Chapter 98 – Clinical Manifestations of Diseases in the Newborn Period
The wide variety of disorders that affect the newborn originate in utero, during birth, or in the immediate postnatal period. These disorders may represent genetic mutations, chromosomal aberrations, or acquired diseases and injuries. Recognizing disease in newborn infants depends on knowledge of the disorder and evaluation of a limited number of relatively nonspecific clinical signs and symptoms.
Central cyanosis has respiratory, cardiac, central nervous system (CNS), hematologic, and metabolic causes ( Table 1 ). Respiratory insufficiency may be due to pulmonary conditions or may be secondary to CNS depression as a result of drugs, intracranial hemorrhage, or anoxia. If caused by the former, respirations tend to be rapid and may be accompanied by retraction of the thoracic cage. If it is due to the latter, respirations tend to be irregular and weak and are often slow. Cyanosis unaccompanied by obvious signs of respiratory difficulty suggests cyanotic congenital heart disease or methemoglobinemia. Cyanosis resulting from congenital heart disease may, however, be difficult to distinguish clinically from cyanosis caused by respiratory disease. Episodes of cyanosis may also be the initial sign of hypoglycemia, bacteremia, meningitis, shock, or pulmonary hypertension. Peripheral acrocyanosis is common and does not usually warrant concern.
Pallor, in addition to anemia or acute hemorrhage, should suggest hypoxia, asphyxia, hypoglycemia, sepsis, shock, or adrenal failure.
Hypotension in term infants suggests shock from hypovolemia (hemorrhage, dehydration), the systemic inflammatory response syndrome (bacterial sepsis, intrauterine infection), cardiac dysfunction (left heart obstructive lesions—hypoplastic left heart syndrome, myocarditis, asphyxia-induced myocardial stunning, anomalous coronary artery), pneumothorax, pneumopericardium, pericardial effusion, or metabolic disorders (hypoglycemia, adrenal insufficiency–salt-losing adrenogenital syndrome). Hypotension is a common problem in sick preterm infants and may be due to any of the problems noted in a term infant. It may develop in preterm infants with severe respiratory distress syndrome. Strategies used to support blood pressure include volume expansion (normal saline is equally as effective as 5% albumin), pressors (dopamine, dobutamine, epinephrine), and corticosteroids. Some infants weighing <1,000>
Convulsions usually point to a disorder of the CNS and suggest hypoxic-ischemic encephalopathy, intracranial hemorrhage, cerebral anomaly, subdural effusion, meningitis, hypocalcemia, hypoglycemia, cerebral infarction, benign familial seizures, and, rarely, pyridoxine dependence, hyponatremia, hypernatremia, inborn errors of metabolism, or drug withdrawal. Seizures beginning in the delivery room or shortly thereafter may be due to the unintentional injection of maternal local anesthetic into the fetus. Convulsions may also result from hyponatremia and water intoxication in the infant after the administration of large amounts of hypotonic fluid to the mother shortly before and during delivery.
Convulsions should be distinguished from the jitteriness that may be present in normal newborns, in infants of diabetic mothers, in those who experienced birth asphyxia or drug withdrawal, and in polycythemic neonates. Jitteriness resembling simple tremors may be stopped by holding the infant's extremity; it often depends on sensory stimuli and occurs when the infant is active, and it is not associated with abnormal eye movements. Tremors are often more rapid with a smaller amplitude than are tonic clonic seizures. Seizures in premature infants are often subtle and associated with abnormal eye (fluttering, deviation, stare) or facial (chewing, tongue thrusting) movements; the motor component is often that of tonic extension of the limbs, neck, and trunk. Term infants may have focal or multifocal, clonic or myoclonic movements, but they may also have more subtle seizure activity. Apnea may be the 1st manifestation of seizure activity, particularly in a premature infant. Seizures may adversely affect the subsequent neurodevelopmental outcome and even predispose to non-neonatal seizures. Seizures should be treated aggressively.
After severe birth asphyxia, infants may have motor automatisms characterized by oral-buccal-lingual movements, rotary limb activities (rowing, pedaling, swimming), tonic posturing, or myoclonus. These motor activities are not usually accompanied by time-synchronized electroencephalographic discharges, may not signify cortical epileptic activity, respond poorly to anticonvulsant therapy, and are associated with a poor prognosis. Such automatisms may represent cortical depression that produces a brainstem release phenomenon or subcortical seizures.
Lethargy may be a manifestation of infection, asphyxia, hypoglycemia, hypercapnia, sedation from maternal analgesia or anesthesia, a cerebral defect, and, indeed, almost any severe disease, including inborn errors of metabolism. Lethargy appearing after the 2nd day should, in particular, suggest infection. Lethargy with emesis suggests increased intracranial pressure or an inborn error of metabolism.
Irritability may be a sign of discomfort accompanying intra-abdominal conditions, meningeal irritation, drug withdrawal, infections, congenital glaucoma, or any condition producing pain. As in later infancy, the eardrums should always be examined as a possible source of pain. Hyperactivity, especially in a premature infant, may be a sign of hypoxia, pneumothorax, emphysema, hypoglycemia, hypocalcemia, CNS damage, drug withdrawal, neonatal thyrotoxicosis, bronchospasm, esophageal reflux, or discomfort from a cold environment.
Failure to feed well is seen in most sick newborn infants and should always occasion a careful search for infection, a central or peripheral nervous system disorder, intestinal obstruction, and other abnormal conditions.
Fever may be the result of too high an environmental temperature because of weather, overheated nurseries or isolettes/radiant warmers, or too many clothes. It is also noted in “dehydration fever” of newborn infants. If these causes of fever can be eliminated, serious infection (pneumonia, bacteremia, meningitis, and viral infections, particularly herpes simplex or enteroviruses) must be considered, although such infections often occur without provoking a febrile response in newborn infants. An unexplained fall in body temperature may accompany infection or other serious disturbances of the circulation or CNS. A sudden servo-controlled increase in isolette ambient temperature to maintain body temperature is a sign of temperature instability and may be associated with sepsis.
Periods of apnea, particularly in premature infants, may be associated with various disturbances. When apnea recurs or when the intervals are longer than 20 sec or are associated with cyanosis or bradycardia, an immediate diagnostic evaluation is needed.
Jaundice during the 1st 24 hr of life warrants diagnostic evaluation and should be considered to be due to hemolysis until proved otherwise. Septicemia and intrauterine infections such as syphilis, cytomegalovirus, and toxoplasmosis should also be considered, especially in infants with an increase in plasma direct-reacting bilirubin.
Jaundice after the 1st 24 hr may be “physiologic” or may be due to septicemia, hemolytic anemia, galactosemia, hepatitis, congenital atresia of the bile ducts, inspissated bile syndrome after erythroblastosis fetalis, syphilis, herpes simplex, or other congenital infections.
Vomiting during the 1st day of life suggests obstruction in the upper digestive tract or increased intracranial pressure. Roentgenographic studies are indicated when obstruction is suspected. Vomiting may also be a nonspecific symptom of an illness such as septicemia. It is a common manifestation of overfeeding or inexperienced feeding technique, pyloric stenosis, milk allergy, duodenal ulcer, stress ulcer, inborn errors of metabolism (hyperammonemia, metabolic acidosis), or adrenal insufficiency. Vomitus containing dark blood is usually a sign of a serious illness; the benign possibility of swallowed maternal blood should also be considered. Bile-stained vomitus strongly suggests obstruction below the ampulla of Vater and warrants contrast radiography.
Diarrhea may be a symptom of overfeeding (especially high–caloric density formula), acute gastroenteritis, or malabsorption, or it may be a nonspecific symptom of infection. Diarrhea may occur in conditions accompanied by compromised circulation of part of the intestinal or genital tract, such as mesenteric thrombosis, necrotizing enterocolitis, strangulated hernia, intussusception, and torsion of the ovary or testis.
Abdominal distention, usually a sign of intestinal obstruction or an intra-abdominal mass, may also be seen in infants with enteritis, necrotizing enterocolitis, isolated intestinal perforation, ileus accompanying sepsis, respiratory distress, ascites, or hypokalemia.
Failure to move an extremity (pseudoparalysis) suggests fracture, dislocation, or nerve injury. It is also seen in osteomyelitis and other infections that cause pain on movement of the affected part.
Pain in neonates may be unrecognized and/or undertreated. The intensive care of neonates may involve a number of painful procedures, including blood sampling, (heel stick, venous or arterial puncture), endotracheal intubation and suctioning, mechanical ventilation, and insertion of chest tubes and intravascular catheters. Pain in neonates results in obvious distress and acute physiologic stress responses, which may have developmental implications for pain in later life. Moreover, the knowledge that infants may experience pain contributes to the stress of parents of sick newborns.
Pain and discomfort are potentially avoidable problems during the treatment of sick infants. Preemptive relief from painful stimuli should be provided before pain or anxiety develops. The most frequently used drugs are intermittent or continuous doses of opioids (morphine, fentanyl) or benzodiazepines (midazolam, lorazepam). Although the long-term effects of opioids and sedatives are not well established, the 1st concern should be the treatment and/or prevention of acute pain. Continuous opiate infusions should be used with caution. Some minor but painful procedures on well neonates have also been managed with oral sucrose solutions, although the optimal dose is undetermined ( Table 2 ).
TABLE 1 -- Differential Diagnosis of Cyanosis in the Newborn
| Central or peripheral nervous system hypoventilation |
| Birth asphyxia |
| Intracranial hypertension, hemorrhage |
| Oversedation (direct or through maternal route) |
| Diaphragm palsy |
| Neuromuscular diseases |
| Seizures |
| Respiratory disease |
| Upper airway |
| Choanal atresia/stenosis |
| Pierre Robin syndrome |
| Intrinsic airway obstruction (laryngeal/bronchial/tracheal stenosis) |
| Extrinsic airway obstruction (bronchogenic cyst, duplication cyst, vascular compression) |
| Lower airway |
| Respiratory distress syndrome |
| Transient tachypnea |
| Meconium aspiration |
| Pneumonia (sepsis) |
| Pneumothorax |
| Congenital diaphragmatic hernia |
| Pulmonary hypoplasia |
| Cardiac right-to-left shunt |
| Abnormal connections (pulmonary blood flow normal or increased) |
| Transposition of great vessels |
| Total anomalous pulmonary venous return |
| Truncus arteriosus |
| Hypoplastic left heart syndrome |
| Single ventricle or tricuspid atresia with large ventricular septal defect but without pulmonic stenosis |
| Obstructed pulmonary blood flow (pulmonary blood flow decreased) |
| Pulmonic atresia with intact ventricular septum |
| Tetralogy of Fallot |
| Critical pulmonic stenosis with patent foramen ovale or atrial septal defect |
| Tricuspid atresia |
| Single ventricle with pulmonic stenosis |
| Ebstein malformation of the tricuspid valve |
| Persistent fetal circulation (persistent pulmonary hypertension of newborn) |
| Methemoglobinemia |
| Congenital (hemoglobin M, methemoglobin reductase deficiency) |
| Acquired (nitrates, nitrites) |
| Inadequate ambient O2 or less O2 delivered than expected (rare) |
| Disconnection of O2 supply to nasal cannula, head hood |
| Connection of air, rather than O2, to a mechanical ventilator |
| Spurious/artifactual |
| Oximeter artifact (poor contact between probe and skin, poor pulse searching) |
| Arterial blood gas artifact (contamination with venous blood) |
| Other |
| Hypoglycemia |
| Adrenogenital syndrome |
| Polycythemia |
| Blood loss |
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From Smith F: Cyanosis. In Kliegman: Practical Strategies in Pediatric Diagnosis and Therapy.
TABLE 2 -- Pain in the Neonate: General Considerations
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Adapted from Anonymous: Prevention and management of pain and stress in the neonate.Pediatrics 2000;105:454–461; and Anand KJS, International Evidence-Based Group for Neonatal Pain: Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med 2001;155:173–180.
CONGENITAL ANOMALIES
Congenital anomalies are a major cause of stillbirths and neonatal deaths, but they are perhaps even more important as causes of acute illness and long-term morbidity. Anomalies are discussed in general in other chapters and specifically in the chapters on the various systems of the body. Early recognition of anomalies is important for planning care; with some, such as tracheoesophageal fistula, diaphragmatic hernia, choanal atresia, and intestinal obstruction, immediate medical and surgical therapy is essential for survival ( Table 3 ). Parents are likely to feel anxious and guilty on learning of the existence of a congenital anomaly and require sensitive counseling.
TABLE 3 -- Common Life-Threatening Congenital Anomalies
| NAME | MANIFESTATIONS |
| Choanal atresia | Respiratory distress in delivery room, apnea, unable to pass nasogastric tube through nares. Suspect CHARGE syndrome |
| Pierre Robin syndrome | Micrognathia, cleft palate, airway obstruction |
| Diaphragmatic hernia | Scaphoid abdomen, bowel sounds present in chest, respiratory distress |
| Tracheoesophageal fistula | Polyhydramnios, aspiration pneumonia, excessive salivation, unable to place nasogastric tube in stomach. Suspect VATER syndrome |
| Intestinal obstruction: volvulus, duodenal atresia, ileal atresia | Polyhydramnios, bile-stained emesis, abdominal distention. Suspect trisomy 21, cystic fibrosis, cocaine |
| Gastroschisis, omphalocele | Polyhydramnios, intestinal obstruction |
| Renal agenesis, Potter syndrome | Oligohydramnios, anuria, pulmonary hypoplasia, pneumothorax |
| Neural tube defects: anencephalus, meningomyelocele | Polyhydramnios, elevated α-fetoprotein, decreased fetal activity |
| Ductal-dependent congenital heart disease | Cyanosis, hypotension, murmur |
CHARGE, coloboma of the eye, heart anomaly, choanal atresia, retardation, and genital and ear anomalies; VATER, vertebral defects, imperforate anus, tracheoesophageal fistula, and radial and renal dysplasia