The peritoneal cavity may be small because growth has proceeded without the solid organs in proper position. A ruptured omphalocele may be confused with a gastroschisis, but infants with omphalocele do not possess an intact umbilical cord at the level of the abdominal wall. Care of the unprotected intestines is as described for gastroschisis (see previous text). The omphalocele sac conserves heat, prevents evaporative loss, allows effective peristalsis, and must be protected. Timing of surgery is determined by the size of the defect, gestational age, and presence of other congenital anomalies. The application of various topical agents has been described to allow gradual epithelialization of the sac. Staged reduction with a compressive dressing to encourage growth of the abdominal cavity may be appropriate. Persistence of a patent processus vaginalis (related to testicular descent) is responsible for inguinal hernias and hydroceles in the neonate. The opening of the processus at the inguinal ring is large enough to allow abdominal viscera to extrude through the defect with increased intra-abdominal pressure. Peritoneal fluid leaves the abdominal cavity and accumulates in the processus vaginalis. Hydroceles are classified as communicating, if the processus remains patent, and noncommunicating, if the processus obliterates. Inguinal hernias tend to present as bulges at the pubic tubercle that continue along the inguinal canal. Hydroceles are typically are found in the scrotum, transilluminate, and are not reducible. Hydroceles frequently resolve without intervention because the processus vaginalis continues to obliterate after birth. An umbilical hernia is a skin-covered fascial defect at the umbilicus that allows protrusion of intra-abdominal contents. During infancy, surgical intervention for an umbilical hernia is rarely warranted. The natural history is one of gradual closure of the umbilical fascial defect, often leading to complete resolution. Surgical correction should be considered if the defect persists after the second birthday. Because of the esophageal obstruction, the infant is unable to handle secretions, with subsequent "excess salivation" and aspiration of pharyngeal contents. Communication between the tracheobronchial tree and the distal fistula allows the crying newborn to greatly distend the stomach with air. This impairment of diaphragmatic excursion can promote basilar atelectasis and respiratory distress. Typically, the newborn is unable to manage oral secretions and requires frequent suctioning. Attempted feedings result in prompt regurgitation, coughing, choking, and cyanosis. The radiograph should also be examined for skeletal anomalies, pulmonary infiltrates, cardiac size and shape, and abdominal bowel gas patterns. Preoperative treatment should focus on protecting the lungs by evacuating the proximal esophageal pouch with an indwelling Replogle tube or frequent suctioning. Placing the baby in an upright (45-degree) position lessens the likelihood of reflux of gastric contents up the distal esophagus into the trachea.
Indeed, comparative sequence analysis of these proximal enhancers strongly supports the conclusion that both play roles in higher primates but not in other species. Distal Enhancers In addition to the proximal promoters and enhancers, both the -like and -like globin gene clusters are regulated by distal control regions. In both cases, deletion of the distal control region is associated with thalassemia (Figure 3. Addition of the distal control regions has profound effects on expression of linked genes in transgenic mice. This region is highly conserved in mammals, with highly similar sequences indicative of constraint found both in the hypersensitive sites and between them (50, 90). It is about 250 bp in length (99), located in a widely expressed gene called C16orf35 (Figure 3. It is very strongly conserved in mammals, with obvious matches to species as distant as opossum (Figures 3. Functional tests have shown that the homologous regions of chicken and fish also have enhancer activity, despite considerable divergence outside the proteinbinding sites (44). Although expression of the mouse -globin genes is reduced substantially, the locus is not silenced. Thus the repressive heterochromatin seen in the hybrid murine erythroleukemia cells carrying human chromosome 11 with the Hispanic deletion may have been produced during the chromosome transfers between cell lines. However, transgene constructs containing the -globin can still show position effect variegation (104). They also can overcome some but not all repressive effects after integration at a variety of chromosomal locations. All are heterodimers containing a Maf protein as one subunit, which is the basis for the name of the response element. Many of the sites have implicated directly in activity by mutagenesis and gene transfer. The protein binding sites in the distal positive regulators show some common patterns (Figure 3. This appears to be an old transposable element (predating most of the mammalian radiation), but one that continues to provide a regulatory function. Intense study since then has revealed much about their structure, evolution and regulation. However, understanding sufficient to lead to clinical applications continues to elude us. The myriad levels of regulation and function that operate within these gene clusters certainly confound attempts to find simplifying conclusions. Despite these challenges, studies of the globin gene clusters have consistently provided new insights into function, regulation and evolution. The lessons being learned as we try to integrate information from classical molecular biology and genetics, new high throughput biochemical assays, and extensive interspecies sequence comparisons are paving the way for applying these approaches genome-wide. The globin gene clusters illustrate the need to distinguish common from lineage-specific regulation. Although simple generalizations are rare, the extensive information that one needs for interpreting data in the context of comparative genomics is readily accessible. Deeper information on the variants associated with disorders of the hemoglobins can be obtained from HbVar. We hope that the examples presented here will be helpful in guiding interpretation of the multitude of data available to the readers now and in the future. The fusion of two peptide chains in hemoglobin Lepore and its interpretation as a genetic deletion. Localization of the human alpha globin structural gene to chromosome 16 in somatic cell hybrids by molecular hybridization assay. Chromosomal localization of the human beta globin gene to human chromosome 11 in somatic cell hybrids. The structure of the human zeta-globin gene and a closely linked, nearly identical pseudogene. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.
Adverse intrauterine circumstances that overwhelm compensatory mechanisms lead to progressive damage to fetal organs, including the brain, and may result in fetal death. Fetal alcohol and fetal hydantoin syndromes are well defined but often difficult to diagnose in the neonatal period. Infants with intrauterine exposure to opiates, cocaine, alcohol, or some prescription medications may demonstrate neonatal withdrawal syndrome (see Chapter 103). These infants require close observation after delivery and may require medications to help them through the withdrawal period. Infants with central nervous system infarctions resulting from cocaine exposure are at risk for cerebral palsy, especially hemiplegia, as well as cognitive and sensory impairments. The type of fetal distress and, after birth, evidence of neonatal encephalopathy and brain injury on neuroimaging, electroencephalogram, and neurodevelopmental examination (see Chapter 16) are prognostic indicators. Nonetheless, the majority of infants who demonstrate signs of fetal distress do not develop neonatal encephalopathy, persistent pulmonary hypertension, or neurodevelopmental disability. The type of congenital anomaly, its severity, and whether further evaluation has identified other anomalies or etiology, to determine how you should counsel the parents. Mothers who were counseled after prenatal diagnosis of a congenital anomaly reported in an interview a week after delivery that the consultation helped to prepare them. The study concluded that "parents want realistic medical information, specific to their situation, provided in an empathetic manner and want to be allowed to hope for the best possible outcome. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Prenatal consultation with a neonatologist for congenital anomalies: parental perceptions. Intrauterine growth and neuropsychological performance in very low birth weight preschoolers. Cyanosis can be caused by a rise in deoxygenated hemoglobin (more common) or an abnormal hemoglobin disorder. If the infant has increased respiratory effort with increased rate, retractions, and nasal flaring, respiratory disease should be high on the list of differential diagnoses. Cyanotic heart disease usually presents without respiratory symptoms ("happy blue baby") but can have effortless tachypnea (rapid respiratory rate without retractions). A murmur usually implies heart disease, but in infants with congenital heart malformations, <50% have a murmur in the newborn period. Infants with transposition of the great vessels and tricuspid atresia can present almost immediately at birth with cyanosis. In the perinatal period, infants with truncus arteriosus, total anomalous pulmonary venous return, and tetralogy of Fallot can present with cyanosis. Is the cyanosis continuous, intermittent, cyclical, sudden in onset, or occurring only with feeding or crying Intermittent cyanosis is more common with neurologic disorders; these infants may have apneic spells alternating with periods of normal breathing. Cyanosis with feeding can occur with esophageal atresia and severe gastroesophageal reflux. Crying may improve cyanosis in respiratory disease and worsen it in cardiac disease. The pulse oximeter measures oxygen saturation of hemoglobin that is available to bind oxygen. Has the baby had the recommended pulse oximetry screening for congenital heart disease Differential cyanosis is when there is cyanosis of the upper or lower part of the body only, and it usually signifies serious heart disease. To diagnose this, oxygen saturation should be measured in the preductal (right hand is preferred since it accurately reflects preductal value) and postductal (foot). Infection, such as that which can occur with premature rupture of membranes, may cause shock and hypotension with resultant cyanosis.
Cutaneous dissemination occurs in 40% of these pts and increases the risk for other complications (pneumonitis, meningoencephalitis, hepatitis). Prednisone (given along with antiviral therapy at a dosage of 60 mg/d for the first week of zoster, with the dose then tapered by 50% weekly over the next 2 weeks) can accelerate quality-of-life improvements, including a return to usual activity; prednisone treatment is indicated only for healthy elderly persons with moderate or severe pain at presentation. Irrespective of serologic status, pts >60 years old should receive a vaccine with 18 times the viral content of varicella vaccine; zoster vaccine reduces the incidence of zoster and postherpetic neuralgia. The primary adverse events include electrolyte disturbances and renal dysfunction. Influenza A and B viruses are major human pathogens and are morphologically similar; influenza B infection is associated with less severe disease than influenza A infection, and influenza C virus causes subclinical disease. Influenza A epidemics occur almost exclusively during the winter months in temperate climates but occur year-round in the tropics. Chronic cardiopulmonary disease and old age are the most prominent risk factors for severe illness. Clinical Manifestations Influenza has a wide spectrum of clinical presentations, ranging from a mild illness resembling the common cold to severe prostration with relatively few respiratory symptoms. The classic description involves the abrupt onset of headache, fever, chills, myalgia, and malaise in the setting of respiratory symptoms. Pts have progressive pulmonary disease and high titers of virus in respiratory secretions. Laboratory Findings Most commonly, a laboratory diagnosis is made with a rapid test that detects viral antigens from throat swabs, nasopharyngeal washes, or sputum. Prophylaxis Annual vaccination with either an inactivated or a live attenuated vaccine is the main public health measure for prevention of influenza. Chemoprophylaxis can be administered simultaneously with inactivated-but not with live-vaccine. Clinical presentations for viral infections are generally not specific enough to allow an etiologic diagnosis, and viral illnesses are typically grouped into clinical syndromes. This section will cover the six major groups of respiratory viruses; see Table 110-2 for an overview and Chap. Epidemiology Rhinoviruses are spread by direct contact with infected secretions, usually respiratory droplets. Diagnosis An etiologic diagnosis usually is not attempted, given that the disease is generally mild and self-limited. Prevention Monthly administration of palivizumab is approved for prophylaxis in children <2 years of age who have bronchopulmonary dysplasia or cyanotic heart disease or who were born prematurely. Clinical Manifestations Infections are milder among older children and adults, but severe, prolonged, and fatal infection has been reported among pts with severe immunosuppression, including transplant recipients. Transmission takes place primarily from fall to spring via inhalation of aerosolized virus, through inoculation of the conjunctival sacs, and probably via the fecal-oral route. Clinical Manifestations In children, adenovirus causes acute upper and lower respiratory tract infections and outbreaks of pharyngoconjunctival fever (a syndrome of fever, bilateral conjunctivitis, sore throat, and cervical adenopathy typically due to types 3 and 7). In pts who have received a solid-organ transplant, adenovirus can affect the transplanted organ and disseminate to other organs.
Intracranial hemorrhage, whether subarachnoid, periventricular, or intraventricular, may occur as a result of hypoxic insults that can lead to neonatal seizures. In primary subarachnoid hemorrhage, convulsions often occur on the second postnatal day, and the infant appears quite well during the interictal period. Periventricular or intraventricular hemorrhage arising from the subependymal germinal matrix is accompanied by subtle seizures, decerebrate posturing, or generalized tonic seizures, depending on the severity of the hemorrhage. Subdural hemorrhage over the cerebral convexities leads to focal seizures and focal cerebral signs. The duration of hypoglycemia and the time lapse before initiation of treatment determine the occurrence of seizures. Hypernatremia is seen with dehydration as a result of inadequate intake in breast-fed infants, excessive use of sodium bicarbonate, or incorrect dilution of concentrated formula. Infants with this disorder experience intrauterine convulsions and are born with meconium staining. Seizures in infants with amino acid disturbances are invariably accompanied by other neurologic manifestations. Intracranial infection secondary to bacterial or nonbacterial agents may be acquired by the neonate in utero, during delivery, or in the immediate perinatal period. Meningitis resulting from group B Streptococcus, Escherichia coli, or Listeria monocytogenes infection is accompanied by seizures during the first week of life. Nonbacterial causes such as toxoplasmosis and infection with herpes simplex, cytomegalovirus, rubella, and coxsackie B viruses lead to intracranial infection and seizures. Three categories of drugs used by the mother lead to passive addiction and drug withdrawal (sometimes accompanied by seizures) in the infant. These are analgesics such as heroin, methadone, and propoxyphene (Darvon); sedative hypnotics such as secobarbital; and alcohol. Inadvertent injection of local anesthetics into the fetus at the time of delivery (paracervical, pudendal, or saddle block anesthesia) may cause generalized tonic-clonic seizures. It is important to understand that seizures in the neonate are different from those seen in older children. The differences are perhaps due to the neuroanatomic and neurophysiologic developmental status of the newborn infant. In the neonatal brain, glial proliferation, neuronal migration, establishment of axonal and dendritic contacts, and myelin deposition are incomplete. Four types of seizures, based on clinical presentation, are recognized: subtle, clonic, tonic, and myoclonic. Subtle seizures are not clearly clonic, tonic, or myoclonic and are more common in premature than in full-term infants. Subtle seizures are more commonly associated with an electroencephalographic seizure in premature infants than in fullterm infants. They consist of tonic horizontal deviation of the eyes with or without jerking; eyelid blinking or fluttering; sucking, smacking, or drooling; "swimming," "rowing," or "pedaling" movements; and apneic spells. Apnea as a manifestation of seizures is usually accompanied or preceded by other subtle manifestations. Clonic seizures are more common in full-term infants than in premature infants and commonly associated with an electroencephalographic seizure. Well-localized, rhythmic, slow jerking movements involving the face and upper or lower extremities on one side of the body or the neck or trunk on one side of the body. Several body parts seize in a sequential, nonjacksonian fashion (eg, left arm jerking followed by right leg jerking). Sustained posturing of a limb, asymmetric posturing of the trunk or neck, or both. Most commonly, these occur with a tonic extension of both upper and lower extremities (as in decerebrate posturing) but may also present with tonic flexion of the upper extremities with extension of the lower extremities (as in decorticate posturing). Myoclonic seizures are seen in both full-term and premature infants and are characterized by single or multiple synchronous jerks. Typically involve the flexor muscles of an upper extremity and are not commonly associated with electroencephalographic seizure activity. Exhibit asynchronous twitching of several parts of the body and are not commonly associated with electroencephalographic seizure activity.
This test can be positive in the presence of maternal autoimmune hemolytic disease, particularly collagen vascular disease. The reciprocal of the highest dilution of maternal serum that produces agglutination is the indirect antiglobulin titer. Verification of the Rh-negative status at the first prenatal visit may be obtained by the following measures: 1. Once an IgG-Rh antibody has been identified, it is important to determine the titer. Invasive fetal testing becomes indicated when the titer is above a critical level, usually between 1:8 and 1:16. A negative antibody screen (indirect Coombs test) signifies absence of sensitization. To reasonably predict the risk of moderate to severe fetal disease, serial determinations of amniotic fluid bilirubin levels present photometrically at 450 nm are plotted on standard graphs according to gestational age (known as the Liley curve). As a screening study in pregnancies at risk, serial fetal ultrasound examinations allow detection of scalp edema, ascites, or other signs of developing hydrops fetalis. Based on the studies just mentioned, intrauterine transfusion may be indicated because of possible fetal demise or the presence of fetal hydrops. The goal is maintenance of effective erythrocyte mass within the fetal circulation and maintenance of the pregnancy until there is a reasonable chance for successful extrauterine survival of the infant. If premature delivery is anticipated, glucocorticoids should be given to accelerate fetal lung maturation and reduce the risk of intraventricular hemorrhage. Moderately to severely anemic infants with or without hydropic features are at risk for high-output cardiac failure, hypoxemia secondary to decreased oxygen-carrying capacity or surfactant deficiency, and hypoglycemia. These infants may require immediate single-volume exchange blood transfusion at delivery to improve oxygen-carrying capacity, mechanical support of ventilation, and an extended period of monitoring for hypoglycemia. A cord blood bilirubin level >4 mg/dL, a cord hemoglobin <12 g/dL, or both usually suggests moderate to severe disease. The cord blood is used for these and initial screening studies, including blood typing, Rh typing, and Coombs test. Determination of the rate of increase in unconjugated bilirubin levels provides an index of the severity of the hemolytic process and the need for exchange transfusion. In severe Rh hemolytic disease, phototherapy is used only as an adjunct to exchange transfusion. Phototherapy decreases bilirubin levels and reduces the number of total exchange transfusions required. Optimally, exchange transfusion is done well before this exchange level is reached to minimize the risk of entry of unconjugated bilirubin into the central nervous system. Consideration should be given to irradiation of blood before the transfusion is given, particularly in preterm infants or infants expected to require multiple transfusions, to reduce the risk of graft-versus-host disease. A rapid rebound of serum bilirubin is common after reequilibration, and thus additional exchange transfusions may be required. Tin (Sn) porphyrin can decrease the production of bilirubin and reduce the need for exchange transfusion and duration of phototherapy. The amount of fetal blood entering the maternal circulation may be estimated using the Kleihauer-Betke acid elution technique (page 562) during the immediate postpartum period. These antigens, however, are significantly less antigenic than the D antigen, clinical manifestations of incompatibility are frequently milder, and the risk of severe disease is considerably less. Skilled resuscitation and anticipation of selective systemic complications may prevent early neonatal death. Isovolumetric partial exchange transfusion with type O Rh-negative packed erythrocytes.
Hypocalcemia is likely the most common disorder of either Ca+2 or Mg+2 in newborn infants, and it affects both preterm and term infants. In premature infants, it has been shown that tCa+2 levels as low as 6 mg/dL correspond to iCa+2 levels >3 mg/dL. After delivery, this massive supply of Ca+2 is suddenly stopped, and Ca+2 must be given enterally. Despite this drop in supply, full-term infants tolerate the change well and do not become hypocalcemic. Premature (especially <28 weeks) or sick infants often become hypocalcemic during the first 3 days of life. Resuscitation and the use of alkali to correct acidosis (bicarbonate therapy) may have multiple effects resulting in hypocalcemia (eg, lower iCa+2 levels, decreased Ca+2 flux from bones, relative hyperphosphatemia secondary to increased circulating endogenous phosphorous following postasphyxial renal impairment). Additional factors include meconium aspiration syndrome, compromised placental blood flow, sepsis, and shock. Of special note is alkalosis secondary to hyperventilation and hypocarbia postresuscitation. The combination of bicarbonate infusions and hypocarbia can induce an alkalosis with profound hypocalcemia. Related factors that have been identified are increased calcitonin levels, decreased bone Ca+2 flux, hypomagnesemia, hypoparathyroidism, and hyperphosphatemia. Infants unable to take enteral feeds by 3 days of age will need calcium supplementation. Because hypocalcemia is related to hypomagnesemia, both elements require supplementation to prevent secondary suppression of parathormone recurrence of hypocalcemia. May be secondary to maternal gestational magnesium losses or to impaired intestinal uptake. Hypomagnesemia frequently occurs with hypocalcemia and must be looked for in any at-risk infant. The DiGeorge sequence with absence of parathyroid glands and related craniofacial and cardiac anomalies often presents with hypocalcemia. This causes transient hypoparathyroidism in the infant due to fetal parathyroid suppression. Include furosemide-induced hypercalciuria; citrated blood transfusions, which reduce iCa+2 due to a citrate-calcium complex and an alkalosis following metabolism of citrate; and inadequate prenatal vitamin D supplementation of the mother or the infant during the first 6 months of life. Maternal use of anticonvulsants like phenobarbital can cause increased hepatic catabolism of vitamin D, resulting in maternal vitamin D deficiency and subsequent neonatal hypocalcemia. Only an index of suspicion on the basis of risk factors will lead to a correct diagnosis. Imaging studies for bone demineralization, metaphyseal lucencies, and rib and long bone fractures may be helpful for late hypocalcemia. More acutely, the absence of a thymic shadow on chest radiograph will suggest the DiGeorge sequence. Reserved for symptomatic hypocalcemic infants with apneic spells, seizures, or cardiac failure with arrhythmia. For infants with limited enteral intake or who are dependent on parenteral calcium intake, an intravenous dosage of 45 mg/kg/d of elemental calcium with a calcium-phosphate ratio ranging from 1. Parenteral fluids cannot approximate the intrauterine level of Ca+2 intake without some precipitation in solution.
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