ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Ill-appearing infant (younger than 90 days of age): Causes

Ill-appearing infant (younger than 90 days of age): Causes
Literature review current through: Jan 2024.
This topic last updated: Aug 19, 2022.

INTRODUCTION — In addition to sepsis, the causes of ill appearance in an infant <90 days of age are reviewed here. The evaluation and management of ill-appearing infants and febrile infants younger than three months of age are discussed separately:

(See "Approach to the ill-appearing infant (younger than 90 days of age)".)

(See "The febrile infant (29 to 90 days of age): Outpatient evaluation" and "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates".)

TERMINOLOGY — For the purposes of this topic, ill appearance in a young infant refers to abnormalities in one or more components of the pediatric assessment triangle (see "Initial assessment and stabilization of children with respiratory or circulatory compromise", section on 'Pediatric assessment triangle'):

Appearance (any one of the following):

Decreased muscle tone (limp or weak)

Difficult to arouse (lethargic)

Unfocused staring (does not fix or follow)

Inconsolable crying

Weak cry

Breathing:

Decreased respiratory effort or apnea

or

Respiratory distress indicated by:

-Nasal flaring

-Intercostal, subcostal, or suprasternal retractions

-Head bobbing (extension of the head on inhalation and forward movement on exhalation)

-Grunting (harsh, medium-pitched, end-expiratory sound that occurs as the result of exhalation against a partially closed glottis)

-Abdominal breathing (use of abdominal muscles to assist the downward pull of the diaphragm)

Circulatory status (any one of the following):

Prolonged capillary refill time (>2 seconds)

Pallor

Mottling

Cyanosis

Cool distal extremities

DIFFERENTIAL DIAGNOSIS — Although infection is the most likely cause of ill appearance among neonates and young infants, a number of other clinical conditions have similar manifestations (table 1). After initial stabilization, a careful history and physical examination can often identify key findings that provide the underlying cause (table 2 and table 3). In addition, presenting features can help focus the evaluation on the most likely etiologies. (See "Approach to the ill-appearing infant (younger than 90 days of age)", section on 'Evaluation' and "Approach to the ill-appearing infant (younger than 90 days of age)", section on 'Targeted Evaluation'.)

Infection — Fever is commonly present in ill-appearing young infants with an infectious cause. However, ill-appearing young infants with normal or low core temperatures (eg, rectal temperature <36.5°C [97.7°F]) may also have serious infections. For example, in a retrospective study of over 3500 young infants discharged with a primary diagnosis of hypothermia, 5.6 percent had bacteremia, 2.4 percent had a urinary tract infection (UTI), and 0.2 percent had herpes simplex virus (HSV) infection. In addition, many infants with pertussis are afebrile [1]. (See "Bacterial meningitis in the neonate: Clinical features and diagnosis", section on 'Temperature instability'.)

Bacterial

Bacterial sepsis – Infants can develop sepsis with or without concomitant infections such as UTIs, bacteremia, meningitis, pneumonia, skin abscess or cellulitis, mastitis, omphalitis, bacterial gastroenteritis, septic arthritis, or osteomyelitis. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Invasive bacterial infection' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Invasive bacterial infection'.)

Possible pathogens include the following:

In the immediate newborn period, Escherichia coli and Group B Streptococcus are the most common causes of serious bacterial infection. As a result of universal screening of pregnant women, the incidence of early-onset Group B streptococcus infection has declined; E. coli is now the predominant pathogen; Listeria monocytogenes is a rare cause. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Pathogens and type of infections' and "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Etiologic agents'.)

Beyond the first weeks of life, late-onset disease with Group B streptococcus (in contrast with early-onset disease, the incidence is not reduced with maternal Group B streptococcus screening and intrapartum antibiotic prophylaxis), E. coli, and L. monocytogenes may occur, as may infections with Streptococcus pneumoniae, Neisseria meningitidis, and, to a much lesser extent, Haemophilus influenzae type b. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'Invasive bacterial infection' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Invasive bacterial infection' and "Group B streptococcal infections in nonpregnant adults", section on 'Epidemiology'.)

Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen in infants with skin infections or with known exposures. (See "Methicillin-resistant Staphylococcus aureus infections in children: Epidemiology and clinical spectrum", section on 'CA-MRSA infection'.)

In young infants, the origins of osteomyelitis and septic arthritis are typically hematogenous. (See "Hematogenous osteomyelitis in children: Epidemiology, pathogenesis, and microbiology", section on 'Pathogenesis' and "Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in infants and children".)

Ascending UTIs with pyelonephritis are the most common serious bacterial infections in neonates and young infants. Up to 10 percent of these children will have coexisting bacteremia or urosepsis. E. coli causes more than 80 percent of these infections. Clinically, it is not possible to distinguish lower from upper UTI in this age group. A conservative and appropriate approach is to assume pyelonephritis exists among febrile young children with abnormal urinalyses. (See "Urinary tract infections in infants and children older than one month: Clinical features and diagnosis", section on 'Younger children'.)

Posterior urethral valves (PUV) are obstructing membranous folds within the lumen of the posterior urethra in the newborn male. Male infants with PUV may present with urosepsis associated with findings of failure to thrive, poor urinary stream, straining or grunting while voiding, elevated serum creatinine, and electrolyte abnormalities of chronic kidney disease (eg, metabolic acidosis and hyperkalemia). (See "Clinical presentation and diagnosis of posterior urethral valves", section on 'Clinical manifestations' and "Clinical presentation and diagnosis of posterior urethral valves", section on 'Diagnosis'.)

Bacterial meningitis among neonates and infants is caused by the same organisms that cause sepsis (see "Bacterial meningitis in the neonate: Clinical features and diagnosis" and "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Epidemiology'). The incidence of bacterial meningitis in this age group has been declining because of universal screening and intrapartum antibiotic prophylaxis for Group B streptococcal disease and the introduction of conjugate vaccines against H. influenza type b and Pneumococcus. Furthermore, outside of the first month of life, the incidence of bacterial meningitis among those with pyelonephritis is no higher when compared with those without pyelonephritis. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on '29 to 60 days old'.)

Pertussis – Pertussis is a ubiquitous and highly contagious infection with significant morbidity and mortality for young infants. Pertussis may present as respiratory failure, apnea and/or bradycardia, or a brief resolved unexplained event (BRUE). Symptoms may be nonspecific, including feeding difficulties, tachypnea, and cough. Gagging, vomiting, apnea, cyanosis, and/or bradycardia often develop during paroxysms of cough. (See "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Infants younger than 12 months'.)

Pertussis should be suspected (regardless of vaccination status or wheezing) in infants <4 months with a cough illness, usually without significant fever, who have (see "Pertussis infection in infants and children: Clinical features and diagnosis", section on 'Infants <4 months'):

Cough that is not improving (of any duration); the cough may or may not be paroxysmal (movie 1)

Rhinorrhea in which the nasal discharge remains watery

Apnea, seizures, cyanosis, vomiting, or poor weight gain

Leukocytosis with lymphocytosis (white blood cell [WBC] count ≥20,000 cells/microL with ≥50 percent lymphocytes)

Pneumonia

Household contact with a prolonged cough

There should be a low threshold to suspect pertussis in young infants, given the risk of serious complications. Clinical suspicion of pertussis in infants, especially those younger than four months, should trigger immediate treatment. Laboratory confirmation should not delay the initiation of treatment. Early diagnosis and prompt treatment, as well as other precautionary measures, are essential to prevention of transmission. (See "Pertussis infection in infants and children: Treatment and prevention", section on 'Antimicrobial therapy'.)

Infant botulism – Infants develop botulism from the ingestion of Clostridium botulinum spores (air-borne, soil-borne, or from food), rather than preformed botulinum toxin. The toxin, which impairs impulses at the neuromuscular junction by blocking acetylcholine release, is then produced by organisms that colonize the infant's gastrointestinal tract. The disease is more common among breast-fed infants. Symptoms initially include hypotonia, constipation, and poor feeding, and progress to respiratory failure. The diagnosis of infant botulism should be suspected in any infant with acute onset of weak suck, ptosis, decreased activity, or constipation. A presumptive diagnosis should be made based upon the clinical presentation and electromyography while confirmatory stool studies are pending. The diagnosis and treatment of infant botulism are discussed in greater detail separately. (See "Neuromuscular junction disorders in newborns and infants", section on 'Infant botulism'.)

Viral

Overwhelming viral infection – Life-threatening viral infections among neonates are most often caused by herpes simplex virus (HSV), enterovirus, or parechovirus. Cytomegalovirus (CMV) can cause life-threatening infection in preterm infants.

Herpes simplex virus (HSV) – HSV can cause life-threatening disseminated or central nervous system (CNS) infection in the newborn. The diagnosis should be suspected among infants who have any of the following findings (see "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Clinical manifestations'):

-Maternal HSV (may not elicit this history if first infection for mother, and the likelihood of transmission is significantly higher than with recurrent HSV in the mother)

-Ill appearance

-Vesicular rash

-Mucosal ulcers

-Seizures or history of seizures

-Cerebrospinal fluid pleocytosis or red blood cells

-Elevated liver enzymes

-Pneumonitis

As many as one-third of these neonates do not have skin vesicles at presentation, and many are afebrile, making the diagnosis more challenging. Infection is acquired during the birthing process, and initial symptoms typically appear in the first three weeks of life. The peak incidence of CNS disease is from 10 to 17 days of life. Those with disseminated infection may have earlier clinical manifestations. (See "Neonatal herpes simplex virus infection: Clinical features and diagnosis", section on 'Clinical suspicion'.)

The indications for the empiric use of acyclovir are discussed separately. (See "Neonatal herpes simplex virus infection: Management and prevention", section on 'Indications'.)

Enterovirus and parechovirus – Although typically associated with a self-limiting febrile illness that is sometimes accompanied by viral meningitis, certain enteroviral serotypes, such as group B coxsackievirus serotypes 2 to 5 and echovirus 11, may also produce myocarditis or hepatitis among neonates. Infected infants may present with a fulminant illness characterized by signs of decreased cardiac output, including hypotension, poor pulses, and decreased perfusion. Malignant arrhythmias are common. Evidence of viral myocarditis has been described in association with BRUEs and sudden infant death beyond the neonatal period as well. (See "Clinical manifestations and diagnosis of myocarditis in children".)

Because the infection is most often acquired from a symptomatic mother in the perinatal period, symptoms typically develop between three and seven days of life. However, approximately one-third of cases have a biphasic illness with a period of one to seven days of apparent well-being interspersed between the initial symptoms and the appearance of more serious manifestations. (See "Enterovirus and parechovirus infections: Clinical features, laboratory diagnosis, treatment, and prevention", section on 'Neonates'.)

Cytomegalovirus (CMV) – Infants who are preterm and/or very low birth weight (VLBW; birth weight <1500 grams) are especially vulnerable to severe CMV disease. Infection may become apparent as early as three weeks and as late as three to six months of age. A sepsis-like syndrome occurs in approximately 15 percent of infected VLBW infants and is associated with hepatosplenomegaly, hepatitis, pneumonitis, and abnormalities of blood counts (including lymphopenia, neutropenia, and/or thrombocytopenia). (See "Overview of cytomegalovirus infections in children", section on 'Early postnatal infection'.)

Bronchiolitis due to respiratory syncytial virus (RSV) and other viruses – Young infants, particularly those who are less than two months of age (ie, postmenstrual age <48 weeks) and premature, may develop apnea with bronchiolitis. Some may present with severe apnea and ill appearance before they develop typical signs of bronchiolitis, such as respiratory distress or wheezing. Although bronchiolitis is diagnosed clinically in older infants, chest radiographs and laboratory studies are frequently warranted in ill-appearing infants to confirm the clinical diagnosis and assess for the extent of lung involvement. (See "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Apnea' and "Bronchiolitis in infants and children: Clinical features and diagnosis", section on 'Diagnosis'.)

Influenza – The influenza virus is highly contagious, resulting in seasonal epidemics. Influenza-like illness is marked by fever and signs of lower respiratory tract disease, such as coughing. Infants may also present with vomiting, poor feeding, or malaise, and along with the older adults, they suffer the greatest morbidity and mortality from complications such as pneumonia and encephalitis. Those with significant comorbidities such as prematurity or pulmonary or cardiac diseases are at greatest risk for adverse outcomes. During influenza season, an evaluation for influenza virus infection should be pursued in all ill-appearing febrile infants and laboratory confirmation is warranted. (See "Seasonal influenza in children: Clinical features and diagnosis", section on 'Clinical features' and "Seasonal influenza in children: Clinical features and diagnosis", section on 'Whom to test'.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – Although SARS-CoV-2 can cause severe respiratory distress with fever and cough in infants younger than three months of age, many infants will have a respiratory illness that is clinically indistinguishable from that caused by other viruses. All hospitalized febrile infants and those discharged but with public health indications (eg, household contact who is an essential worker or at high risk of severe infection) should undergo SARS-CoV-2 testing. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'In infants <12 months of age'.)

Acute bilirubin encephalopathy (kernicterus) — Unconjugated bilirubin is a neurotoxin, which, at very high levels, can cause acute bilirubin encephalopathy (ABE) with permanent neurologic sequelae (kernicterus). Term infants may develop bilirubin neurotoxicity when total serum bilirubin concentrations exceed 25 mg/dL (513 micromol/L).

Risk factors for ABE include:

Gestation <37 weeks

Cephalohematoma or significant bruising from birth trauma

Hemolytic disease

Jaundice within the first 24 hours of life

Predischarge total serum, plasma, or transcutaneous bilirubin in the high-risk zone (figure 1)

Exclusive but suboptimal breastfeeding associated with weight loss of >10 percent of birth weight

Concurrent sepsis

ABE typically progresses through three phases (see "Unconjugated hyperbilirubinemia in neonates: Risk factors, clinical manifestations, and neurologic complications", section on 'Acute bilirubin encephalopathy (ABE)'):

Early – In the early phase, the clinical signs may be subtle. The infant is sleepy but arousable, and when aroused has mild to moderate hypotonia and a high-pitched cry.

Intermediate – If there is no intervention, the intermediate phase evolves with progression and persistence of hyperbilirubinemia. The infant can be febrile, lethargic with a poor suck, or irritable and jittery with a strong suck. The cry can be shrill, and the infant is difficult to console. Mild to moderate hypertonia develops, beginning with backward arching of the neck (retrocollis) and trunk (opisthotonos) with stimulation. An emergency exchange transfusion at this stage might prevent permanent bilirubin-induced neurologic dysfunction.

Advanced – The advanced phase is characterized by apnea, inability to feed, fever, seizures, and a semicomatose state that progresses to coma. Hypertonicity presents as persistent retrocollis and opisthotonos with bicycling or twitching of the hands and feet. The cry is inconsolable, or may be weak or absent. Death is due to respiratory failure or intractable seizures.

The diagnosis is based upon elevated indirect bilirubin for age (calculator 1) in association with these clinical findings. The management of ABE is discussed separately. (See "Unconjugated hyperbilirubinemia in term and late preterm newborns: Escalation of care".)

Cardiac conditions

Arrhythmias — Arrhythmias, of which supraventricular tachycardia (SVT) is the most common, may go unrecognized. Initial signs are nonspecific and the infant typically tolerates the rapid heart rate for many hours or days before clinical deterioration. Episodes of SVT are usually paroxysmal and characterized by abrupt onset and termination. The heart rate is typically 220 to 280 beats per minute (bpm) and on electrocardiogram (ECG), patients exhibiting SVT have no beat-to-beat variability and little variability in rate, and the QRS interval is typically narrow (<80 msec). If SVT is persistent, the infant eventually develops congestive heart failure. Management of tachycardia in infants is provided in the algorithm (algorithm 1). (See "Clinical features and diagnosis of supraventricular tachycardia (SVT) in children", section on 'Clinical features' and "Clinical features and diagnosis of supraventricular tachycardia (SVT) in children", section on 'Heart failure'.)

In infants, severe bradycardia can be due to both sinus and atrioventricular (AV) node dysfunction. This most commonly results from hypoxemia, hypotension, and metabolic acidosis, although intrinsic conduction defects may also be causes. In severe bradycardia, cardiac output is insufficient, leading to poor systemic perfusion, shock, and ultimately cardiorespiratory arrest. Children who have bradycardia with poor perfusion or shock require immediate medical management (algorithm 2). (See "Bradycardia in children", section on 'Acute management of patients with poor perfusion'.)

Congenital heart disease — Infants with previously undiagnosed congenital heart disease who are seriously ill may have one of the following critical congenital heart defects requiring surgery or catheter manipulation before one year of life (table 4) (see "Identifying newborns with critical congenital heart disease" and "Congenital and pediatric coronary artery abnormalities"):

Left-side obstructive lesions (eg, hypoplastic left heart syndrome, critical aortic stenosis, coarctation of the aorta, or interrupted aortic arch)

Right-sided obstruction lesions (eg, Tetralogy of Fallot with pulmonary atresia, pulmonary atresia with intact ventricular septum, critical pulmonary stenosis, tricuspid atresia, or severe neonatal Ebstein anomaly)

Transposition of the great arteries

Truncus arteriosus

Total anomalous pulmonary venous return

Total anomalous left coronary artery arising from the pulmonary artery

Infants with cyanotic or obstructive heart disease, who are dependent on blood flow through the ductus arteriosus for pulmonary or systemic circulation, develop severe symptoms as the ductus closes over the first few days to weeks after birth (table 4). Depending upon the specific cardiac lesion and the delay in seeking care, infants may present with some combination of poor feeding, poor weight gain, respiratory distress, cyanosis, shock, acidosis, and congestive heart failure. Obstructive lesions manifested as respiratory distress, shock, and cyanosis may mimic sepsis. (See "Identifying newborns with critical congenital heart disease", section on 'Clinical features'.)

The more common forms of cyanotic congenital heart disease may be clinically distinguished from each other and other causes of central cyanosis based upon characteristic physical examination, chest radiography, and electrocardiogram findings (table 5). Ultimately, echocardiography is necessary to make the diagnosis and to differentiate cyanotic congenital heart disease from cyanosis due to respiratory disease. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Echocardiography'.)

Coarctation of the aorta often presents with diminished femoral pulses compared with the right brachial pulse and right-upper extremity blood pressure greater than lower extremity blood pressure. Echocardiography confirms the diagnosis and determines the underlying cardiac anatomy and function. (See "Clinical manifestations and diagnosis of coarctation of the aorta".)

Ill appearing neonates with uncorrected ductal-dependent lesions generally require administration of prostaglandin E1., as discussed in detail separately. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Initial management'.)

Infants with unrepaired tetralogy of Fallot may develop episodes of severe cyanosis ("tet spell") in association with stresses such as fever, pain, crying, feeding, or having a bowel movement. The cyanosis can progress to unconsciousness and cardiac arrest if prolonged. Emergency management is discussed in detail separately. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis", section on 'Tet spells' and "Tetralogy of Fallot (TOF): Management and outcome", section on 'Tet spells'.)

Infants with surgically palliated complex congenital heart disease often have cardiovascular shunts. Shunt thrombosis must be strongly considered in such infants should they experience an abrupt change in their cardiovascular status. Emergency echocardiography and consultation with pediatric cardiovascular surgery specialists are essential to diagnosis and further treatment. (See "Hypoplastic left heart syndrome: Management and outcome", section on 'Post-stage I management'.)

Kawasaki disease — Kawasaki disease (KD) is rare among young infants. However, in this age group, the presentation is frequently incomplete or atypical. As a result, patients are at increased risk for coronary artery aneurysms, primarily because of delay in treatment. The diagnosis should be considered in any child under age six months with five or more consecutive days of unexplained fever. (See "Kawasaki disease: Epidemiology and etiology", section on 'Epidemiology' and "Kawasaki disease: Clinical features and diagnosis", section on 'Clinical manifestations'.)

Supporting the diagnosis of incomplete KD (ie, fever with less than four additional features (table 6)), are lab abnormalities including elevated WBC and platelet counts, transaminases, and acute phase reactants, as well as anemia and pyuria. Echocardiogram (ECHO) should be performed in these patients. In addition, all infants less than six months with seven or more days of unexplained fever (even without KD signs) warrant laboratory testing and ECHO based on the lab results. The demonstration of coronary artery aneurysms on ECHO may be seen in up to 10 percent of children who never meet criteria for KD. (See "Kawasaki disease: Clinical features and diagnosis", section on 'Infants' and "Kawasaki disease: Clinical features and diagnosis", section on 'Diagnosis'.)

Child abuse — Young infants with severe inflicted injury (typically, head injury) often present with a sudden onset of altered mental status, seizures, and/or respiratory distress. Fever may be present in infants with intracranial bleeding. History of trauma is typically absent or implausible. Because signs of external injury such as burns or contusions may be minimal or absent, one must maintain a high level of suspicion (table 7 and table 8). Key diagnostic actions after stabilization include (see "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Evaluation' and "Child abuse: Evaluation and diagnosis of abusive head trauma in infants and children", section on 'Diagnosis'):

Skeletal survey

Neuroimaging

Laboratory studies (eg, complete blood count, electrolytes, liver enzymes, lipase, and a urinalysis)

Eye examination by an ophthalmologist

Consultation with a multidisciplinary child abuse team, whenever possible

Congenital adrenal hyperplasia — Congenital adrenal hyperplasia (CAH) is a group of inherited disorders of impaired cortisol synthesis. More than 95 percent of cases are due to 21-hydroxylase deficiency, which classically manifests in infancy as virilization and adrenal insufficiency (see "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children"). Universal newborn screening for CAH due to 21-hydroxylase deficiency is performed in many high-income countries and may permit detection before adrenal insufficiency occurs. However, newborn screening does not detect all forms of CAH (see "Uncommon congenital adrenal hyperplasias"). Male infants are usually more difficult to recognize and may present with adrenal crisis. Adrenal crisis typically develops within the first few days to weeks of life. Clinical manifestations include (table 9) (see "Genetics and clinical manifestations of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency" and "Clinical manifestations and diagnosis of adrenal insufficiency in children", section on 'Adrenal crisis'):

Vomiting

Diarrhea

Dehydration

Hyponatremia

Hyperkalemia

Hypoglycemia

Hypotension

Masculinization of external genitalia (female infants only)

A rapid overview provides the initial steps in the diagnosis and treatment of adrenal crisis (table 10), which are discussed in detail separately. (See "Clinical manifestations and diagnosis of adrenal insufficiency in children" and "Treatment of adrenal insufficiency in children".)

Glucose and electrolyte abnormalities

Hypoglycemia — Hypoglycemia is defined as a plasma glucose concentration low enough to cause signs and symptoms of brain dysfunction (neuroglycopenia). Because the response to hypoglycemia occurs across a range of plasma glucose concentrations and signs of hypoglycemia are not reliably identifiable, especially in young infants, hypoglycemia cannot be defined as a single plasma glucose concentration. However, the threshold for obtaining diagnostic data (often referred to as the "critical sample") and for confirming a diagnosis of hypoglycemia in infants outside of the neonatal transition period is 50 mg/dL (2.8 mmol/L). The immediate management of an ill-appearing infant with hypoglycemia is provided in the table (table 11) and discussed separately. (See "Approach to hypoglycemia in infants and children", section on 'Immediate management'.)

Hypoglycemia can be caused by various metabolic, endocrinologic, toxic, and infectious etiologies; its discovery warrants further diagnostic evaluation, which is discussed separately. (See "Causes of hypoglycemia in infants and children" and "Approach to hypoglycemia in infants and children".)

Hyponatremia — Infants with acute hyponatremia (developed over a period of less than 48 hours) are more likely to be symptomatic and are at risk for complications as there has not been sufficient time for cerebral adaption to occur. Symptoms also are dependent on the severity of hyponatremia. In infants, severe hyponatremia (serum sodium <125 mEq/L) usually occurs as the result of water intoxication (intake of excessive amounts of free water; commonly due to improper mixing of infant formula), excessive renal losses (such as with CAH), or excessive gastrointestinal losses. Occasionally, infants with cystic fibrosis may present with hyponatremic dehydration. (See "Hyponatremia in children: Etiology and clinical manifestations", section on 'Acute hyponatremia'.)

Young infants with hyponatremia may develop lethargy, coma, or seizures, and the seizures may be refractory to anticonvulsants until the underlying metabolic derangement is corrected. The emergency treatment of acute symptomatic hyponatremia is provided separately. (See "Hyponatremia in children: Evaluation and management", section on 'Acute symptomatic hyponatremia'.)

Hypernatremia — Causes of hypernatremia (serum sodium 150 mEq/L or more) include sodium poisoning, excessive loss of free water (as can occur with arginine vasopressin deficiency or resistance [previously called central or nephrogenic diabetes insipidus, respectively]), or loss of water in excess of sodium losses. Severe hypernatremic dehydration has been reported in association with breastfeeding difficulties. Lethargy, irritability, seizures, and/or coma may occur with hypernatremia. Initial treatment consists of fluid resuscitation of hypovolemic shock followed by careful replacement of the free water deficit (see "Hypernatremia in children", section on 'Volume status and emergent fluid resuscitation'). Infants with hypernatremia warrant additional evaluation to determine the cause. (See "Hypernatremia in children".)

Hypocalcemia — In infants, severe hypocalcemia presents with:

Increased neuromuscular irritability (eg, jitteriness or muscle jerking induced by noise or other stimuli)

Tetany

Generalized or focal clonic seizures

Rare presentations include inspiratory stridor caused by laryngospasm [2], wheezing caused by bronchospasm, or vomiting possibly resulting from pylorospasm.

A low ionized calcium (<1 mmol/L) confirms the diagnosis of hypocalcemia. A variety of genetic and acquired conditions can cause hypocalcemia (table 12). In addition to ionized calcium, the following are important laboratory studies to obtain prior to treatment, whenever possible, to help narrow the differential diagnosis (see "Etiology of hypocalcemia in infants and children" and "Neonatal hypocalcemia", section on 'Symptomatic infants'):

Blood urea nitrogen and serum creatinine

Serum phosphate, magnesium, and alkaline phosphatase

Parathyroid hormone

25-hydroxyvitamin D

Infants with tetany, seizures, tachyarrhythmias, or laryngospasm attributable to hypocalcemia without hypomagnesemia warrant treatment with intravenous calcium [3]. Suggested pediatric dosing and safe administration are discussed separately (see "Primary drugs in pediatric resuscitation", section on 'Calcium'). Infants with serious signs of hypocalcemia accompanied by hypomagnesemia require treatment with intravenous magnesium [3]. (See "Primary drugs in pediatric resuscitation", section on 'Magnesium sulfate'.)

The evaluation and management of neonatal hypocalcemia is described separately. (See "Neonatal hypocalcemia".)

Hypothermia — Hypothermia (core body temperature below 35°C [95°F]) frequently occurs in young infants because they are prone to heat loss due to their high body surface to mass ratio and because they lack compensatory mechanisms, such as shivering, to respond to cold stress. Instead, they rely on intense peripheral vasoconstriction to maintain core temperature. A precise measurement of core body temperature is needed to confirm the diagnosis and guide treatment.

Hypothermia may be due to environmental exposure or secondary to serious medical illness (table 13). Hypothermia due to medical illness is typically mild (core body temperature 32 to 35°C [90 to 95°F]). However, in ill-appearing young infants, a core temperature <36.5°C (97.7°F) may also be a sign of a severe infection. (See 'Infection' above.)

Common features of moderate to severe environmental hypothermia in infants include decreased responsiveness, apnea, bradycardia, and prolonged capillary refill time. (See "Hypothermia in children: Clinical manifestations and diagnosis" and "Hypothermia in children: Management".)

Inborn errors of metabolism — Inborn errors of metabolism (IEM) should be suspected in all ill-appearing young infants. Although individual defects are uncommon in the general population, IEM account for a significant portion of disease among infants. Testing for IEM may be included in newborn screening tests. However, infants can present before the results are reported.

Amino acid disorders, organic acidemias, urea cycle disorders, disorders of carbohydrate metabolism, fatty acid oxidation defects, and mitochondrial disorders may present with an acute metabolic crisis that can be triggered by intake of protein or certain carbohydrates or infection. Specific critical presentations may manifest as (see "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management"):

Hypoglycemia

Unexplained metabolic acidosis with an increased anion gap

Respiratory alkalosis

Hyperammonemia

Inappropriate ketonuria

Thus, measurement of blood glucose, urine ketones, serum lactate, acid-base status (venous or arterial blood gas), and ammonia can provide an early indication of the presence and type of IEM (table 14). As an example, newborns with urea cycle disorders or organic acidemias generally present with an acute, severe illness characterized by lethargy, poor feeding, vomiting, and shock, with hyperammonemia and profound acidosis. Switching from breast milk to regular formula with the accompanying increase in dietary protein is often an inciting event. (See "Urea cycle disorders: Clinical features and diagnosis".)

Galactosemia is notable for its association with urosepsis, usually caused by E. coli and causes metabolic acidosis, reducing substances in the urine, glycosuria, and conjugated or unconjugated hyperbilirubinemia. (See "Galactosemia: Clinical features and diagnosis", section on 'Classic galactosemia'.)

General laboratory evaluation can help to distinguish among the types of metabolic conditions and help guide specialized testing (table 15). These studies also help to exclude metabolic disease. (See "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management", section on 'Laboratory findings'.)

Immediate management for infants with IEM is discussed separately. (See "Metabolic emergencies in suspected inborn errors of metabolism: Presentation, evaluation, and management", section on 'Immediate management'.)

Surgical conditions

Congenital aganglionic megacolon (Hirschsprung disease) — The majority of patients with Hirschsprung disease (HD) are diagnosed in the neonatal period. The diagnosis can be suggested by a delay in passage of the first meconium (greater than 48 hours of age). By 48 hours of life, 100 percent of normal full-term neonates will pass meconium. By contrast, 50 to 90 percent of infants with HD will fail to pass meconium within the first 48 hours of life. Thus, passage of stool within the first one to two days of life does not exclude the diagnosis. Patients present with symptoms of distal intestinal obstruction:

Bilious emesis

Abdominal distension

Failure to pass meconium or stool

There may be an explosive expulsion of gas and stool after the digital rectal examination (squirt sign or blast sign), which may relieve the obstruction temporarily. The diagnosis is usually supported by contrast enema or anorectal manometry and is established by rectal biopsy. (See "Congenital aganglionic megacolon (Hirschsprung disease)", section on 'Clinical features'.)

Affected infants may also present initially with enterocolitis, a potentially life-threatening illness in which patients have a sepsis-like picture that includes:

Fever

Vomiting

Diarrhea

Abdominal distension, which can progress to toxic megacolon

Patients with enterocolitis require fluid resuscitation, intravenous antibiotic therapy to cover bowel flora, rectal irrigations, and, in rare cases, an emergency colostomy. A rare complication of HD is volvulus, which can affect the sigmoid and less commonly the transverse colon and cecum. (See "Emergency complications of Hirschsprung disease".)

Gonadal torsion — Although rare, testicular and ovarian torsion can present in the neonatal period and present with testicular swelling or, in female infants, painful inguinal swelling (incarcerated ovary) or abdominal or pelvic pain. A high index of suspicion and corroboration by Doppler ultrasonography and/or surgical consultation is necessary to make the diagnosis. (See "Neonatal testicular torsion", section on 'Postnatal' and "Ovarian and fallopian tube torsion", section on 'Fetuses'.)

Incarcerated hernia — An inguinal hernia develops when intraabdominal contents enter the inguinal canal through a patent processus vaginalis. An incarceration results when the hernia cannot be reduced back into the intraabdominal cavity. Incarceration can rapidly progress to strangulation, in which hernia contents become ischemic.

Infants with an incarcerated inguinal hernia usually are irritable and crying. Vomiting and abdominal distention may develop, depending on the duration of incarceration and whether or not intestinal obstruction has occurred. Physical examination of children with incarcerated inguinal hernias usually is diagnostic. A firm, discrete inguinal mass, which may extend to the scrotum or labia majora, can be palpated in the groin. The mass usually is tender and often is surrounded by edema with erythema of the overlying skin. The testicle may appear dark blue because of venous congestion caused by pressure on the spermatic cord.

Intussusception — Intussusception is rare in infants <90 days of age but may occur due to lymphoid hyperplasia or the presence of a congenital anomaly (eg, Meckel diverticulum or intestinal duplication) that serves as a lead point. In this age group, clinical manifestations may include:

Vomiting

Irritability with drawing up of the legs

Abdominal distension

Stool with gross or occult blood

Of note, intussusception can present with lethargy and ill appearance in young infants without any of the above findings. The diagnosis of intussusception is made radiographically, most commonly with ultrasonography (image 1). (See "Intussusception in children".)

Malrotation with volvulus — Malrotation develops as a result of an arrest of normal rotation of the embryonic gut. Abnormal mobility of the small bowel, as the result of a narrow mesenteric base, allows the mesentery to twist. Volvulus occurs when small bowel twists around the superior mesenteric artery, causing vascular compromise to large portions of the midgut (figure 2). This leads to ischemia and necrosis of the bowel that can quickly become irreversible. Vomiting, which is almost always bilious (green), occurs in >90 percent of newborns with volvulus and is by far the most common presenting symptom of malrotation in infancy. Abdominal distension and tenderness are typically also present on physical examination. (See "Intestinal malrotation in children".)

The approach to diagnosis of malrotation is provided in the algorithm (algorithm 3) and discussed in detail separately. (See "Intestinal malrotation in children", section on 'Diagnosis'.)

Meconium ileus (cystic fibrosis) — Meconium ileus is a disorder of the neonate caused by the obstruction of the small intestines at the level of the terminal ileum with inspissated meconium and is the most common presenting finding in young infants with cystic fibrosis. The widespread use of prenatal carrier testing and prenatal detection of meconium ileus by ultrasound enables clinicians to counsel patients and plan proactive management of this complication of cystic fibrosis.

Infants with meconium ileus generally present during the first three days of life with abdominal distension and failure to pass meconium, with or without vomiting. Affected infants are initially stabilized with nasogastric decompression and correction of fluid and electrolyte abnormalities. An abdominal plain film should be performed to look for evidence of dilated bowel loops, perforation, calcifications, or other abnormalities (image 2). If there is no evidence of perforation, hyperosmotic contrast enema radiography is performed to confirm the diagnosis, using a water-soluble agent. In patients with meconium ileus, the contrast radiograph typically reveals a small-caliber colon (microcolon of disuse) and meconium pellets in the terminal ileum. The ileum proximal to the obstruction is dilated (image 3). The hyperosmolar contrast often breaks up the meconium mass and clears the obstruction. However, approximately one-half of infants with meconium ileus have complications that require surgical intervention. (See "Cystic fibrosis: Overview of gastrointestinal disease", section on 'Meconium ileus'.)

Neonatal appendicitis — Neonatal appendicitis has been reported infrequently. The appendix is typically perforated at the time of diagnosis among infants. Symptoms are nonspecific and include lethargy, irritability, poor feeding, and vomiting. Infants often have abdominal distension with tenderness and signs of sepsis, such as fever, tachycardia, tachypnea, and poor skin perfusion. (See "Acute appendicitis in children: Clinical manifestations and diagnosis", section on 'Neonates (0 to 30 days)'.)

Necrotizing enterocolitis — Necrotizing enterocolitis (NEC) is characterized by bowel wall necrosis that may lead to perforation (image 4). It is most common in premature neonates, especially those of VLBW. It may rarely occur in full-term infants, usually within the first 10 days of life. Term infants who develop NEC typically have an underlying condition, such as congenital heart disease or protracted diarrhea. Abdominal findings consist of bilious emesis, abdominal pain and distension, and rectal bleeding. Systemic signs are nonspecific and include apnea, respiratory failure, lethargy, poor feeding, temperature instability, or hypotension resulting from septic shock in the most severe cases. (See "Neonatal necrotizing enterocolitis: Clinical features and diagnosis".)

Pyloric stenosis — Hypertrophy of both the circular and longitudinal muscular layers of the pylorus results in obstruction. This is a common condition estimated to occur in approximately 1 of 300 live births. (See "Infantile hypertrophic pyloric stenosis", section on 'Pathogenesis'.)

Patients typically come to medical attention at three to six weeks of age with a complaint of progressively worsening projectile, nonbilious emesis. Patients with significant hypokalemic, hypochloremic metabolic alkalosis and dehydration may appear listless and cachectic. However, a heightened clinical awareness and the liberal use of ultrasound to establish the diagnosis has led to early diagnosis and better outcomes. Thus, the classic presentation with a prolonged duration of vomiting and emaciation accompanied by a palpable mass in the right-upper quadrant and a hypokalemic metabolic alkalosis on blood chemistries is less common. (See "Infantile hypertrophic pyloric stenosis", section on 'Clinical manifestations'.)

Toxic exposures — Young infants may rarely become ill due to toxic exposures.

Carbon monoxide poisoning — Infants may develop carbon monoxide poisoning as the result of occult exposure from sources such as improperly vented home heating systems or automobile exhaust fumes [4,5]. The diagnosis may be difficult to make without a history of exposure or symptomatic contacts. Presenting symptoms include lethargy and irritability. Because of their high oxygen consumption, young infants may be the first to display symptoms. An elevated carboxyhemoglobin blood level confirms the diagnosis. (See "Carbon monoxide poisoning".)

Ingestion of substances in breast milk — Toxicity has been described for breastfeeding infants whose mothers have used drugs of abuse (eg, heroin, cocaine, phencyclidine, and marijuana) and, rarely, maternal medications [6,7]. Maternal history of drug use and determination of all substances being used by a breastfeeding mother is essential to establishing this toxic exposure. Maintaining a general broad differential and high suspicion along with focused physical examination for toxidrome features is important to the diagnosis. A urine drug screen from the infant can provide supporting evidence for toxicity due to drugs of abuse. (See "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Management and outcomes".)

Malicious drug exposure — Although rare, malicious drug exposure should be considered in all ill-appearing young infants with altered mental status (lethargy, coma, or seizures), or a complicated medical presentation (eg, unexplained metabolic acidosis) in whom initial evaluation does not provide an explanation. Of over 1400 cases of malicious poisoning reported to the US National Poison Data System, three deaths occurred in infants younger than 90 days of age and were caused by diphenhydramine, methadone, or benzodiazepines [8]. Pharmaceutical medications may also be administered by caregivers to induce illness as a form of medical child abuse. (See "Medical child abuse (Munchausen syndrome by proxy)", section on 'Perpetrator actions'.)

Initial investigations should include a blood ethanol level and a rapid urine drug screen, preferably close in time to initial presentation. When obtaining such tests, the clinician should primarily test for poisons that are consistent with the patient's symptoms (eg, testing for ethanol, opioids, benzodiazepines, barbiturates, marijuana, and antihistamines in young infants who are lethargic and for cocaine or amphetamines in infants with seizures). If a screening test (eg, enzyme-mediated immunoassay for drugs of abuse) is positive, then a more definitive test should be performed to confirm and quantify the amount of substance present (eg, gas chromatography/mass spectrophotometry).

However, negative results do not exclude drug overdose. Studies beyond the typical rapid drugs of abuse screens may also be warranted. In these patients, consultation with a regional poison control center or medical toxicologist is advised to assist with recommendations for specific testing and identification of specialized laboratories where such testing can be performed. (See "Physical child abuse: Diagnostic evaluation and management", section on 'Toxicology'.)

Medication error — The clinician should obtain a careful history of all medications (including over-the-counter, naturopathic, and herbal supplements) and doses given to the infants. Because oral medications for infants are in liquid form, it is important to check the volume given and the drug concentration. Dosing errors with severe toxicity have been described with multiple medications including [9,10]:

Acetaminophen (see "Clinical manifestations and diagnosis of acetaminophen (paracetamol) poisoning in children and adolescents")

Hyoscyamine (anticholinergic toxicity) (see "Anticholinergic poisoning")

Methadone (for treatment of neonatal abstinence) (see "Opioid intoxication in children and adolescents")

Metoclopramide

Topical medications that contain local anesthetics (eg, eutectic mixture of lidocaine [EMLA], tetracaine, or benzocaine) are readily absorbed through the skin of young infants and can cause seizures, methemoglobinemia, or cardiac arrhythmias when applied in excess. (See "Clinical use of topical anesthetics in children" and "Subcutaneous infiltration of local anesthetics", section on 'Systemic toxicity'.)

Methemoglobinemia — Methemoglobinemia has been described in young infants in association with severe diarrheal illness and following exposure to oxidants (such as water or foods high in nitrites and some topical anesthetics) [11,12]. Infants are susceptible to acute methemoglobinemia because of the relative immaturity of the hemoglobin reductase enzyme system that maintains hemoglobin iron in a reduced state.

Patients with methemoglobinemia typically are cyanotic or ashen and, like those with cyanotic congenital heart disease, do not improve with supplemental oxygen. In contrast with infants with cyanotic congenital heart disease, however, oxygen saturation as measured with pulse oximetry, is normal or near-normal despite clinical duskiness. In addition, blood samples are dark red, chocolate, or brownish to blue in color and do not change with the addition of oxygen (picture 1). (See "Methemoglobinemia".)

Neonatal abstinence syndrome — An infant born to a mother with a substance use disorder is at risk for withdrawal, commonly referred to as neonatal abstinence syndrome (NAS). NAS is most commonly associated with opioid exposure. Affected infants typically have hyperarousal, irritability, increased tone with myoclonus, and may develop fever due to autonomic dysfunction. Timing of onset for NAS varies but can be prolonged more than five days after birth, especially when it is caused by longer-acting opioids such as methadone or buprenorphine. The clinical diagnosis of prenatal opioid exposure is based upon a history (or suspected history) of maternal opioid use disorder, positive maternal or infant urine toxicology screening for opioids, and/or neonatal findings that are consistent with NAS. Management of NAS is discussed separately. (See "Prenatal substance exposure and neonatal abstinence syndrome (NAS): Management and outcomes".)

SUMMARY AND RECOMMENDATIONS

Terminology – Ill appearance in a young infant refers to abnormalities in one or more components of the pediatric assessment triangle (appearance, circulation, and breathing). (See "Initial assessment and stabilization of children with respiratory or circulatory compromise", section on 'Pediatric assessment triangle'.)

Differential diagnosis – Although infection is the most likely cause of ill appearance in young infants <90 days of age, a number of other clinical conditions have similar manifestations (table 1). (See 'Differential diagnosis' above.)

Historical features, physical findings, and initial ancillary studies may provide clues to a specific diagnosis (table 2 and table 3). (See "Approach to the ill-appearing infant (younger than 90 days of age)", section on 'Evaluation'.)

Targeted evaluation – After initial stabilization and provision of empiric therapy as needed, a targeted evaluation based upon a detailed history and physical examination frequently identifies the underlying condition and guides definitive therapy. (See "Approach to the ill-appearing infant (younger than 90 days of age)", section on 'Targeted Evaluation' and "Approach to the ill-appearing infant (younger than 90 days of age)", section on 'Abnormal studies'.)

  1. Ramgopal S, Noorbakhsh KA, Pruitt CM, et al. Outcomes of Young Infants with Hypothermia Evaluated in the Emergency Department. J Pediatr 2020; 221:132.
  2. Gardner A, Ruch A. Not All Stridor Is Croup. Pediatr Emerg Care 2020; 36:e14.
  3. Nadar R, Shaw N. Investigation and management of hypocalcaemia. Arch Dis Child 2020; 105:399.
  4. Piatt JP, Kaplan AM, Bond GR, Berg RA. Occult carbon monoxide poisoning in an infant. Pediatr Emerg Care 1990; 6:21.
  5. O'Sullivan BP. Carbon monoxide poisoning in an infant exposed to a kerosene heater. J Pediatr 1983; 103:249.
  6. American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108:776.
  7. Bertino E, Varalda A, Di Nicola P, et al. Drugs and breastfeeding: instructions for use. J Matern Fetal Neonatal Med 2012; 25 Suppl 4:78.
  8. Yin S. Malicious use of pharmaceuticals in children. J Pediatr 2010; 157:832.
  9. Tzimenatos L, Bond GR, Pediatric Therapeutic Error Study Group. Severe injury or death in young children from therapeutic errors: a summary of 238 cases from the American Association of Poison Control Centers. Clin Toxicol (Phila) 2009; 47:348.
  10. Kang AM, Brooks DE. US Poison Control Center Calls for Infants 6 Months of Age and Younger. Pediatrics 2016; 137:e20151865.
  11. Pollack ES, Pollack CV Jr. Incidence of subclinical methemoglobinemia in infants with diarrhea. Ann Emerg Med 1994; 24:652.
  12. Murone AJ, Stucki P, Roback MG, Gehri M. Severe methemoglobinemia due to food intoxication in infants. Pediatr Emerg Care 2005; 21:536.
Topic 129373 Version 8.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟