NEONATOLOGY: MANAGEMENT, PROCEDURES, ON-CALL PROBLEMS, DISEASES, AND DRUGS - part 7 pdf

described. 2. Controversial cocaine associations a. In the neonate, the following have been described: Necrotizing enterocolitis, transient hypertension, and reduced cardiac output (on the first day of life); intracranial hemorrhages and infarcts; seizures; apneic spells; periodic breathing; abnormal electroencephalogram; abnormal brainstem auditory evoked potentials; abnormal response to hypoxia and carbon dioxide; and ileal perforation. These reports were mostly case reports or insufficiently controlled case series with numerous confounding factors (notably, various other perinatal and gestational risk factors, including multiple drug and alcohol usage). There are large case-control studies that have found no association between cocaine exposure and intraventricular hemorrhage. Despite earlier concerns, there does not appear to be an increased risk of SIDS. b. Cocaine has been suggested as a teratogen. Its teratogenic potential is presumed to be due to its vascular effects, although direct toxicity on various cell lines may also play a role. Numerous CNS anomalies as well as cardiovascular abnormalities, limb reduction defects, intestinal atresias, and other malformations have been attributed to cocaine. However, most of these associations were derived from case reports or series or poorly controlled studies, and a detailed examination of the data does not substantiate most of these teratogenic associations. An exception appears to be an increased risk of genitourinary tract defects associated with cocaine exposure during gestation. Moreover, there does not appear to be a dysmorphism recognizable as a "cocaine syndrome." Cocaine is associated with an increased incidence of spontaneous abortion, stillbirth, abruptio placentae, premature labor, and IUGR. 3. Prognosis. By 1 year of age, most infants will have achieved catch-up growth. At 3-4 years, there are problems with expressive and receptive speech, and children are reported to be hyperactive, distractable, and irritable and to have problems socializing. There are, however, very limited data, and many of these problems appear to be related to a deprived environment. A number of studies have found no major differences in intellectual abilities or academic achievement between children exposed to cocaine in utero and controls. Studies have suggested that cognitive deficits may be related to heavy cocaine exposure during gestation and that more sensitive and selective tests are required to detect such differences. These deficits were primarily those of poorer recognition memory and information processing. An intriguing study from Toronto assessed the neurodevelopment of adopted children who had been exposed in utero to cocaine. In a follow-up (14 months to 61/2 years), the cocaine-exposed children caught up with the control subjects in weight and stature but not in head circumference. There were no significant differences between the two groups in global IQ, but the cocaine-exposed children had a lower score in verbal comprehension and expressive language. This is the first study to document measurable adverse outcome from in utero cocaine exposure, independent of postnatal home and environmental confounders; however, the effect of prenatal confounding factors such as alcohol could not be eliminated. More recent studies have sustained the debate as to whether cocaine is a behavioral teratogen. One longitudinal study (Singer et al, 2002) found that cocaine-exposed children had significant cognitive deficits and a doubling of the rate of developmental delay during the first 2 years of life, although there were no effects on motor outcomes. On the other hand, a systematic review (Frank et al, 1996) found that, among children ≤6 years, there is no convincing evidence that prenatal cocaine exposure is associated with specific developmental toxic effects that are different in severity, scope of kind from sequelae of multiple other confounding risk factors (such as tobacco, marijuana, alcohol, and environmental quality). C. Alcohol is probably the foremost drug of abuse today. Ethanol is an anxiolytic-analgesic with a depressant effect on the CNS. Both ethanol and its metabolite, acetaldehyde, are toxic. Alcohol crosses the placenta and also impairs its function. The risk of affecting the fetus is related to alcohol dose, but there is a continuum of effects and no known safe limit. The risk that an alcoholic woman will have a child with fetal alcohol syndrome (FAS) is ~35-40%. However, even in the absence of FAS, and also with lower alcohol intakes, there is an increased risk of congenital anomalies and impaired intellect. It is estimated that alcohol is the major cause of congenital mental retardation today. FAS consists of • Prenatal or postnatal growth retardation, CNS involvement such as irritability in infancy or hyperactivity in childhood, developmental delay, hypotonia, or intellectual impairment • Facial dysmorphology: microcephaly, microphthalmos, or short palpebral fissures, a poorly developed philtrum, a thin upper lip (vermilion border), and hypoplastic maxilla. Numerous congenital anomalies have been described after exposure to alcohol in utero both with and without a full-blown FAS. CNS symptoms may appear within 24 h after delivery and include tremors, irritability, hypertonicity, twitching, hyperventilation, hyperacusis, opisthotonos, and seizures. Symptoms may be severe but are usually of short duration. Abdominal distention and vomiting are less frequent than with most other drugs of abuse. In premature infants of women who were heavy alcohol users (>7 drinks/week), there is an increased risk of both intracranial hemorrhage and white matter CNS damage. D. Barbiturates. Symptoms and signs of withdrawal are similar to those observed in narcotic- exposed infants, but symptoms usually appear later. Most infants become symptomatic toward the end of the first week of life, although onset may be delayed up to 2 weeks. The duration of symptoms is usually 2-6 weeks. E. Benzodiazepines. Symptoms are indistinguishable from those of narcotic withdrawal, including seizures. The onset of symptoms may be shortly after birth. F. Phencyclidine (PCP). Symptoms usually begin within 24 h of birth, and the infant may show signs of CNS "hyperirritability" as in narcotic withdrawal. Gastrointestinal symptoms of withdrawal are less common. Very few studies have been done, but at 2 years of age these infants appear to have lower scores in fine motor, adaptive, and language areas of development. Although weight, length, and head circumference are somewhat reduced at birth, most children demonstrate adequate catch-up growth. G. Marijuana. Studies have suggested a slightly shorter duration of gestation and somewhat reduced birth weight, but the extent of these differences was of no clinical importance. Although the drug may have some mild effect on a variety of newborn neurobehavioral traits, there is no evidence of long-term dysfunction. XI. Treatment. Manifestations of drug withdrawal in many infants will resolve within a few days, and drug therapy is not required. Supportive care will suffice in many, if not most, infants. It is not appropriate to treat prophylactically infants of drug-dependent mothers. The infant's withdrawal score should be assessed to monitor the progression of symptoms and the adequacy of treatment. A. Supportive care 1. Minimal stimulation. Attempt to keep the infant in a darkened, quiet environment. Reduce other noxious stimuli. 2. Swaddling and positioning. Use gentle swaddling with positioning that encourages flexion rather than extension. 3. Prevent excessive crying with a pacifier, cuddling, and so on. Feedings should be on demand if possible, and treatment should be individualized based on the infant's level of tolerance. B. Drug treatment. The general aim of treatment is to allow sleep and feeding patterns to be as close to normal as possible. When supportive care is insufficient to do this, or if symptoms are particularly severe, drugs are used. Indications for drug treatment are progressive irritability, continued feeding difficulty, and significant weight loss. A score >7 on the Finnegan score for three consecutive scorings (done every 2-4 h during the first 2 days) may also be regarded as an indication for treatment. However, the Finnegan score should not be followed slavishly and treated as a definitive laboratory value (eg, this is not like treating diabetes by monitoring blood and urine sugar levels). Many centers use the Finnegan score only every 12 h and increase the frequency of its application if the infant's scores rapidly escalate. Drugs used for withdrawal are discussed next. Additional treatment may be required for some symptoms (eg, dehydration or convulsions). With the exception of a few small trials comparing paregoric to phenobarbital for narcotic withdrawal, drug therapy is based largely on anecdotal evidence and hence is variable. 1. Paregoric (camphorated opium tincture). This has 0.4 mg/mL morphine equivalent and is thought to be more "physiologic" than nonnarcotic agents. Treated infants have a more physiologic sucking pattern, a higher calorie intake, and better weight gain than those treated with phenobarbital. Paregoric controls seizures related to narcotic withdrawal better than phenobarbital. It will control symptoms in >90% of infants with withdrawal after narcotic exposure. Potential disadvantages are due to other constituents present in the preparation: Camphor is a CNS stimulant, and paregoric also contains alcohol, anise oil, and benzoic acid, a metabolite of benzyl alcohol. In full-term infants, start with 0.2 mL every 3-4 h; if no improvement is seen within 4 h, increase the dose by 0.05- mL steps up to a maximum of 0.5 mL every 3-4 h. In premature infants, start 0.05 mL/kg every 4 h and increase with increments of 0.02 mL/kg every 4 h until symptoms are controlled, up to a maximum of 0.15 mL/kg every 4 h. Once the withdrawal score is stable for 48 h, the dosage may be tapered by 10% each day. 2. Tincture of opium is similar to paregoric and has the advantage of fewer additives than paregoric. It has 10 mg/mL morphine equivalent and should be diluted to provide the same (morphine) dosage as paregoric. 3. Phenobarbital is an adequate drug for controlling withdrawal from narcotics, especially those of irritability, fussiness, and hyperexcitability. It is not as effective as paregoric for control of gastrointestinal symptoms or seizures after narcotic exposure. It is not suitable for dose titration because of its long half-life. It is mainly useful for treatment of withdrawal from nonnarcotic agents. The dosage is a 20-mg/kg loading dose, followed by 4 mg/kg/day maintenance. Once symptoms have been controlled for 1 week, decrease the daily dose by 25% every week. 4. Chlorpromazine is quite effective in controlling symptoms of withdrawal from both narcotics and nonnarcotics. It has multiple untoward side effects (it reduces seizure threshold, cerebellar dysfunction, and hematologic problems) that make it potentially undesirable for use in neonates when alternatives can be used. The dosage is 3 mg/kg/day, divided into 3-6 doses/day. 5. Clonidine has been used for withdrawal from both narcotic and nonnarcotic agents. The dosage is 3-4 mcg/kg/day, divided into 4 doses/day. 6. Diazepam has been used to treat withdrawal from narcotics. One study showed a greater incidence of seizures after methadone withdrawal when infants were treated with diazepam rather than paregoric. When used to treat methadone withdrawal, it also impairs nutritive sucking more than does methadone alone. It may produce apnea when used with phenobarbital. It may be used for treatment of withdrawal from benzodiazepines and possibly also for the hyperexcitable phase after cocaine exposure. The dosage is 0.5-2 mg every 6-8 h. 7. Combination therapy. Coyle et al (2002) found that the combination of diluted tincture of opium (DTO) in combination with phenobarbital was superior to treatment with DTO alone. Patients given this combination spent less time with severe withdrawal and required less DTO, and duration of hospitalization was reduced by 48%. C. Long-term management. If the infant is discharged after 4 days, an early appointment with the pediatrician should be arranged and the parents should be informed as to possible signs of delayed- onset withdrawal. During the first few years of life, infants exposed to drugs in utero may have various neurobehavioral problems. Minor signs and symptoms of drug withdrawal may continue for a few months after discharge. This places a difficult infant in a difficult home situation. There are a few reports of an increased incidence of child abuse in these circumstances. Thus, frequent follow-up visits and close involvement of social services may be required. XII. Breast-feeding. The various drugs of abuse may be presumed to enter breast milk, and there have been reports of intoxication in breast-fed infants whose mothers had continued to abuse drugs. Mothers on low-dose methadone have been allowed to breast-feed, but this required close supervision and there was a constant concern that unsupervised weaning would precipitate withdrawal. The cautious course would be to dissuade these mothers from breast-feeding unless there is reasonable certainty that they will discontinue their habits. XIII. Warning. Naloxone (Narcan) may precipitate acute drug withdrawal in infants exposed to narcotics. It should not be used in infants born to mothers suspected of abusing opiates. REFERENCES Azuma SD, Chasnoff IJ: Outcome of children prenatally exposed to cocaine and other drugs: a path analysis of three-year data. Pediatrics 1993;92:396. Buehler BA et al: Teratogenic potential of cocaine. Semin Perinatol 1996;20:93. Callahan CM et al: Measurement of gestational cocaine exposure: sensitivity of infants' hair, meconium, and urine. J Pediatr 1992;120:763. Coyle MG et al: Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants. J Pediatr 2002;140:561. Day NL: Research on the effects of prenatal alcohol exposurea new direction. Am J Public Health 1995;85:1614. Dusick AM et al: Risk of intracranial hemorrhage and other adverse outcomes after cocaine exposure in a cohort of 323 very low birth weight infants. J Pediatr 1993;122:438. Frank DA et al: Growth, development, and behavior in early childhood following prenatal cocaine exposure. A systematic review. JAMA 2001;285:1613. Frank DA et al: Maternal cocaine use: impact on child health and development. Curr Probl Pediatr 1996;26:52. Fried PA: Prenatal exposure to tobacco and marijuana: effects during pregnancy, infancy, and early childhood. Clin Obstet Gynecol 1993;36:319. Hawley TL: The development of cocaine-exposed children. Curr Probl Pediatr 1994;24:259. Holzman C et al: Perinatal brain injury in premature infants born to mothers using alcohol in pregnancy. Pediatrics 1995;95:66. Howard BJ, O'Donnell KJ: What is important about a study of within-group differences of 'cocaine babies'? Arch Pediatr Adolesc Med 1995;149:663. Jacobson SW et al: New evidence for neurobehavioral effects of in utero cocaine exposure. J Pediatr 1996;129:581. Kain ZN et al: Cocaine exposure in utero: perinatal development and neonatal manifestationsreview. Clin Toxicol 1992;30:607. King TA et al: Neurologic manifestations of in utero cocaine exposure in near-term and term infants. Pediatrics 1995;96:259. Little BB et al: Is there a cocaine syndrome? Dysmorphic and anthropometric assessment of infants exposed to cocaine. Teratology 1996;54:145. Loebstein R, Koren G: Pregnancy outcome and neurodevelopment of children exposed in utero to psychoactive drugs: the Motherisk experience. J Psychiatry Neurosci 1997;22:192. Lutiger B et al: Relationship between gestational cocaine use and pregnancy outcome: a meta- analysis. Teratology 1991;44:405. Nulman I et al: Neurodevelopment of adopted children exposed in utero to cocaine. Can Med Assoc J 1994;151:1591. Ostrea EM et al: Estimates of illicit drug use during pregnancy by maternal interview, hair analysis, and meconium analysis. J Pediatr 2001;138:344. Ostrea EM et al: Mortality within the first 2 years in infants exposed to cocaine, opiate, or cannabinoid during gestation. Pediatrics 1997;100:79. Pierog S et al: Withdrawal symptoms in infants with the fetal alcohol syndrome. J Pediatr 1977; 90:630. Pietrantoni M, Knuppel RA: Alcohol use in pregnancy. Clin Perinatol 1991;18:93. Richardson GA et al: Prenatal cocaine exposure: effects on the development of school-age children. Neurotoxicol Teratol 1996;18:627. Singer LT et al: Cognitive and motor outcomes of cocaine-exposed infants. JAMA 2002;287: 1952. Slutsker L: Risks associated with cocaine use during pregnancy. Obstet Gynecol 1992;79:778. Stromland K, Hellstrom A: Fetal alcohol syndromean ophthalmological and socioeducational prospective study. Pediatrics 1996;97:845. Theis JGW et al: Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biol Neonate 1997;71:345. Vega WA et al: Prevalence and magnitude of perinatal substance exposure in California. N Engl J Med 1993;329:850. Volpe JJ: Effect of cocaine use on the fetus. N Engl J Med 1992;327:399. CHAPTER 68. Infectious Diseases NOTICE Isolation precautions for all infectious diseases, including maternal and neonatal precautions, breast- feeding, and visiting issues, can be found in Appendix G. NEONATAL SEPSIS I. Definition. Neonatal sepsis is a clinical syndrome of systemic illness accompanied by bacteremia occurring in the first month of life. II. Incidence. The incidence of primary sepsis is 1-8 per 1000 live births and as high as 13-27 per 1000 for infants weighing <1500 g. The mortality rate is high (13-25%); higher rates are seen in premature infants and in those with early fulminant disease. III. Pathophysiology. In considering the pathogenesis of neonatal sepsis, three clinical situations may be defined: early-onset, late-onset, and nosocomial disease. A. Early-onset disease presents in the first 5-7 days of life and is usually a multisystem fulminant illness with prominent respiratory symptoms. Typically, the infant has acquired the organism during the intrapartum period from the maternal genital tract. In this situation, the infant is colonized with the pathogen in the perinatal period. Several infectious agents, notably treponemes, viruses, Listeria, and probably Candida, can be acquired transplacentally via hematogenous routes. Acquisition of other organisms is associated with the birth process. With rupture of membranes, vaginal flora or various bacterial pathogens may ascend to reach the amniotic fluid and the fetus. Chorioamnionitis develops, leading to fetal colonization and infection. Aspiration of infected amniotic fluid by the fetus or neonate may play a role in resultant respiratory symptoms. The presence of vernix or meconium impairs the natural bacteriostatic properties of amniotic fluid. Finally, the infant may be exposed to vaginal flora as it passes through the birth canal. The primary sites of colonization tend to be the skin, nasopharynx, oropharynx, conjunctiva, and umbilical cord. Trauma to these mucosal surfaces may lead to infection. Early-onset disease is characterized by a sudden onset and fulminant course that can progress rapidly to septic shock with a high mortality rate. B. Late-onset disease may occur as early as 5 days of age; however, it is more common after the first week of life. Although these infants may have a history of obstetric complications, these are associated less frequently than with early-onset disease. These infants usually have an identifiable focus, most often meningitis in addition to sepsis. Bacteria responsible for late-onset sepsis and meningitis include those acquired after birth from the maternal genital tract as well as organisms acquired after birth from human contact or from contaminated equipment. Therefore, horizontal transmission appears to play a significant role in late-onset disease. The reasons for delay in development in clinical illness, the predilection for central nervous system (CNS) disease, and the less severe systemic and cardiorespiratory symptoms are unclear. Transfer of maternal antibodies to the mother's own vaginal flora may play a role in determining which exposed infants become infected, especially in the case of group B streptococcal infections. C. Nosocomial sepsis. This form of sepsis occurs in high-risk newborn infants. Its pathogenesis is related to the underlying illness and debilitation of the infant, the flora in the neonatal intensive care (NICU) environment, and invasive monitoring and other techniques used in neonatal intensive care. Breaks in the natural barrier function of the skin and intestine allow this opportunistic organism to overwhelm the neonate. Infants, especially premature infants, have an increased susceptibility to infection because of underlying illnesses and immature immune defenses that are less efficient at localizing and clearing bacterial invasion. D. Causative organisms. The principal pathogens involved in neonatal sepsis have tended to change with time. Primary sepsis must be contrasted with nosocomial sepsis. The agents associated with primary sepsis are usually the vaginal flora. Most centers report group B streptococci (GBS) as the most common, followed by Gram-negative enteric organisms, especially Escherichia coli. Other pathogens include Listeria monocytogenes, Staphylococcus, other streptococci (including the enterococci), anaerobes, and Haemophilus influenzae. In addition, many unusual organisms are documented in primary neonatal sepsis, especially in premature infants. The flora causing nosocomial sepsis vary in each nursery. Staphylococci (especially Staphylococcus epidermidis), gram-negative rods (including Pseudomonas, Klebsiella, Serratia, and Proteus) and fungal organisms predominate. IV. Risk factors A. Prematurity and low birth weight. Prematurity is the single most significant factor correlated with sepsis. The risk increases in proportion to the decrease in birth weight. B. Rupture of membranes. Premature or prolonged (>18 h) rupture of membranes. C. Maternal peripartum fever (≥38 °C/100.4 °F) or infection. Chorioamnionitis, urinary tract infection (UTI), vaginal colonization with GBS, previous delivery of a neonate with GBS disease, perineal colonization with E. coli, and other obstetric complications. D. Amniotic fluid problems. Meconium-stained or foul-smelling, cloudy amniotic fluid. E. Resuscitation at birth. Infants who had fetal distress, were born by traumatic delivery, or were severely depressed at birth and required intubation and resuscitation. F. Multiple gestation. G. Invasive procedures. Invasive monitoring and respiratory or metabolic support. H. Infants with galactosemia (predisposition to E. coli sepsis), immune defects, or asplenia. I. Iron therapy (iron added to serum in vitro enhances the growth of many organisms). J. Other factors. Males are 4 times more affected than females, and the possibility of a sex-linked genetic basis for host susceptibility is postulated. Variations in immune function may play a role. Sepsis is more common in black than in white infants, but this may be explained by a higher incidence of premature rupture of membranes, maternal fever, and low birth weight. Low socioeconomic status is often reported as an additional risk factor, but again this may be explained by low birth weight. NICU staff and family members are often vectors for the spread of microorganisms, primarily as a result of improper hand washing. V. Clinical presentation. The initial diagnosis of sepsis is, by necessity, a clinical one because it is imperative to begin treatment before the results of culture are available. Clinical signs and symptoms of sepsis are nonspecific, and the differential diagnosis is broad, including respiratory distress syndrome (RDS), metabolic diseases, hematologic disease, CNS disease, cardiac disease, and other infectious processes (ie, TORCH infections [see pp 441-442]). Clinical signs and symptoms most often mentioned include the following: A. Temperature irregularity. Hypo- or hyperthermia (greater heat output required by the incubator or radiant warmer to maintain a neutral thermal environment or frequent adjustments of the infant servocontrol probe). B. Change in behavior. Lethargy, irritability, or change in tone. C. Skin. Poor peripheral perfusion, cyanosis, mottling, pallor, petechiae, rashes, sclerema, or jaundice. D. Feeding problems. Feeding intolerance, vomiting, diarrhea (watery loose stool), or abdominal distention with or without visible bowel loops. E. Cardiopulmonary. Tachypnea, respiratory distress (grunting, flaring, and retractions), apnea within the first 24 h of birth or of new onset (especially after 1 week of age), tachycardia, or hypotension, which tends to be a late sign. F. Metabolic. Hypo- or hyperglycemia or metabolic acidosis. VI. Diagnosis A. Laboratory studies 1. Cultures. Blood and other normally sterile body fluids should be obtained for culture. (In neonates <24 h of age, a sterile urine specimen is not necessary, given that the occurrence of UTIs is exceedingly rare in this age group.) Positive bacterial cultures will confirm the diagnosis of sepsis. Computer-assisted, automated blood culture systems have been shown to identify up to 94% of all microorganisms by 48 h of incubation. Results may vary because of a number of factors, including maternal antibiotics administered before birth, organisms that are difficult to grow and isolate (ie, anaerobes), and sampling error with small sample volumes (the optimal amount is 1-2 mL/sample). Therefore, in many clinical situations, infants are treated for "presumed" sepsis despite negative cultures, with apparent clinical benefit. Some controversy currently exists as to whether a spinal tap is needed in asymptomatic newborns being worked up for early-onset presumptive sepsis. Many institutions perform lumbar punctures only on infants who are clinically ill or who have documented positive blood cultures. 2. Gram's stain of various fluids. Gram's staining is especially helpful for the study of CSF. Gram-stained smears and cultures of amniotic fluid or of material obtained by gastric aspiration are often performed. White blood cells in the samples can be maternal in origin, and their presence along with bacteria indicates exposure and possible colonization but not necessarily actual infection. 3. Adjunctive laboratory tests a. White blood cell count with differential. These values alone are very nonspecific. There are references for total white blood cell count and absolute neutrophil count (probably a better measure) as a function of postnatal age in hours (see Chapter 54, particularly Tables 54-1 and 54-2). Neutropenia may be a significant finding with an ominous prognosis when associated with sepsis. The presence of immature forms is more specific but still rather insensitive. Ratios of bands to segmented forms >0.3 and of bands to total polymorphonuclear cells >0.1 have good predictive value, if present. A variety of conditions other than sepsis can alter neutrophil counts and ratios, including maternal hypertension and fever, neonatal asphyxia, meconium aspiration syndrome, and pneumothorax. Serial white blood cell counts several hours apart may be helpful in establishing a trend. b. Platelet count. A decreased platelet count is usually a late sign and is very nonspecific. c. Acute-phase reactants are a complex multifunctional group comprising complement components, coagulation proteins, protease inhibitors, C-reactive protein (CRP), and others that rise in concentration in the serum in response to tissue injury. i. CRP is an acute-phase reactant that increases the most in the presence of inflammation caused by infection or tissue injury. The highest concentrations of CRP have been reported in patients with bacterial infections, whereas moderate elevations typify chronic inflammatory conditions. Synthesis of acute-phase proteins by hepatocytes is modulated by cytokines. Interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor (TNF) are the most important regulators of CRP synthesis. After onset of inflammation, CRP synthesis increases within 4-6 h, doubling every 8 h, and peaks at about 36- 50 h. Levels remain elevated with ongoing inflammation, but with resolution they decline rapidly due to a short half-life of 4-7 h. CRP is, therefore, superior to other acute-phase reactants that rise much slower. CRP demonstrates high sensitivity and negative predictive value. A single normal value cannot rule out infection because the sampling may have preceded the rise in CRP. Serial determinations are, therefore, indicated. CRP elevations in noninfected neonates have been seen with fetal hypoxia, RDS, and meconium aspiration. As well, a false-positive rate of 8% has been found in healthy neonates. Nonetheless, CRP is a valuable adjunct in the diagnosis of sepsis, monitoring the response to treatment, as well as guiding duration of treatment. ii. The standard erythrocyte sedimentation rate may be elevated but usually not until well into the illness and, therefore, is used rather infrequently in the initial workup. iii. Cytokines IL-1β, IL-6, IL-8, and TNF are produced primarily by activated monocytes and macrophages and are major mediators of the systemic response to infection. Studies have shown that combined use of IL-8 and CRP as part of the workup for bacterial infection reduces unnecessary antibiotic treatment. iv. Surface neutrophil CD11 has been shown to be an excellent marker of early infection that correlates well with CRP but peaks earlier. d. Miscellaneous tests. Abnormal values for bilirubin, glucose, and sodium may, in the proper clinical situation, provide supportive evidence for sepsis. [...]...TABLE 6 8-1 HEPATITIS TESTING Specific test HAV Anti-HAV Anti-HAVIgM Anti-HAVIgG HBV HBsAg Anti-HBs HBeAg Anti-HBe HBcAg Anti-HBc Anti-HBcIgM Anti-HBc-IgG HVC Anti-HCV Description Etiologic agent of "infectious" hepatitis Detectable at onset of symptoms; lifetime persistence Indicates recent... developmental quantitative and qualitative neutrophil defects Studies of infected neonates suggest that the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) or recombinant human granulocyte-macrophage colony- stimulating factor (rhGM-CSF) can partially counterbalance these defects and reduce morbidity and mortality Further controlled studies with GCSF and GM-CSF are required Intravenous... testing (see Table 6 8-1 ) 1 Mother Test for HBsAg, HBeAg, anti-HBe, and anti-HBc 2 Infant Test for HBsAg and anti-HBc-IgM Most infants demonstrate antigenemia by 6 months of age, with peak acquisition at 3-4 months Cord blood is not a reliable indicator of neonatal infection (1) because contamination could have occurred with antigen-positive maternal blood or vaginal secretions and (2) because of the... HIV-negative women III Clinical presentation The average incubation period is generally 6 -7 weeks, with a range of 2- 26 weeks Infants with acute hepatitis C typically are asymptomatic or have a mild clinical illness Approximately 6 5 -7 0% of patients experience chronic hepatitis, 20% cirrhosis, and 1-5 % hepatocellular carcinoma IV Diagnosis Detection of antibody to HCV (anti-HCV) in serum using second-generation... bottle- and breast-fed infants Given the efficacy of HBV vaccine with HBIG, even the theoretical risk for transmission through breast-feeding is of little concern, and breast-feeding can be encouraged E Vaccine efficacy The overall protective efficiency rate in neonates given HBV vaccine and HBIG exceeds 93% The HBV-infected neonate is usually asymptomatic but may develop mild clinical hepatitis and. .. vaccine to their routine childhood immunization program by 19 97 Two dose schedules have been proposed; each includes 3 separate doses In option 1, these are at birth, 1-2 months, and at 6-1 8 months; in option 2, doses should be given at 1-2 months, 4 months, and 6-1 8 months Hepatitis C I Definition Hepatitis C virus (HCV) is a single-stranded RNA virus that accounts for 20% of all cases of acute hepatitis... occurs at 1-1 2 weeks, there is an 81% risk of fetal infection; at 1 3-1 6 weeks, 54%; at 1 7- 2 2 weeks, 36%; at 2 3-3 0 weeks, 30%; there is a rise to 60% at 3 1-3 6 weeks; and 100% in the last month of pregnancy No correlation exists between the severity of maternal rubella and teratogenicity However, the incidence of fetal effects is greater the earlier in gestation that infection occurs, especially at 1-1 1 weeks,... documented synergism in vitro E Complications and supportive therapy 1 Respiratory Ensure adequate oxygenation with blood gas monitoring, and initiate O2 therapy or ventilator support if needed 2 Cardiovascular Support blood pressure and perfusion to prevent shock Use volume expanders, 1 0-2 0 mL/kg (normal saline, albumin, and blood), and monitor the intake of fluids and output of urine Pressor agents such... for 4-6 months after infection; detectable in "window" period after surface antigen disappears Appears later and may persist for years if viral replication continues Etiologic agent of hepatitis C Serologic determinant of hepatitis C infection IgM and IgG, Immunoglobulins M and G; HAV, hepatitis A virus; antiHAV, antibody to HAV (IgM and IgG subclasses); anti-HAV-IgM, IgM class antibody to HAV; anti-HAV-IgG,... (CDC) in 1996 and were supported by American Association of Pediatrics and American College of Obstetricians and Gynecologists The guidelines recommended one of two approaches: the prenatal screening approach (screening all pregnant women for GBS infection at 3 5-3 7 weeks' gestation and treatment of those women with positive cultures) and identifying women who present with risk factors and treating them . granulocyte-macrophage colony- stimulating factor (rhGM-CSF) can partially counterbalance these defects and reduce morbidity and mortality. Further controlled studies with G- CSF and GM-CSF are required IL-6, IL-8, and TNF are produced primarily by activated monocytes and macrophages and are major mediators of the systemic response to infection. Studies have shown that combined use of IL-8 and. infection IgM and IgG, Immunoglobulins M and G; HAV, hepatitis A virus; anti- HAV, antibody to HAV (IgM and IgG subclasses); anti-HAV-IgM, IgM class antibody to HAV; anti-HAV-IgG, IgG class antibody to HAV;