthyroidism, adrenogenital syndrome, trisomy 13, trisomy 18, trisomy 21, twin-to-twin transfusion syndrome (recipient), or Beckwith-Wiedemann syndrome. In some infants, polycythemia may reflect a compensation


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Pediatrics_Nelson. adrenogenital syndrome, trisomy 13, trisomy 18, trisomy 21, twin-to-twin transfusion syndrome (recipient), or Beckwith-Wiedemann syndrome. In some infants, polycythemia may reflect a compensation for prolonged periods of fetal hypoxia caused by placental insufficiency; these infants have increased erythropoietin levels at birth.


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Pediatrics_Nelson. Polycythemic patients appear plethoric or ruddy and may develop acrocyanosis. Symptoms are a result of the increased RBC mass and of vascular compromise. Seizures, lethargy, and irritability reflect abnormalities of microcirculation of the brain, whereas hyperbilirubinemia may reflect the poor hepatic circulation or the increased amount of hemoglobin that is being broken down into bilirubin. Additional problems include respiratory distress and primary pulmonary hypertension of the newborn (PPHN) that result in part from elevated pulmonary vascular resistance. The chest radiograph often reveals cardiomegaly, increased vascular markings, pleural effusions, and interstitial edema. Other problems are NEC, hypoglycemia, thrombocytopenia, priapism, testicular infarction, hemiplegic stroke, and feeding intolerance. Many of these complications also are related to the primary condition associated with polycythemia (small for gestational age infants are at risk for hypoglycemia and PPHN after


Pediatrics_Nelson

Pediatrics_Nelson. feeding intolerance. Many of these complications also are related to the primary condition associated with polycythemia (small for gestational age infants are at risk for hypoglycemia and PPHN after periods of hypoxia in utero).


Pediatrics_Nelson

Pediatrics_Nelson. Long-term sequelae of neonatal polycythemia relate to neurodevelopmental abnormalities that may be prevented by treatment of symptomatic infants with partial exchange transfusion after birth. A partial exchange transfusion removes whole blood and replaces it with normal saline. The equation used to calculate the volume exchanged is based on the central venous hematocrit because peripheral hematocrits may be falsely elevated: Volume to exchange(mL) = [blood volume× (observed hematocrit −desired hematocrit)]/observed hematocrit The desired hematocrit is 50%, and the blood volume 85 mL/kg.


Pediatrics_Nelson

Pediatrics_Nelson. Volume to exchange(mL) = [blood volume× (observed hematocrit −desired hematocrit)]/observed hematocrit The desired hematocrit is 50%, and the blood volume 85 mL/kg. Disorders of coagulation are common in the neonatal period. Hemorrhage during this time may be a result of trauma, inherited permanent deficiency of coagulation factors, transient deficiencies of vitamin K–dependent factors, disorders of platelets, and disseminated intravascular coagulation (DIC) seen in sick newborns with shock or hypoxia. Thrombosis also is a potential problem in the newborn because of developmentally lower circulating levels of antithrombin III, protein C (a vitamin K–dependent protein that inhibits factors VIII and V), and the fibrinolytic system.


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Pediatrics_Nelson. Coagulation factors do not pass through the placenta to the fetus, and newborn infants have relatively low levels of the vitamin K–dependent factors II, VII, IX, and X. Contact factors XI and XII, prekallikrein, and kininogen also are lower in newborns than in adults. Fibrinogen (factor I); plasma levels of factors V, VIII, and XIII; and platelet counts are within the adult normal range. Because of the transient, relative deficiencies of the contact and vitamin K–dependent factors, the partial thromboplastin time (PTT), which is dependent on factors XII, IX, VIII, X, V, II, and I, is prolonged in the newborn period. Preterm infants have the most marked prolongation of the PTT (50 to 80 seconds) compared with term infants (35 to 50 seconds) and older, more mature infants (25 to 35 seconds). The administration of heparin and the presence of DIC, hemophilia, and severe vitamin K deficiency prolong the PTT.


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Pediatrics_Nelson. The prothrombin time (PT), which is dependent on factors X, VII, V, II, and I, is a more sensitive test for vitamin K deficiency. The PT is only slightly prolonged in term infants (13 to 20 seconds) compared with preterm infants (13 to 21 seconds) and more mature patients (12 to 14 seconds). Abnormal prolongations of the PT occur with vitamin K deficiency, hepatic injury, and DIC. Levels of fibrinogen and fibrin degradation products are similar in infants and adults. The bleeding time, which reflects platelet function and number, is normal during the newborn period in the absence of maternal salicylate therapy.


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Pediatrics_Nelson. Vitamin K is a necessary cofactor for the carboxylation of glutamate on precursor proteins, converting them into the more active coagulation factors II, VII, IX, and X; γcarboxyglutamic acid binds calcium, which is required for the immediate activation of factors during hemorrhage. There is no congenital deficiency of hepatic synthesis of these precursor proteins, but in the absence of vitamin K their conversion to the active factor is not possible. Levels of protein induced by vitamin K absence increase in vitamin K deficiency and are helpful diagnostic markers; vitamin K administration rapidly corrects the coagulation defects, reducing protein induced by vitamin K absence to undetectable levels.


Pediatrics_Nelson

Pediatrics_Nelson. Although most newborns are born with reduced levels of vitamin K–dependent factors, hemorrhagic complications develop only rarely. Infants at risk for hemorrhagic disease of the newborn have the most profound deficiency of vitamin K–dependent factors, and these factors decline further after birth. Because breast milk is a poor source of vitamin K, breastfed infants are at increased risk for hemorrhage that usually occurs between days 3 and 7 of life. Bleeding usually ensues from the umbilical cord, circumcision site, intestines, scalp, mucosa, and skin, but internal hemorrhage places the infant at risk for fatal complications, such as intracranial bleeding.


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Pediatrics_Nelson. Hemorrhage on the first day of life resulting from a deficiency of the vitamin K–dependent factors often is associated with administration to the mother of drugs that affect vitamin K metabolism in the infant. This early pattern of hemorrhage has been seen with maternal warfarin or antibiotic (e.g., isoniazid or rifampin) therapy and in infants of mothers receiving phenobarbital and phenytoin. Bleeding also may occur 1 to 3 months after birth, particularly among breastfed infants. Vitamin K deficiency in breastfed infants also should raise suspicion about the possibility of vitamin K malabsorption resulting from cystic fibrosis, biliary atresia, hepatitis, or antibiotic suppression of the colonic bacteria that produce vitamin K.


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Pediatrics_Nelson. Bleeding associated with vitamin K deficiency may be prevented by administration of vitamin K to all infants at birth. Before routine administration of vitamin K, 1% to 2% of all newborns had hemorrhagic disease of the newborn. One intramuscular dose (1 mg) of vitamin K prevents vitamin K–deficiency bleeding. Treatment of bleeding resulting from vitamin K deficiency involves intravenous administration of 1 mg of vitamin K. If severe, life-threatening hemorrhage is present, fresh frozen plasma also should be given. Unusually high doses of vitamin K may be needed for hepatic disease and for maternal warfarin or anticonvulsant therapy. Clinical Manifestations and Differential Diagnoses of Bleeding Disorders Available @ StudentConsult.com


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Pediatrics_Nelson. Clinical Manifestations and Differential Diagnoses of Bleeding Disorders Available @ StudentConsult.com Bleeding disorders in a newborn may be associated with cutaneous bleeding, such as cephalhematoma, subgaleal hemorrhage, ecchymosis, and petechiae. Facial petechiae are common in infants born by vertex presentation, with or without a nuchal cord, and usually are insignificant. Mucosal bleeding may appear as hematemesis, melena, or epistaxis. Internal hemorrhage results in organ-specific dysfunction, such as seizures associated with intracranial hemorrhage. Bleeding from venipuncture or heel-stick sites, circumcision sites, or the umbilical cord also is common.


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Pediatrics_Nelson. The differential diagnosis depends partly on the clinical circumstances associated with the hemorrhage. In a sick newborn, the differential diagnosis should include DIC, hepatic failure, and thrombocytopenia. Thrombocytopenia in an ill neonate may be secondary to consumption by trapping of platelets in a hemangioma (Kasabach-Merritt syndrome)or may be associated with perinatal, congenital, or bacterial infections; NEC; thrombotic endocarditis; PPHN; organic acidemia; maternal preeclampsia; or asphyxia. Thrombocytopenia also may be due to peripheral washout of platelets after an exchange transfusion. Treatment of a sick infant with thrombocytopenia should be directed at the underlying disorder, supplemented by infusions of platelets, blood, or both.


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Pediatrics_Nelson. The etiology of DIC in a newborn includes hypoxia, hypo-tension, asphyxia, bacterial or viral sepsis, NEC, death of a twin while in utero, cavernous hemangioma, nonimmune hydrops, neonatal cold injury, neonatal neoplasm, and hepatic disease. The treatment of DIC should be focused primarily on therapy for the initiating or underlying disorder. Supportive management of consumptive coagulopathy involves platelet transfusions and factor replacement with fresh frozen plasma. Heparin and factor C concentrate should be reserved for infants with DIC who also have thrombosis. Disorders of hemostasis in a well child are not associated with systemic disease in a newborn but reflect coagulation factor or platelet deficiency. Hemophilia initially is associated with cutaneous or mucosal bleeding and no systemic illness. If bleeding continues, hypovolemic shock may develop. Bleeding into the brain, liver, or spleen may result in organ-specific signs and shock.


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Pediatrics_Nelson. In a well child, thrombocytopenia may be part of a syndrome such as Fanconi anemia syndrome (involving hypoplasia and aplasia of the thumb), radial aplasia-thrombocytopenia syndrome (thumbs present), or Wiskott-Aldrich syndrome. Various maternal drugs also may reduce the neonatal platelet count without producing other adverse effects. These drugs include sulfonamides, quinidine, quinine, and thiazide diuretics.


Pediatrics_Nelson

Pediatrics_Nelson. The most common causes of thrombocytopenia in wellnewborns are transient isoimmune thrombocytopenia andtransient neonatal thrombocytopenia. Isoimmune thrombocytopenia is caused by antiplatelet antibodies producedby the HPLA1-negative mother after her sensitization to specific paternal platelet antigen (HPA-1a and HPA-5b represent85% and 10% of cases, respectively) expressed on the fetalplatelet. The incidence is 1 in 1000 to 1 in 2000 births. Thisresponse to maternal-sensitized antibodies that produce isoimmune thrombocytopenia is analogous to the response thatproduces erythroblastosis fetalis. The maternal antiplateletantibody does not produce maternal thrombocytopenia, butafter crossing the placenta this IgG antibody binds to fetalplatelets that are trapped by the reticuloendothelial tissue,resulting in thrombocytopenia. Infants with thrombocytopenia produced in this manner are at risk for developmentof petechiae, purpura, and intracranial hemorrhage (an incidence of 10% to 15%)


Pediatrics_Nelson

Pediatrics_Nelson. tissue,resulting in thrombocytopenia. Infants with thrombocytopenia produced in this manner are at risk for developmentof petechiae, purpura, and intracranial hemorrhage (an incidence of 10% to 15%) before or after birth. Vaginal deliverymay increase the risk of neonatal bleeding; cesarean sectionmay be indicated.


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Pediatrics_Nelson. Specific treatment for severe thrombocytopenia (<20,000 platelets/mm3) or significant bleeding is transfusion of ABO-compatible and RhD-compatible, HPA-1a-negative and HPA-5b-negative maternal platelets. Because the antibody in isoimmune thrombocytopenia is directed against the fetal rather than the maternal platelet, thrombocytapheresis of the mother yields sufficient platelets to treat the affected infant. After one platelet transfusion, the infant’s platelet count dramatically increases and usually remains in a safe range. Without treatment, thrombocytopenia resolves during the first month of life as the maternal antibody level declines. Treatment of the mother with intravenous immunoglobulin or the thrombocytopenic fetus with intravascular platelet transfusion (cordocentesis) is also effective. Cesarean section reduces the risk of intracranial hemorrhage.


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Pediatrics_Nelson. Neonatal thrombocytopenia in infants born to women withidiopathic thrombocytopenic purpura (ITP) also is a result of placental transfer of maternal IgG antibodies. In ITP, these auto-antibodies are directed against all platelet antigens; mother andnewborn may have low platelet counts. The risks of hemorrhagein an infant born to a mother with ITP may be lessened by cesarean section and by treatment of the mother with corticosteroids.


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Pediatrics_Nelson. Treatment of an affected infant born to a mother with ITP may involve prednisone and intravenous immunoglobulin. In an emergency, random donor platelets may be used and may produce a transient increase in the infant’s platelet count. Thrombocytopenia resolves spontaneously during the first month of life as maternal-derived antibody levels decline. Elevated levels of platelet-associated antibodies also have been noted in thrombocytopenic infants with sepsis and thrombocytopenia of unknown cause who were born to mothers without demonstrable platelet antibodies.


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Pediatrics_Nelson. The laboratory evaluation of an infant (well or sick) with bleeding must include a platelet count, blood smear, and evaluation of PTT and PT. Isolated thrombocytopenia in a well infant suggests immune thrombocytopenia. Laboratory evidence of DIC includes a markedly prolonged PTT and PT (minutes rather than seconds), thrombocytopenia, and a blood smear suggesting a microangiopathic hemolytic anemia (burr or fragmented blood cells). Further evaluation reveals low levels of fibrinogen (<100 mg/dL) and elevated levels of fibrin degradation products. Vitamin K deficiency prolongs the PT more than the PTT, whereas hemophilia resulting from factors VIII and IX deficiency prolongs only the PTT. Specific factor levels confirm the diagnosis of hemophilia.


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Pediatrics_Nelson. Necrotizing enterocolitis (NEC) is a syndrome of intestinal injury and is the most common intestinal emergency occurring in preterm infants admitted to the neonatal intensive care unit. NEC occurs in 1 to 3 per 1000 live births and 1% to 8% of admissions to the neonatal intensive care unit. Prematurity is the most consistent and significant factor associated with neonatal NEC. The disease occurs in 4% to 13% of infants who weigh less than 1500 g at birth. NEC is infrequent in term infants (<10% of affected infants).


Pediatrics_Nelson

Pediatrics_Nelson. Most cases of NEC occur in premature infants born before 34 weeks’ gestation who have been fed enterally. Prematurity is associated with immaturity of the gastrointestinal tract, including decreased integrity of the intestinal mucosal barrier, depressed mucosal enzymes, suppressed gastrointestinal hormones, suppressed intestinal host defense system, decreased coordination of intestinal motility, and differences in blood flow autoregulation, which is thought to play a significant role in the pathogenesis of NEC. More than 90% of infants diagnosed with NEC have been fed enterally, but NEC has been reported in infants who have never been fed. Feeding with human milk has shown a beneficial role in reducing the incidence of NEC. In addition, probiotics may offer potential benefits for the preterm infant by increasing mucosal barrier function, improving nutrition, upregulating the immune system, and reducing mucosal colonization by potential pathogens. It also is theorized that compromised


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Pediatrics_Nelson. infant by increasing mucosal barrier function, improving nutrition, upregulating the immune system, and reducing mucosal colonization by potential pathogens. It also is theorized that compromised intestinal blood flow contributes to NEC.


Pediatrics_Nelson

Pediatrics_Nelson. Early clinical signs of NEC include abdominal distention,feeding intolerance/increased gastric residuals, emesis, rectalbleeding, and occasional diarrhea. As the disease progresses,patients may develop marked abdominal distention, biliousemesis, ascites, abdominal wall erythema, lethargy, temperatureinstability, increased episodes of apnea/bradycardia, disseminated intravascular coagulation, and shock. With abdominalperforation, the abdomen may develop a bluish discoloration. The white blood cell count can be elevated, but often it is depressed. Thrombocytopenia is common. In addition, infants may develop coagulation abnormalities along with metabolic derangements, including metabolic acidosis, electrolyte imbalance, and hypoglycemia and hyperglycemia. No unique infectious agent has been associated with NEC; bacteriologic and fungal cultures may prove helpful but not conclusive.


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Pediatrics_Nelson. Radiographic imaging is essential to the diagnosis of NEC.The earliest radiographic finding is intestinal ileus, often associated with thickening of the bowel loops and air-fluid levels. Thepathognomonic radiographic finding is pneumatosis intestinalis caused by hydrogen gas production from pathogenic bacteria present between the subserosal and muscularis layers ofthe bowel wall. Radiographic findings also may include a fixedor persistent dilated loop of bowel, intrahepatic venous gas, andpneumoperitoneum seen with bowel perforation.


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Pediatrics_Nelson. The differential diagnosis of NEC includes sepsis with intestinal ileus or a volvulus. Both conditions can present with systemic signs of sepsis and abdominal distention. The absence of pneumatosis on abdominal radiographs does not rule out the diagnosis of NEC; other causes of abdominal distention and perforation (gastric or ileal perforation) should be considered and investigated. Patients diagnosed with Hirschsprung enterocolitis or severe gastroenteritis may present with pneumatosis intestinalis.


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Pediatrics_Nelson. The management of NEC includes the discontinuation of enteral feedings, gastrointestinal decompression with nasogastric suction, fluid and electrolyte replacement, total parenteralnutrition, and systemic broad-spectrum antibiotics. When thediagnosis of NEC is made, consultation with a pediatric surgeon should be obtained. Even with aggressive and appropriate medical management, 25% to 50% of infants with NEC requiresurgical intervention. The decision to perform surgery is obvious when the presence of a pneumoperitoneum is observed onabdominal radiograph. Other, not so obvious indications forsurgical intervention include rapid clinical deterioration despitemedical therapy, rapid onset and progression of pneumatosis,abdominal mass, and intestinal obstruction. The surgical procedure of choice is laparotomy with removal of the franklynecrotic and nonviable bowel. Many extremely small infants aremanaged initially with primary peritoneal drainage followed bysurgical intervention as needed


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Pediatrics_Nelson. is laparotomy with removal of the franklynecrotic and nonviable bowel. Many extremely small infants aremanaged initially with primary peritoneal drainage followed bysurgical intervention as needed later, when the infant is stableand a laparotomy can be performed safely. The long-term outcome includes intestinal strictures requiring further surgicalintervention, short bowel syndrome with poor absorption ofenteral fluids and nutrients, associated cholestasis with resultant cirrhosis and liver failure from prolonged parenteral nutrition,and neurodevelopmental delay from prolonged hospitalization.


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Pediatrics_Nelson. HYPOXIC-ISCHEMIC ENCEPHALOPATHY, INTRACRANIAL HEMORRHAGE, AND SEIZURES


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Pediatrics_Nelson. The human newborn spends more time asleep (predominantly in rapid eye movement or active sleep) than in a wakeful state and is totally dependent on adults. Primitive reflexes, such as the Moro, grasp, stepping, rooting, sucking, and crossed extensor reflexes, are readily elicited and are normal for this age. In addition, the newborn has a wealth of cortical functions that are less easily shown (e.g., the ability to extinguish repetitive or painful stimuli). The newborn also has the capacity for attentive eye fixation and differential responses to the mother’s voice. During the perinatal period, many pathophysiologic mechanisms can adversely and permanently affect the developing brain, including prenatal events, such as hypoxia, ischemia, infections, inflammation, malformations, maternal drugs, and coagulation disorders, as well as postnatal events, such as birth trauma, hypoxia-ischemia, inborn errors of metabolism, hypoglycemia, hypothyroidism, hyperthyroidism, polycythemia,


Pediatrics_Nelson

Pediatrics_Nelson. drugs, and coagulation disorders, as well as postnatal events, such as birth trauma, hypoxia-ischemia, inborn errors of metabolism, hypoglycemia, hypothyroidism, hyperthyroidism, polycythemia, hemorrhage, and meningitis.


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Pediatrics_Nelson. Available @ StudentConsult.com Focal clonic Repetitive, rhythmic contractions of muscle groups of the limbs, face, or trunk May be unilateral or multifocal May appear synchronously or asynchronously in various body regions Cannot be suppressed by restraint Focal tonic Sustained posturing of single limbs Sustained asymmetric posturing of the trunk Myoclonic Arrhythmic contractions of muscle groups of the limbs, face, or trunk Typically not repetitive or may recur at a slow rate May be generalized, focal, or fragmentary May be provoked by stimulation Generalized tonic Sustained symmetric posturing of limbs, trunk, and neck May be flexor, extensor, or mixed extensor/flexor May be provoked by stimulation May be suppressed by restraint or repositioning Orobuccolingual movements Sucking, chewing, tongue protrusions May be provoked by stimulation Progression movements Rowing or swimming movements of the arms Pedaling or bicycling movements of the legs


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Pediatrics_Nelson. Progression movements Rowing or swimming movements of the arms Pedaling or bicycling movements of the legs From Mizrahi EM: Neonatal seizures. In Shinnar S, Branski D, editors: Pediatric and adolescent medicine, vol 6, Childhood seizures, Basel, 1995, S. Karger.


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Pediatrics_Nelson. Seizures during the neonatal period may be the result of of a subarachnoid hemorrhage. Focal seizures often are the multiple causes, with characteristic historical and clini-result of local cerebral infarction. cal manifestations. Seizures caused by hypoxic-ischemic Seizures may be difficult to differentiate from benign encephalopathy (postasphyxial seizures), a common cause jitteriness or from tremulousness in infants of diabetic of seizures in the full-term infant, usually occur 12 to 24 mothers, in infants with narcotic withdrawal syndrome, hours after a history of birth asphyxia and often are refrac-and in any infants after an episode of asphyxia. In contrast tory to conventional doses of anticonvulsant medications. to seizures, jitteriness and tremors are sensory dependent, Postasphyxial seizures also may be caused by metabolic elicited by stimuli, and interrupted by holding the extremdisorders associated with neonatal asphyxia, such as hypo-ity. Seizure activity becomes


Pediatrics_Nelson

Pediatrics_Nelson. seizures also may be caused by metabolic elicited by stimuli, and interrupted by holding the extremdisorders associated with neonatal asphyxia, such as hypo-ity. Seizure activity becomes manifested as coarse, fast and glycemia and hypocalcemia. Intraventricular hemorrhage slow clonic activity, whereas jitteriness is characterized (IVH) is a common cause of seizures in premature infants by fine, rapid movement. Seizures may be associated with and often occurs between 1 and 3 days of age. Seizures with abnormal eye movements, such as tonic deviation to one IVH are associated with a bulging fontanelle, hemorrhagic side. The electroencephalogram often shows seizure activspinal fluid, anemia, lethargy, and coma. Seizures caused by ity when the clinical diagnosis is uncertain. Identifying hypoglycemia often occur when blood glucose levels decline seizures in the newborn period is often difficult because to the lowest postnatal value (at 1 to 2 hours of age or after the infant, especially


Pediatrics_Nelson

Pediatrics_Nelson. often occur when blood glucose levels decline seizures in the newborn period is often difficult because to the lowest postnatal value (at 1 to 2 hours of age or after the infant, especially the low birth weight infant, usually 24 to 48 hours of poor nutritional intake). Seizures caused by does not show the tonic-clonic major motor activity typical hypocalcemia and hypomagnesemia develop in high-risk of the older child (Table 64-1). Subtle seizures are a com-infants and respond well to therapy with calcium, magne-mon manifestation in newborns. The subtle signs of seizure sium, or both. activity include apnea, eye deviation, tongue thrusting, eye


Pediatrics_Nelson

Pediatrics_Nelson. Seizures noted in the delivery room often are caused by blinking, fluctuation of vital signs, and staring. Continudirect injection of local anesthetic agents into the fetal scalp ous bedside electroencephalographic monitoring can help (associated with transient bradycardia and fixed dilated identify subtle seizures. pupils), severe anoxia, or congenital brain malformation. The diagnostic evaluation of infants with seizures should Seizures after the first 5 days of life may be the result of involve an immediate determination of capillary blood gluinfection or drug withdrawal. Seizures associated with leth-cose levels with a Chemstrip. In addition, blood concenargy, acidosis, and a family history of infant deaths may trations of sodium, calcium, glucose, and bilirubin should be the result of an inborn error of metabolism. An infant be determined. When infection is suspected, cerebrospinal whose parent has a history of a neonatal seizure also is at fluid and blood specimens should be


Pediatrics_Nelson

Pediatrics_Nelson. of an inborn error of metabolism. An infant be determined. When infection is suspected, cerebrospinal whose parent has a history of a neonatal seizure also is at fluid and blood specimens should be obtained for culture. risk for benign familial seizures. In an infant who appears After the seizure has stopped, a careful examination should well, a sudden onset on day 1 to 3 of life of seizures that are be done to identify signs of increased intracranial pressure, of short duration and that do not recur may be the result congenital malformations, and systemic illness. If signs of elevated intracranial pressure are absent, a lumbar puncture should be performed. If the diagnosis is not apparentat this point, further evaluation should involve magneticresonance imaging, computed tomography, or cerebralultrasound and tests to determine the presence of an inbornerror of metabolism. Determinations of inborn errors of metabolism are especially important in infants with unexplained lethargy,


Pediatrics_Nelson

Pediatrics_Nelson. or cerebralultrasound and tests to determine the presence of an inbornerror of metabolism. Determinations of inborn errors of metabolism are especially important in infants with unexplained lethargy, coma, acidosis, ketonuria, or respiratoryalkalosis.


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Pediatrics_Nelson. The treatment of neonatal seizures may be specific, such as treatment of meningitis or the correction of hypoglycemia, hypocalcemia, hypomagnesemia, hyponatremia, or vitamin B6 deficiency or dependency. In the absence of an identifiable cause, therapy should involve an anticonvulsant agent, such as 20 to 40 mg/kg of phenobarbital, 10 to 20 mg/kg of phenytoin, or 0.1 to 0.3 mg/kg of diazepam. Treatment of status epilepticus requires repeated doses of phenobarbital and may require diazepam or midazolam, titrated to clinical signs. The long-term outcome for neonatal seizures usually is related to the underlying cause and to the primary pathology, such as hypoxic-ischemic encephalopathy, meningitis, drug withdrawal, stroke, or hemorrhage.


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Pediatrics_Nelson. Intracranial hemorrhage may be confined to one anatomicarea of the brain, such as the subdural, subarachnoid, periventricular, intraventricular, intraparenchymal, or cerebellar region. Subdural hemorrhages are seen in association with birth trauma, cephalopelvic disproportion,forceps delivery, large for gestational age infants, skull fractures, and postnatal head trauma. The subdural hematomadoes not always cause symptoms immediately after birth;with time, however, the RBCs undergo hemolysis and wateris drawn into the hemorrhage because of the high oncoticpressure of protein, resulting in an expanding symptomaticlesion. Anemia, vomiting, seizures, and macrocephaly mayoccur in an infant who is 1 to 2 months of age and has asubdural hematoma. Child abuse in this situation should be suspected and appropriate diagnostic evaluation undertaken to identify other possible signs of skeletal, ocular, or soft tissue injury. Occasionally, a massive subdural hemorrhage in the neonatal period is


Pediatrics_Nelson

Pediatrics_Nelson. and appropriate diagnostic evaluation undertaken to identify other possible signs of skeletal, ocular, or soft tissue injury. Occasionally, a massive subdural hemorrhage in the neonatal period is caused by rupture of thevein of Galen or by an inherited coagulation disorder, suchas hemophilia. Infants with these conditions exhibit shock,seizures, and coma. The treatment of all symptomatic subdural hematomas is surgical evacuation.


Pediatrics_Nelson

Pediatrics_Nelson. Subarachnoid hemorrhages may be spontaneous, associated with hypoxia, or caused by bleeding from a cerebral arteriovenous malformation. Seizures are a common presenting manifestation, and the prognosis depends on the underlying injury. Treatment is directed at the seizure and the rare occurrence of posthemorrhagic hydrocephalus.


Pediatrics_Nelson

Pediatrics_Nelson. Periventricular hemorrhage and IVH are common in very low birth weight infants; the risk decreases with increasing gestational age. Fifty percent of infants weighing less than 1500 g have evidence of intracranial bleeding.The pathogenesis for these hemorrhages is unknown (theyusually are not caused by coagulation disorders), but theinitial site of bleeding may be the weak blood vessels in theperiventricular germinal matrix. The vessels in this areahave poor structural support. These vessels may rupture and hemorrhage because of passive changes in cerebralblood flow occurring with the variations of blood pressurethat sick premature infants often exhibit (failure of autoregulation). In some sick infants, these blood pressure variations are the only identifiable etiologic factors. In others,the disorders that may cause the elevation or depression ofblood pressure or that interfere with venous return fromthe head (venous stasis) increase the risk of IVH; these disorders include asphyxia,


Pediatrics_Nelson

Pediatrics_Nelson. disorders that may cause the elevation or depression ofblood pressure or that interfere with venous return fromthe head (venous stasis) increase the risk of IVH; these disorders include asphyxia, pneumothorax, mechanical ventilation, hypercapnia, hypoxemia, prolonged labor, breechdelivery, patent ductus arteriosus, heart failure, and therapywith hypertonic solutions such as sodium bicarbonate.


Pediatrics_Nelson

Pediatrics_Nelson. Most periventricular hemorrhages and IVHs occur in the first 3 days of life. It is unusual for IVH to occur after day 5 of life. The clinical manifestations of IVH include seizures, apnea, bradycardia, lethargy, coma, hypotension, metabolic acidosis, anemia not corrected by blood transfusion, bulging fontanelle, and cutaneous mottling. Many infants with small hemorrhages (grade 1 or 2) are asymptomatic; infants with larger hemorrhages (grade 4) often have a catastrophic event that rapidly progresses to shock and coma.


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Pediatrics_Nelson. The diagnosis of IVH is confirmed and the severity gradedby ultrasound through the anterior fontanelle or computedtomography examination. Grade 1 IVH is confined to thegerminal matrix; grade 2 is an extension of grade 1, withblood noted in the ventricle without ventricular enlargement; grade 3 is an extension of grade 2 with ventricular dilation; and grade 4 has blood in dilated ventricles and in thecerebral cortex, either contiguous with or distant from theventricle. Grade 4 hemorrhage has a poor prognosis, as doesthe development of periventricular, small, echolucent cysticlesions, with or without porencephalic cysts and posthemorrhagic hydrocephalus. Periventricular cysts often are notedafter the resolution of echodense areas in the periventricularwhite matter. The cysts may correspond to the developmentof periventricular leukomalacia, which may be a precursorto cerebral palsy. Extensive intraparenchymal echodensitiesrepresent hemorrhagic necrosis. They are associated witha high


Pediatrics_Nelson

Pediatrics_Nelson. to the developmentof periventricular leukomalacia, which may be a precursorto cerebral palsy. Extensive intraparenchymal echodensitiesrepresent hemorrhagic necrosis. They are associated witha high mortality rate and have a poor neurodevelopmentalprognosis for survivors.


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Pediatrics_Nelson. Treatment of an acute hemorrhage involves standard supportive care, including ventilation for apnea and blood transfusion for hemorrhagic shock. Posthemorrhagic hydrocephalus may be managed with serial daily lumbar punctures, an external ventriculostomy tube, or a permanent ventricular-peritoneal shunt. Implementation of the shunt often is delayed because of the high protein content of the hemorrhagic ventricular fluid.


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Pediatrics_Nelson. Conditions known to reduce uteroplacental blood flow or to interfere with spontaneous respiration lead to perinatal hypoxia, lactic acidosis, and, if severe enough to reduce cardiac output or cause cardiac arrest, ischemia. The combination of the reduced availability of oxygen for the brain resulting from hypoxia and the diminished or absent blood flow to the brain resulting from ischemia leads to reduced glucose for metabolism and to an accumulation of lactate that produces local tissue acidosis. After reperfusion, hypoxic-ischemic injury also may be complicated by cell necrosis and vascular endothelial edema, reducing blood flow distal to the Pupils Mydriasis Miosis Unequal, poor light reflex Electroencephalography Normal Low voltage changing to seizure Burst suppression to isoelectric activity Duration >24 h if progresses, otherwise may 24 h to 14 days Days to weeks remain normal


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Pediatrics_Nelson. Electroencephalography Normal Low voltage changing to seizure Burst suppression to isoelectric activity Duration >24 h if progresses, otherwise may 24 h to 14 days Days to weeks remain normal Modified from Sarnat HB, Sarnat MS: Neonatal encephalopathy following fetal distress, Arch Neurol 33:696, 1976. involved vessel. Typically, hypoxic-ischemic encephalopathy in the term infant is characterized by cerebral edema, cortical necrosis, and involvement of the basal ganglia, whereas in the preterm infant it is characterized by periventricular leukomalacia. Both lesions may result in cortical atrophy, mental retardation, and spastic quadriplegia or diplegia.


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Pediatrics_Nelson. The clinical manifestations and characteristic course of hypoxic-ischemic encephalopathy vary according to the severity of the injury (Table 64-2). Infants with severe stage 3 hypoxic-ischemic encephalopathy are usually hypotonic, although occasionally they initially appear hypertonic and hyperalert at birth. As cerebral edema develops, brain functions are affected in a descending order; cortical depression produces coma, and brainstem depression results in apnea. As cerebral edema progresses, refractory seizures begin 12 to 24 hours after birth. Concurrently the infant has no signs of spontaneous respirations, is hypotonic, and has diminished or absent deep tendon reflexes.


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Pediatrics_Nelson. Survivors of stage 3 hypoxic-ischemic encephalopathy have ahigh incidence of seizures and serious neurodevelopmental handicaps. The prognosis of severe asphyxia also depends on otherorgan system injury (see Table 58-6). Another indicator of poorprognosis is time of onset of spontaneous respiration as estimatedby Apgar score. Infants with Apgar scores of 0 to 3 at 10 minuteshave a 20% mortality and a 5% incidence of cerebral palsy; if thescore remains this low by 20 minutes, the mortality increases to60%, and the incidence of cerebral palsy increases to 57%.


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Pediatrics_Nelson. Systemic and local infections (lung, cutaneous, ocular, umbilical, kidney, bone-joint, and meningeal) are common in the newborn period. Infection may be acquired in utero through the transplacental or transcervical routes and during or after birth. Ascending infection through the cervix, with or without rupture of the amniotic fluid membranes, may result in amnionitis, funisitis (infection of the umbilical cord), congenital pneumonia, and sepsis. The bacteria responsible for ascending infection of the fetus are common bacterial organisms of the maternal genitourinary tract, such as group B streptococci, Escherichia coli, Haemophilus influenzae, and Klebsiella. Herpes simplex virus (HSV)-1 or, more often, HSV-2 also causes ascending infection that at times may be indistinguishable from bacterial sepsis. Syphilis and Listeria monocytogenes are acquired by transplacental infection.


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Pediatrics_Nelson. Maternal humoral immunity may protect the fetus against some neonatal pathogens, such as group B streptococci and HSV. Nonetheless, various deficiencies of the neonatal antimicrobial defense mechanism probably are more important than maternal immune status as a contributing factor for neonatal infection, especially in the low birth weight infant. The incidence of sepsis is approximately 1:1500 in full-term infants and 1:250 in preterm infants. The sixfold-higher rate of sepsis in preterm infants relates to the more immature immunologic systems of preterm infants and to their prolonged periods of hospitalization, which increase risk of nosocomially acquired infectious diseases.


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Pediatrics_Nelson. Preterm infants before 32 weeks of gestational age have notreceived the full complement of maternal antibodies (IgG),which cross the placenta by active transport predominantly inthe latter half of the third trimester. In addition, although lowbirth weight infants may generate IgM antibodies, their ownIgG response to infection is reduced. These infants also havedeficiencies of the alternate and, to a smaller degree, the classiccomplement activation pathways, which results in diminishedcomplement-mediated opsonization. Newborn infants alsoshow a deficit in phagocytic migration to the site of infection (tothe lung) and in the bone marrow reserve pool of leukocytes.In addition, in the presence of suboptimal activation of complement, neonatal neutrophils ingest and kill bacteria less effectively than adult neutrophils do. Neutrophils from sick infants seem to have an even greater deficit in bacterial killing capacitycompared with phagocytic cells from normal neonates.


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Pediatrics_Nelson. Defense mechanisms against viral pathogens also may be deficient in a newborn. Neonatal antibody-dependent, cell-mediated immunity by the natural killer lymphocytes is deficient in the absence of maternal antibodies and in the presence of reduced interferon production; reduced antibody levels occur in premature infants and in infants born during a primary viral infection of the mother, such as with enteroviruses, HSV-2, or cytomegalovirus. In addition, antibody-independent cytotoxicity may be reduced in lymphocytes of newborns. Bacterial sepsis and meningitis often are linked closely in neonates. Despite this association, the incidence of meningitis relative to neonatal sepsis has been on a steady decline. The incidence of meningitis is approximately 1 in 20 cases of sepsis. The causative organisms isolated most frequently are the same as for neonatal sepsis: group B streptococci, E. coli, and


Pediatrics_Nelson

Pediatrics_Nelson. L. monocytogenes. Gram-negative organisms, such as Klebsiella, Salmonella, and Serratia marcescens, are more common in less developed countries, and coagulase-negative staphylococcus needs to be considered in very low birth weight infants. Male infants seem to be more susceptible to neonatal infection than female infants. Severely premature infants are at even greater risk secondary to less effective defense mechanisms and deficient transfer of antibodies from the mother to the fetus (which occurs mostly after 32 weeks’ gestation). Neonates in the neonatal intensive care unit live in a hostile environment, with exposure to endotracheal tubes, central arterial and venous catheters, and blood draws, all predisposing to bacteremia and meningitis. Genetic factors have been implicated in the ability of bacteria to cross the blood-brain barrier. This penetration has been noted for group B streptococci, E. coli, Listeria, Citrobacter, and Streptococcus pneumoniae.


Pediatrics_Nelson

Pediatrics_Nelson. Neonatal sepsis presents during three periods. Early-onset sepsis often begins in utero and usually is a result of infection caused by the bacteria in the mother’s genitourinary tract. Organisms related to this sepsis include group B streptococci, E. coli, Klebsiella, L. monocytogenes, and nontypeable H. influenzae. Most infected infants are premature and show nonspecific cardiorespiratory signs, such as grunting, tachypnea, and cyanosis at birth. Risk factors for early-onset sepsis include vaginal colonization with group B streptococci, prolonged rupture of the membranes (>24 hours), amnionitis, maternal fever or leukocytosis, fetal tachycardia, and preterm birth. African American race and male sex are unexplained additional risk factors for neonatal sepsis.


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Pediatrics_Nelson. Early-onset sepsis (birth to 7 days) is an overwhelming multiorgan system disease frequently manifested as respiratory failure, shock, meningitis (in 30% of cases), disseminated intravascular coagulation, acute tubular necrosis, and symmetrical peripheral gangrene. Early manifestations—grunting, poor feeding, pallor, apnea, lethargy, hypothermia, or an abnormal cry—may be nonspecific. Profound neutropenia, hypoxia, and hypotension may be refractory to treatment with broad-spectrum antibiotics, mechanical ventilation, and vasopressors such as dopamine and dobutamine. In the initial stages of early-onset septicemia in a preterm infant, it is often difficult to differentiate sepsis from respiratory distress syndrome. Because of this difficulty, premature infants with respiratory distress syndrome receive broad-spectrum antibiotics.


Pediatrics_Nelson

Pediatrics_Nelson. The clinical manifestations of sepsis are difficult to separate from the manifestations of meningitis in the neonate. Infants with early-onset sepsis should be evaluated by blood and cerebrospinal fluid (CSF) cultures, CSF Gram stain, cell count, and protein and glucose levels. Normal newborns generally have an elevated CSF protein content (100 to 150 mg/dL) and may have 25 to 30/mm3 white blood cells (mean, 9/mm3), which are 75% lymphocytes in the absence of infection. Some infants with neonatal meningitis caused by group B streptococci do not have an elevated CSF leukocyte count but are seen to have microorganisms in the CSF on Gram stain. In addition to culture, other methods of identifying the pathogenic bacteria are the determination of bacterial antigen in samples of blood, urine, or CSF. In cases of neonatal meningitis, the ratio of CSF glucose to blood glucose usually is less than 50%. The polymerase chain reaction test primarily is used to identify viral infections. Serial


Pediatrics_Nelson

Pediatrics_Nelson. or CSF. In cases of neonatal meningitis, the ratio of CSF glucose to blood glucose usually is less than 50%. The polymerase chain reaction test primarily is used to identify viral infections. Serial complete blood counts should be performed to identify neutropenia, an increased number of immature neutrophils (bands), and thrombocytopenia. C-reactive protein levels are often elevated in neonatal patients with bacterial sepsis.


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Pediatrics_Nelson. A chest radiograph also should be obtained to determine the presence of pneumonia. In addition to the traditional neonatal pathogens, pneumonia in very low birth weight infants may be the result of acquisition of maternal genital mycoplasmal agent (e.g., Ureaplasma urealyticum or Mycoplasma hominis).Arterial blood gases should be monitored to detect hypoxemia and metabolic acidosis that may be caused by hypoxia, shock, or both. Blood pressure, urine output, and peripheral perfusion should be monitored to determine the need to treat septic shock with fluids and vasopressor agents.


Pediatrics_Nelson

Pediatrics_Nelson. The mainstay of treatment for sepsis and meningitis is antibiotic therapy. Antibiotics are used to suppress bacterial growth, allowing the infant’s defense mechanisms time to respond. In addition, support measures, such as assisted ventilation and cardiovascular support, are equally important to the management of the infant. A combination of ampicillin and an aminoglycoside (usually gentamicin) for 10 to 14 days is effective treatment against most organisms responsible for early-onset sepsis. The combination of ampicillin and cefotaxime also is proposed as an alternative method of treatment. If meningitis is present, the treatment should be extended to 21 days or 14 days after a negative result from a CSF culture. Persistently positive results from CSF cultures are common with neonatal meningitis caused by gram-negative organisms, even with appropriate antibiotic treatment, and may be present for 2 to 3 days after antibiotic therapy. If gram-negative meningitis is present, some


Pediatrics_Nelson

Pediatrics_Nelson. meningitis caused by gram-negative organisms, even with appropriate antibiotic treatment, and may be present for 2 to 3 days after antibiotic therapy. If gram-negative meningitis is present, some authorities continue to treat with an effective penicillin derivative combined with an aminoglycoside, whereas most change to a third-generation cephalosporin. High-dose penicillin (250,000 to 450,000 U/kg/24 hr) is appropriate for group B streptococcal meningitis. Inhaled nitric oxide, extracorporeal membrane oxygenation (in term infants), or both may improve the outcome of sepsis-related pulmonary hypertension. Intratracheal surfactant may reverse respiratory failure. Intrapartum penicillin empirical prophylaxis for group B streptococcal colonized mothers or mothers with risk factors (fever, preterm labor, previous infant with group B streptococci, and amnionitis) has reduced the rate of early-onset infection.


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Pediatrics_Nelson. Late-onset sepsis (8 to 28 days) usually occurs in a healthy full-term infant who was discharged in good health from the normal newborn nursery. Clinical manifestations may include lethargy, poor feeding, hypotonia, apathy, seizures, bulging fontanelle, fever, and direct-reacting hyperbilirubinemia. In addition to bacteremia, hematogenous seeding may result in focal infections, such as meningitis (in 75% of cases), osteomyelitis (group B streptococci, Staphylococcus aureus), arthritis (gonococcus, S. aureus, Candida albicans, gram-negative bacteria), and urinary tract infection (gram-negative bacteria).


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Pediatrics_Nelson. The evaluation of infants with late-onset sepsis is similar to that for infants with early-onset sepsis, with special attention given to a careful physical examination of the bones (infants with osteomyelitis may exhibit pseudoparalysis) and to the laboratory examination and culture of urine obtained by sterile suprapubic aspiration or urethral catheterization. Late-onset sepsis may be caused by the same pathogens as early-onset sepsis, but infants exhibiting sepsis late in the neonatal period also may have infections caused by the pathogens usually found in older infants (H. influenzae, S. pneumoniae, and Neisseria meningitidis). In addition, viral agents (HSV, cytomegalovirus, or enteroviruses) may manifest with a late-onset, sepsis-like picture.


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Pediatrics_Nelson. Because of the increased rate of resistance of H. influenzae and pneumococcus to ampicillin, some centers begin treatment withampicillin and a third-generation cephalosporin (and vancomycin if meningitis is present) when sepsis occurs in the last week ofthe first month of life. The treatment of late-onset neonatal sepsisand meningitis is the same as that for early-onset sepsis.


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Pediatrics_Nelson. An infection acquired transplacentally during gestation is a congenital infection. Numerous pathogens that produce mild or subclinical disease in older infants and children can cause severe disease in neonates who acquire such infections prenatally or perinatally. Sepsis, meningitis, pneumonia, and other infections caused by numerous perinatally acquired pathogens are the cause of significant neonatal morbidity and mortality. Congenital infections include a well-known group of fungal, bacterial, and viral pathogens: toxoplasmosis, rubella, cytomegalovirus (CMV), herpes simplex virus (HSV), varicella-zoster virus, congenital syphilis, parvovirus, human immunodeficiency virus (HIV), hepatitis B, Neisseria gonorrhoeae, Chlamydia, and Mycobacterium tuberculosis.


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Pediatrics_Nelson. Many of the clinical manifestations of congenital infections aresimilar, including intrauterine growth restriction, nonimmunehydrops, anemia, thrombocytopenia, jaundice, hepatosplenomegaly, chorioretinitis, and congenital malformations. Some unique manifestations and epidemiologic characteristics of theseinfections are listed in Table 66-1. Evaluation of patients thoughtto have a congenital infection should include attempts to isolatethe organism by culture (for rubella, CMV, HSV, gonorrhea, and M. tuberculosis), to identify the antigen of the pathogen (for hepatitis B and Chlamydia trachomatis), to identify the pathogen’sgenome with polymerase chain reaction (PCR), and to identifyspecific fetal production of antibodies (IgM or increasing titer ofIgG for Toxoplasma, syphilis, parvovirus, HIV, or Borrelia).


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Pediatrics_Nelson. Treatment is not always available, specific, or effective. Nonetheless, some encouraging results have been reported for preventing the disease and for specifically treating the infant when the correct diagnosis is made (see Table 66-1). Available @ StudentConsult.com Abnormal Head Size, Shape, and Fontanels Visual Impairment and Leukocoria Petechiae/Purpura


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Pediatrics_Nelson. Available @ StudentConsult.com Abnormal Head Size, Shape, and Fontanels Visual Impairment and Leukocoria Petechiae/Purpura Vertical transmission of Toxoplasma gondii occurs by trans-placental transfer of the organism from the mother to the fetus after an acute maternal infection. Fetal infection rarely can occur after reactivation of disease in an immunocompromised pregnant mother. Transmission from an acutely infected mother to her fetus occurs in about 30% to 40% of cases, but the rate varies directly with gestational age. Transmission rates and the timing of fetal infection correlate directly with placental blood flow; the risk of infection increases throughout gestation to 90% or greater near term, and the time interval between maternal and fetal infection decreases.


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Pediatrics_Nelson. The severity of fetal disease varies inversely with the gestational age at which maternal infection occurs. Most infants have subclinical infection with no overt disease at birth; however, specific ophthalmologic and central nervous system (CNS) evaluations may reveal abnormalities. The classic findings of hydrocephalus, chorioretinitis, and intracerebral calcifications suggest the diagnosis of congenital toxoplasmosis. Affected infants tend to be small for gestational age, develop early-onset jaundice, have hepatosplenomegaly, and present with a generalized maculopapular rash. Seizures are common, and skull films may reveal diffuse cortical calcifications in contrast to the periventricular pattern observed with CMV. These infants are at increased risk for long-term neurologic and neurodevelopmental complications.


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Pediatrics_Nelson. Serologic tests are the primary means of diagnosis. IgG-specific antibodies achieve a peak concentration 1 to 2 months after infection and remain positive indefinitely. For infants with seroconversion or a fourfold increase in IgG titers, specific IgM antibody determinations should be performed to confirm disease. Especially for congenital infections, measurement of IgA and IgE antibodies can be useful to confirm the disease. Thorough ophthalmologic, auditory, and neurologic evaluations (head computed tomography and cerebrospinal fluid [CSF] examination) are indicated. For symptomatic and asymptomatic congenital infections, initial therapy should include pyrimethamine (supplemented with folic acid) combined with sulfadiazine. Duration of therapy is often prolonged, even up to 1 year. Optimal dosages of medications and duration of therapy should be determined in consultation with appropriate specialists. Available @ StudentConsult.com Abnormal Head Size, Shape, and


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Pediatrics_Nelson. Available @ StudentConsult.com Abnormal Head Size, Shape, and Toxoplasma gondii Heterophil-negative mononucleosis Hydrocephalus, abnormal spinal fluid, intracranial Exposure to cats or raw meat or calcifications, chorioretinitis, jaundice, hepatosplenomegaly, immunosuppression fever High-risk exposure at 10–24 wk gestation Many infants asymptomatic at birth Treatment: pyrimethamine plus sulfadiazine Rubella virus Unimmunized seronegative mother; fever ± rash Detectable defects with infection: by 8 wk, 85% 9–12 wk, 50% 13–20 wk, 16% Virus may be present in infant’s throat for 1 yr Prevention: vaccine Intrauterine growth restriction, microcephaly, microphthalmia, cataracts, glaucoma, “salt and pepper” chorioretinitis, hepatosplenomegaly, jaundice, PDA, deafness, blueberry muffin rash, anemia, thrombocytopenia, leukopenia, metaphyseal lucencies, B-cell and T-cell deficiency Infant may be asymptomatic at birth


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Pediatrics_Nelson. CMV Sexually transmitted disease: primary genital infection may be asymptomatic Heterophil-negative mononucleosis; infant may have viruria for 1–6 yr Sepsis, intrauterine growth restriction, chorioretinitis, microcephaly, periventricular calcifications, blueberry muffin rash, anemia, thrombocytopenia, neutropenia, hepatosplenomegaly, jaundice, deafness, pneumonia Many asymptomatic at birth Prevention: CMV-negative blood products Possible treatment: ganciclovir (syphilis) asymptomatic: painless “hidden” chancre Penicillin, not erythromycin, prevents fetal infection Presentation at birth as nonimmune hydrops, prematurity, anemia, neutropenia, thrombocytopenia, pneumonia, hepatosplenomegaly Late neonatal as snuffles (rhinitis), rash, hepatosplenomegaly, condylomata lata, metaphysitis, cerebrospinal fluid pleocytosis, keratitis, periosteal new bone, lymphocytosis, hepatitis Late onset: teeth, eye, bone, skin, central nervous system, ear Treatment: penicillin


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Pediatrics_Nelson. Parvovirus Etiology of fifth disease; fever, rash, arthralgia in Nonimmune hydrops, fetal anemia adults Treatment: in utero transfusion Trypanosoma cruzi Central South American native, immigrant, travel Failure to thrive, heart failure, achalasia (Chagas disease) Chronic disease in mother Treatment: nifurtimox AZT, Zidovudine (azidothymidine); BCG, bacille Calmette-Guerin; CMV, cytomegalovirus; HBIG, hepatitis B immune globulin; INH, isoniazid; PDA, patent ductus arteriosus; PPD, purified protein derivative; TB, tuberculosis; VZIG, varicella-zoster immune globulin.


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Pediatrics_Nelson. With the widespread use of vaccination, congenital rubella is rare in developed countries. Acquired in utero during early gestation, rubella can cause severe neonatal consequences. The occurrence of congenital defects approaches 85% if infection is acquired during the first 4 weeks of gestation; close to 40% spontaneously abort or are stillborn. If infection occurs during weeks 13 to 16, 35% of infants can have abnormalities. Infection after 4 months’ gestation does not seem to cause disease.


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Pediatrics_Nelson. The most common characteristic abnormalities associated with congenital rubella include ophthalmologic (cataracts, retinopathy, and glaucoma), cardiac (patent ductus arteriosus and peripheral pulmonary artery stenosis), auditory (sensorineural hearing loss), and neurologic (behavioral disorders, meningoencephalitis, and mental retardation) conditions. In addition, infants can present with growth retardation, hepatosplenomegaly, early-onset jaundice, thrombocytopenia, radio-lucent bone disease, and purpuric skin lesions (“blueberry muffin” appearance from dermal erythropoiesis).


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Pediatrics_Nelson. Detection of rubella-specific IgM antibody usually indicates recent infection. Measurement of rubella-specific IgG over several months can be confirmatory. Rubella virus can be isolated from blood, urine, CSF, and throat swab specimens. Infants with congenital rubella are chronically and persistently infected and tend to shed live virus in urine, stools, and respiratory secretions for 1 year. Infants should be isolated while in the hospital and kept away from susceptible pregnant women when sent home. Available @ StudentConsult.com


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Pediatrics_Nelson. CMV is the most common congenital infection and the leading cause of sensorineural hearing loss, mental retardation, retinal disease, and cerebral palsy. Congenital CMV occurs in about 0.5% to 1.5% of births. When primary infection occurs in mothers during a pregnancy, the virus is transmitted to the fetus in approximately 35% of cases. Rates of CMV infection are three to seven times greater in infants born to adolescent mothers compared to others. The risk of transmission of CMV to the fetus is independent of gestational age at the time of maternal infection. The earlier in gestation that the primary maternal infection occurs, the more symptomatic the infant will be at birth. The most common sources of CMV for primary infections occurring in mothers during pregnancy are sexual contacts and contact with young children. It is well known that CMV can be transmitted to the fetus even when maternal infection occurred long before conception. This transmission can occur as the result of


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Pediatrics_Nelson. and contact with young children. It is well known that CMV can be transmitted to the fetus even when maternal infection occurred long before conception. This transmission can occur as the result of virus reactivation, chronic infection, or reinfection with a new strain.


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Pediatrics_Nelson. More than 90% of infants who have congenital CMV infection exhibit no clinical evidence of disease at birth. Approximately 10% of infected infants are small for gestational age and have symptoms at birth. Findings include microcephaly, thrombocytopenia, hepatosplenomegaly, hepatitis, intracranial calcifications, chorioretinitis, and hearing abnormalities. Some infants can present with a blueberry muffin appearance as the result of dermal erythropoiesis. Skull films may reveal periventricular calcifications. An additional 10% of infected infants may not present until later in infancy or early childhood, when they are found to have sensorineural hearing loss and developmental delays. Mortality is 10% to 15% in symptomatic newborns. Perinatal CMV infection acquired during birth or from mother’s milk is not associated with newborn illness or CNS sequelae.


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Pediatrics_Nelson. Congenital CMV infection is diagnosed by detection of virus in the urine or saliva. Detection is often accomplished by traditional virus culture methods but can take several weeks to obtain a result. Rapid culture methods using centrifugation to enhance infectivity and monoclonal antibody to detect early antigens in infected tissue culture can give results in 24 hours. PCR also can be used to detect small amounts of CMV DNA in the urine. Detection of CMV within the first 3 weeks after birth is considered proof of congenital CMV infection. Trial studies in severely symptomatic newborns of the antiviral agent ganciclovir have shown a lack of progression of hearing loss.


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Pediatrics_Nelson. Trial studies in severely symptomatic newborns of the antiviral agent ganciclovir have shown a lack of progression of hearing loss. HSV-2 accounts for 90% of primary genital herpes. About 70% to 85% of neonatal herpes simplex infections are caused by HSV-2. Most commonly, neonatal infections are acquired from the mother shortly before (ascending infection) or during passage through the birth canal at delivery. The incidence of neonatal HSV is estimated to range from 1 in 3000 to 1 in 20,000 live births. Infants with HSV infections are more likely to be born prematurely (40% of affected infants are <36 weeks’ gestation). The risk of infection at delivery in an infant born vaginally to a mother with primary genital herpes is about 33% to 50%. The risk to an infant born to a mother with a reactivated infection is less than 5%. More than 75% of infants who acquire HSV infection are born to mothers who have no previous history or clinical findings consistent with HSV infection.


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Pediatrics_Nelson. Most infants are normal at birth, and symptoms of infection develop at 5 to 10 days of life. Symptoms of neonatal HSV infection include disseminated disease involving multiple organ systems, most notably the liver and lungs; localized infection to the CNS; or localized infection to the skin, eyes, and mouth. Symptoms may overlap, and in many cases of disseminated disease, skin lesions are a late finding. Disseminated infection should be considered in any infant with symptoms of sepsis, liver dysfunction, and negative bacteriologic cultures. HSV infection also should be suspected in any neonate who presents with fever, irritability, abnormal CSF findings, and seizures. Initial symptoms can occur anytime between birth and 4 weeks of age, although disseminated disease usually occurs during the first week of life. HSV infections are often severe, and a delay in treatment can result in significant morbidity and mortality.


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Pediatrics_Nelson. For the diagnosis of neonatal HSV infection, specimens for culture should be obtained from any skin vesicle, nasopharynx, eyes, urine, blood, CSF, stool, or rectum. Positive cultures obtained from these sites more than 48 hours after birth indicate intrapartum exposure. PCR is a sensitive method for detecting HSV DNA in blood, urine, and CSF. Parenteral acyclovir is the treatment of choice for neonatal HSV infections. Acyclovir should be administered to all infants suspected to have infection or diagnosed with HSV. The most benign outcome with regard to morbidity and mortality is observed in infants with disease limited to the skin, eyes, and mouth. Available @ StudentConsult.com Rhinorrhea Abnormal Head Size, Shape, and Fontanels Red Eye Hoarseness Hepatomegaly Hearing Loss Lymphadenopathy


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Pediatrics_Nelson. Available @ StudentConsult.com Rhinorrhea Abnormal Head Size, Shape, and Fontanels Red Eye Hoarseness Hepatomegaly Hearing Loss Lymphadenopathy Congenital syphilis most commonly results from transplacental infection of the fetus, although the fetus can acquire infection by contact with a chancre at birth. In addition, hematogenous infection can occur throughout pregnancy. The longer the time elapsed between the mother’s infection and pregnancy, the less likely she is to transmit the disease to the fetus.


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Pediatrics_Nelson. Intrauterine infection can result in stillbirth, hydrops fetalis, or prematurity. Clinical symptoms vary but include hepatosplenomegaly, snuffles, lymphadenopathy, mucocutaneous lesions, osteochondritis, rash, hemolytic anemia, and thrombocytopenia. Untreated infants, regardless of whether they manifest symptoms at birth, may develop late symptoms, which usually appear after 2 years of age and involve the CNS, bones, joints, teeth, eyes, and skin. Some manifestations of disease may not become apparent until many years after birth, such as interstitial keratitis, eighth cranial nerve deafness, Hutchinson teeth, bowing of the shins, frontal bossing, mulberry molars, saddle nose, rhagades, and Clutton joints. The combination of interstitial keratitis, eighth cranial nerve deafness, and Hutchinson teeth is commonly referred to as the Hutchinson triad (see Table 66-1).


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Pediatrics_Nelson. Many infants are asymptomatic at the time of diagnosis. If untreated, most infants develop symptoms within the first 5 weeks of life. The most striking lesions affect the mucocutaneous tissues and bones. Early signs of infection may be poor feeding and snuffles (syphilitic rhinitis). Snuffles are more severe and persistent than the common cold and are often bloody. A maculopapular desquamative rash develops over the palms and soles and around the mouth and anus. The rash may progress to become vesicular with bullae. Severely ill infants may be born with hydrops and have profound anemia. Severe consolidated pneumonia may be present at birth, and there may be laboratory findings consistent with a glomerulonephritis. CSF evaluation may reveal a pleocytosis and elevated protein. More than 90% of symptomatic infants exhibit radiographic abnormalities of the long bones consistent with osteochondritis and perichondritis.


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Pediatrics_Nelson. No newborn should be discharged from the hospital without knowledge or determination of the mother’s serologic status for syphilis. All infants born to seropositive mothers require a careful examination and a quantitative nontreponemal syphilis test. Dark-field examination of direct fluorescent antibody staining of organisms obtained by scraping a skin or mucous membrane lesion is the quickest and most direct method of diagnosis. More commonly, serologic testing is used. The nontreponemal reaginic antibody assays—the Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin—are helpful as indicators of disease. The test performed on the infant should be the same as that performed on the mother to enable comparison of results. An infant should be evaluated further if the maternal titer has increased fourfold, if the infant’s titer is fourfold greater than the mother’s titer, if the infant is symptomatic, or if the mother has inadequately treated syphilis. A mother


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Pediatrics_Nelson. maternal titer has increased fourfold, if the infant’s titer is fourfold greater than the mother’s titer, if the infant is symptomatic, or if the mother has inadequately treated syphilis. A mother infected later in pregnancy may deliver an infant who is incubating active disease. The mother and infant may have negative serologic testing at birth. When clinical or serologic tests suggest congenital syphilis, CSF should be examined microscopically, and a CSF VDRL test should be performed. An increased CSF white blood cell count and protein concentration suggests neurosyphilis; a positive CSF VDRL is diagnostic.


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Pediatrics_Nelson. Parenteral penicillin is the preferred drug of choice for treatment of syphilis. Penicillin G for 10 to 14 days is the only documented effective therapy for infants who have congenital syphilis and neurosyphilis. Infants should have repeat nontreponemal antibody titers repeated at 3, 6, and 12 months to document falling titers. Infants with neurosyphilis must be followed carefully with serologic testing and CSF determinations every 6 months for at least 3 years or until CSF findings are normal. Available @ StudentConsult.com N. gonorrhoeae infection in a newborn usually involves the eyes (ophthalmia neonatorum). Other sites of infection include scalp abscesses (often associated with fetal monitoring with scalp electrodes), vaginitis, and disseminated disease with bacteremia, arthritis, or meningitis. Transmission to the infant usually occurs during passage through the birth canal when mucous membranes come in contact with infected secretions.


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Pediatrics_Nelson. Infection usually is present within the first 5 days of life and is characterized initially by a clear, watery discharge, which rapidly becomes purulent. There is marked conjunctival hyperemia and chemosis. Infection tends to be bilateral; however, one eye may be clinically worse than the other. Untreated infections can spread to the cornea (keratitis) and anterior chamber of the eye. This extension can result in corneal perforation and blindness.


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Pediatrics_Nelson. Recommended treatment for isolated infection, such as ophthalmia neonatorum, is one intramuscular dose of ceftriaxone. Infants with gonococcal ophthalmia should receive eye irrigations with saline solution at frequent intervals before discharge. Topical antibiotic therapy alone is inadequate and is unnecessary when recommended systemic antimicrobial therapy is given. Infants with gonococcal ophthalmia should be hospitalized and evaluated for disseminated disease (sepsis, arthritis, meningitis). Disseminated disease should be treated with antimicrobial therapy (ceftriaxone or cefotaxime) for 7 days. Cefotaxime can be used in infants with hyperbilirubinemia. If documented, infants with meningitis should be treated for 10 to 14 days.


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Pediatrics_Nelson. Tests for concomitant infection with C. trachomatis, congenital syphilis, and HIV should be performed. Results of the maternal test for hepatitis B surface antigen should be confirmed. Topical prophylaxis with silver nitrate, erythromycin, or tetracycline is recommended for all newborns for the prevention of gonococcal ophthalmia. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com C. trachomatis is the most common reportable sexually transmitted infection, with a high rate of infection among sexually active adolescents and young adults. Prevalence of the organism in pregnant women ranges from 6% to 12% and can be 40% in adolescents. Chlamydia can be transmitted from the genital tract of an infected mother to her newborn. Acquisition occurs in about 50% of infants born vaginally to infected mothers. Transmission also has been reported in some infants delivered by cesarean section with intact membranes. In infected infants, the risk of conjunctivitis is 25% to 50%, and the risk of pneumonia is 5% to 20%. The nasopharynx is the most commonly infected anatomic site.


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Pediatrics_Nelson. Neonatal chlamydial conjunctivitis is characterized by ocular congestion, edema, and discharge developing 5 to 14 days to several weeks after birth and lasting for 1 to 2 weeks. Clinical manifestations vary from mild conjunctivitis to intense inflammation and swelling. Both eyes are almost always involved; however, one eye may appear to be more swollen and infected than the other. The cornea is rarely involved, and preauricular adenopathy is rare. Pneumonia in a young infant can occur between 2 and 19 weeks of age and is characterized by an afebrile illness with a repetitive staccato cough, tachypnea, and rales. Wheezing is uncommon. Hyperinflation with diffuse infiltrates can be seen on chest radiograph. Nasal stuffiness and otitis media can occur.