eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Congenital Pneumonia

Author: Roger G Faix, MD, Professor, Department of Pediatrics (Neonatology), University of Utah School of Medicine
Contributor Information and Disclosures

Updated: Oct 19, 2007

Introduction

Background

Pneumonia is an inflammatory pulmonary process that may originate in the lung or be a focal complication of a systemic process. Abnormalities of airway patency as well as alveolar ventilation and perfusion frequently ensue due to various mechanisms. These derangements may significantly alter gas exchange and dependent cellular metabolism in the many tissues and organs that determine survival and contribute to quality of life. Such pathologic problems, superimposed on the underlying difficulties associated with the transition from intrauterine to extrauterine life, pose critical challenges to the immature human organism. Recognition, prevention, and treatment of these problems are major factors in the care of high-risk newborn infants.

This article focuses on pneumonia that presents within the first 24 hours after birth. Although pneumonia is an important cause of morbidity and mortality among newborn infants, it remains a difficult disease to prospectively identify and treat. Clinical manifestations are often nonspecific, sharing respiratory and hemodynamic signs with a host of noninflammatory processes. Radiographic and laboratory findings also have limited predictive value. Attempts to identify specific microbes responsible for pneumonia are often unsuccessful for multiple reasons; for example, the organisms may be difficult to recover from intrapulmonary sites without contamination by airway commensals, the organisms may be uncultivable primarily or because of ongoing antimicrobial treatment, or inflammation may result from noninfectious causes, such as aspiration of meconium, amniotic contents, food, blood, and other agents.

Pathophysiology

The lungs assume sole responsibility for neonatal gas exchange following separation of the fetus from the placenta; such exchange includes both uptake of oxygen and release of carbon dioxide and other excretory gases. The exchange occurs by conduction of humidified atmospheric gas and mixed venous blood to the alveolar interface where rapid diffusion across the single cell layers of the alveolar epithelium and capillary endothelium attains near equilibrium under ideal circumstances.

Host defenses in the lung

To prevent and minimize injury and invasion by microorganisms and foreign substances, various defense mechanisms have evolved, both systemically and within the respiratory tract. Some mechanisms are nonspecific and are directed against any invasive agent, whereas others are targeted against only microbes or substances with specific antigenic determinants. Many of the defenses are compromised in the fetus and newborn infant, resulting in more frequent breaches and consequent disruption of normal lung structure and function.

Nonspecific defenses include the glottis and vocal cords, ciliary escalator, airway secretions, migratory and fixed phagocytes, nonspecific antimicrobial proteins and opsonins, and the normal relatively nonpathogenic airway flora. Anatomic structures of the upper airway and associated reflexes discourage particulate material from entering, while coordinated movement of the microscopic cilia on the tracheal and bronchial epithelia tends to sweep particles and mucous up the airway and away from the alveoli and distal respiratory structures.

Mucoid airway secretions provide a physical barrier that minimizes epithelial adhesion and subsequent invasion by microorganisms. These secretions typically contain complement components, fibronectin, and other proteins that bind to microbes and render them more susceptible to ingestion by phagocytes. Alveolar and distal airway secretions also include whole surfactant, which facilitates opsonization and phagocytosis of pathogens, as well as surfactant-associated proteins A and D (Sp-A and Sp-D), both of which modulate phagocytosis, phagocyte production of oxyradicals, and cytokine elaboration. 

The secretions also contain directly inhibitory and microbicidal agents, such as iron-binding proteins, lysozymes, and defensins. Typical benign airway commensals, such as alpha-hemolytic streptococci and coagulase-negative staphylococci, occupy mucosal sites and elaborate bacteriocins and other substances that prevent more pathogenic organisms from adhesion, replication, and possible opportunistic invasion.

Immunologic defense mechanisms targeted against particular pathogens typically emanate from specifically primed lymphocytes following presentation of processed antigen by macrophages. These mechanisms include cytotoxic, killer, suppressor, and memory functions; systemic and secretory antibodies; and consequent cascades of cytokines, complement, vasomotor regulatory molecules, hemostatic factors, and other agents. Secretory antibodies are typically multimeric and contain secretory component and J chains that render them more opsonic and more resistant to microbial proteases. Many of the biochemical cascades triggered by specific immune responses serve to localize microbial invasion, amplify and focus recruitment of phagocytes to the affected sites, and directly disrupt the structural and metabolic integrity of the microbes.

Newborn infants typically have sterile respiratory mucosa at birth, with subsequent uncontested colonization by microorganisms from the mother or environment. Accelerated access to distal respiratory structures and bypass of much of the ciliary escalator occur in infants who require endotracheal intubation. In these infants, increased physical disruption of epithelial and mucous barriers also occurs. In addition, interventional exposure to high oxygen concentrations, excessive airway pressures, and large intrapulmonary gas volumes may interfere with ciliary function and mucosal integrity.

Secretory antibodies and mucosal lymphoid tissue are absent or minimally functional for the first month of life postnatally. Systemic antibodies may enter pulmonary tissues but usually consist primarily of passively transmitted maternal antibodies, with reduced transplacental transport of maternal antibodies before 32 weeks' gestation. Specific systemic antibodies can be generated, but the many components of the necessary immunologic machinery are relatively sluggish.

Circulating complement components are present at approximately 50% of the concentration found in older children, although components of the alternative pathway are present in sufficient quantities to serve as effective opsonins.

The neonatal granulocyte number frequently decreases in response to early infection, whereas the phagocytes that are present often move much more sluggishly to the inflammatory focus, whether it is a microorganism or inanimate debris. Once at the targeted sites, phagocytes often ingest the invaders less efficiently, although intracellular microbicidal activities appear normal. Intercellular communication via cytokines and other mediators is blunted.

The net result of these and other developmental aberrations is that the fetal and neonatal inflammatory response is slower, less efficient, and much less focused than in older children. Infection is less likely to be localized and effectively inhibited by host defenses alone. Inflammation from particulate debris and other foreign substances is isolated less effectively and the injurious effector portions of the inflammatory cascade are targeted much less finely.

Pathogenesis

In neonatal pneumonia, pulmonary and extrapulmonary injuries are caused directly and indirectly by invading microorganisms or foreign material and by poorly targeted or inappropriate responses by the host defense system that may damage healthy host tissues as badly or worse than the invading agent. Direct injury by the invading agent usually results from synthesis and secretion of microbial enzymes, proteins, toxic lipids, and toxins that disrupt host cell membranes, metabolic machinery, and the extracellular matrix that usually inhibits microbial migration.

Indirect injury is mediated by structural or secreted molecules, such as endotoxin, leukocidin, and toxic shock syndrome toxin-1, which may alter local vasomotor tone and integrity, change the characteristics of the tissue perfusate, and generally interfere with the delivery of oxygen and nutrients and removal of waste products from local tissues.

The activated inflammatory response often results in targeted migration of phagocytes, with the release of toxic substances from granules and other microbicidal packages and the initiation of poorly regulated cascades (eg, complement, coagulation, cytokines). These cascades may directly injure host tissues and adversely alter endothelial and epithelial integrity, vasomotor tone, intravascular hemostasis, and the activation state of fixed and migratory phagocytes at the inflammatory focus. The role of apoptosis (noninflammatory programmed cell death) in pneumonia is poorly understood.

On a macroscopic level, the invading agents and the host defenses both tend to increase airway smooth muscle tone and resistance, mucous secretion, and the presence of inflammatory cells and debris in these secretions. These materials may further increase airway resistance and obstruct the airways, partially or totally, causing airtrapping, atelectasis, and ventilatory dead space. In addition, disruption of endothelial and alveolar epithelial integrity may allow surfactant to be inactivated by proteinaceous exudate, a process that may be exacerbated further by the direct effects of meconium or pathogenic microorganisms.

In the end, conducting airways offer much more resistance and may become obstructed, alveoli may be atelectatic or hyperexpanded, alveolar perfusion may be markedly altered, and multiple tissues and cell populations in the lung and elsewhere sustain injury that increases the basal requirements for oxygen uptake and excretory gas removal at a time when the lungs are less able to accomplish these tasks.

Alveolar diffusion barriers may increase, intrapulmonary shunts may worsen, and ventilation-perfusion mismatch may further impair gas exchange despite endogenous homeostatic attempts to improve matching by regional vasoconstriction or bronchoconstriction. Because the myocardium has to work harder to overcome the alterations in pulmonary vascular resistance that accompany the above changes of pneumonia, the lungs may be less able to add oxygen and remove carbon dioxide from mixed venous blood for delivery to end organs. The spread of infection or inflammatory response, either systemically or to other focal sites, further exacerbates the situation.

Frequency

International

Congenital pneumonia frequently occurs in newborn infants, although reported rates vary considerably depending on the diagnostic criteria used and the characteristics of the population under study. Most reports cite frequencies in the range of 5-50 per 1000 live births, with higher rates in the settings of maternal chorioamnionitis, prematurity, and meconium in the amniotic fluid.

Mortality/Morbidity

• Determination of mortality rates among infants with congenital pneumonia is complicated by variations in diagnostic criteria. Among infants with congenital pneumonia associated with proven blood-borne infection, mortality is in the range of 5-10%, with rates as high as 30% in infants with very low birth weight.
• Pneumonia is a contributing factor in 10-25% of all deaths that occur in neonates younger than 30 days.

Race

No increased risk associated with race or ethnic group has been well documented.

Sex

No increased risk associated with sex has been well documented.

Age

Congenital pneumonia can occur at any gestational age associated with potential extrauterine survival.

Clinical

History

Diagnostic criteria remain controversial in the absence of histopathologic specimens. Criteria range from very liberal (to minimize the probability of missing a case) to very stringent (to minimize the possibility of labeling some other condition inappropriately). An example of the former includes only respiratory difficulties and persistent radiographic evidence of infiltrates. More stringent standards often mandate the additional presence of laboratory markers of systemic inflammation and inflammatory respiratory secretions (using quantitative or semiquantitative threshold criteria). Diagnosis in the clinical setting is usually based on a combination of historical, physical, radiographic, microbiologic, and laboratory findings.

• Prenatal features that suggest an increased risk for congenital pneumonia include the following:
  • Unexplained preterm labor
  • Rupture of membranes before the onset of labor
  • Membrane rupture more than 18 hours before delivery
  • Maternal fever (>38°C/100.4°F)
  • Uterine tenderness
  • Foul-smelling amniotic fluid
  • Infection of the maternal genitourinary tract
  • Previous infant with neonatal infection
  • Nonreassuring fetal well-being test results
  • Fetal tachycardia
  • Meconium in the amniotic fluid
  • Recurrent maternal urinary tract infection
  • Gestational history of illness consistent with an organism known to have transplacental pathogenic potential
• Review antenatal screening tests for infection, such as serologic tests for syphilis and birth canal tests for Neisseria gonorrhoeae, Chlamydia species, or group B Streptococcus, as well as any treatment courses and testing for cure.
• Intrapartum antibiotic therapy reduces the risk of postpartum maternal infection and infection of the infant in the presence of some of these risk factors but does not eliminate the risk. The potential for selection of pathogens resistant to antibiotics used for intrapartum therapy remains controversial.
• Absence of these risk factors does not exclude pneumonia.

Physical

Physical findings may be pulmonary, systemic, or localized. Many extrapulmonary findings are nonspecific and may be seen in many other common neonatal conditions. Some signs of respiratory distress cannot be manifested if the infant is affected by other processes that result in apnea, such as poor tolerance of labor, exposure to transplacental respiratory depressants, or CNS anomaly or injury.

• Pulmonary findings - All findings not necessarily present in all affected infants
  • Tachypnea (respiratory rate >60/min) may be present.
  • Expiratory grunting may occur.
  • Accessory respiratory muscle recruitment, such as nasal flaring and retractions at subcostal, intercostal, or suprasternal sites, may occur.
  • Airway secretions may vary substantially in quality and quantity but are most often profuse and progress from serosanguineous to a more purulent appearance. White, yellow, green, or hemorrhagic colors and creamy or chunky textures are not infrequent.
  • If aspiration of meconium, blood, or other proinflammatory fluid is suspected, other colors and textures reflective of the aspirated material may be seen.
  • Rales, rhonchi, and cough are all observed much less frequently in infants with pneumonia than in older individuals. If present, they may be caused by noninflammatory processes, such as congestive heart failure, condensation from humidified gas administered during mechanical ventilation, or endotracheal tube displacement. Although alternative explanations are possible, these findings should prompt careful consideration of pneumonia in the differential diagnosis.
  • Cyanosis of central tissues, such as the trunk, implies a deoxyhemoglobin concentration of approximately 5 g/dL or more and is consistent with severe derangement of gas exchange from severe pulmonary dysfunction as in pneumonia, although congenital structural heart disease, hemoglobinopathy, polycythemia, and pulmonary hypertension (with or without other associated parenchymal lung disease) must be considered.
  • Infants may have external staining or discoloration of skin, hair, and nails with meconium, blood, or other materials when they are present in the amniotic fluid. The oral, nasal, and, especially, tracheal presence of such substances is particularly suggestive of aspiration.
  • Increased respiratory support requirements such as increased inhaled oxygen concentration, positive pressure ventilation, or continuous positive airway pressure are commonly required before recovery begins.
  • Infants with pneumonia may manifest asymmetry of breath sounds and chest excursions, which suggest air leak or emphysematous changes secondary to partial airway obstruction.
• Systemic findings - Similar to signs and symptoms seen in sepsis or other severe infections
  • Temperature instability
  • Skin rash
  • Jaundice at birth
  • Tachycardia
  • Glucose intolerance
  • Abdominal distention
  • Hypoperfusion
  • Oliguria
• Localized findings
  • Conjunctivitis
  • Vesicles or other focal skin lesions
  • Unusual nasal secretions
  • Erythema, swelling, growth, unusual drainage, or asymmetry of other structures suggestive of inflammation
• Other findings
  • Adenopathy suggests long-standing infection and should suggest a more chronic causative agent.
  • Hepatomegaly from infection may result from the presence of some chronic causative agents, cardiac impairment, or increased intravascular volume. Apparent hepatomegaly may result if therapeutic airway pressures result in generous lung inflation and downward displacement of a normal liver.

Causes

Pneumonia that becomes clinically evident within 24 hours of birth may originate at 3 different times. The 3 types often overlap, and assigning a particular pneumonic episode to one of these categories may be difficult. The 3 categories of congenital pneumonia are: (1) true congenital pneumonia, (2) intrapartum pneumonia, and (3) postnatal pneumonia. Not all pneumonia diagnosed in the first 24 hours of life is infectious; nonetheless, many cases are infectious and benefit from targeted antimicrobial therapy.

True congenital pneumonia

• True congenital pneumonia is already established at birth. True congenital pneumonia may be established long before birth or relatively shortly before birth.
• The infant has clinical signs of pneumonia almost immediately after birth. Further deterioration is frequent as the process progresses and the infant is confronted with the exigencies of adapting to extrauterine existence.
• If the infant tolerated labor poorly or has been exposed to agents that depress respiratory effort, the infant may initially be apneic, with no ability to manifest signs of respiratory distress.
• Transmission of congenital pneumonia usually occurs via 1 of 3 routes:
  • Hematogenous transmission
    • If the mother has a bloodstream infection, the microorganism can readily cross the few cell layers that separate the maternal from the fetal circulation at the villous pools of the placenta.
    • The mother may be febrile or have other signs of infection, depending on the integrity of her host defenses, the responsible organism, and other considerations.
    • Transient bacteremia following daily activities, such as brushing teeth, defecating, and other potential disruptions of colonized mucoepithelial surfaces, is well known and may result in transmission without significant maternal illness.
    • The likelihood of hematogenous transmission is increased if the mother has continuous bloodstream infection with a relatively large quantity of microorganisms. In this case, the mother is more likely to have suggestive signs and symptoms.
    • Because host defenses are limited in fetuses, dissemination and illness may result. The fetus is likely to have systemic disease.
  • Ascending transmission: Ascending infection from the birth canal and aspiration of infected or inflamed amniotic fluid have significant common features. Infected amniotic fluid often involves ascending pathogens from the birth canal but may result from hematogenous seeding or direct introduction during pelvic examination, amniocentesis, placement of intrauterine catheters, or other invasive procedures. Ascension may occur with or without ruptured amniotic membranes.
  • Transmission via aspiration: Most bacterial infections produce clinical signs of infection in the mother, but infections may not be evident if the membranes rupture shortly after inoculation, similar to drainage of an abscess. Some nonbacterial organisms, such as Ureaplasma urealyticum, may be present in the amniotic cavity for long periods and cause minimal symptoms in the mother. If the fetus aspirates infected fluid prior to delivery, organisms that reach the distal airways or alveoli may need to cross only 2 cell layers (alveolar epithelium, capillary endothelium) to enter the bloodstream. Typically, these infants present with more pulmonary than systemic signs, but this is not always the case.

Intrapartum pneumonia

• Intrapartum pneumonia is acquired during passage through the birth canal.
• Intrapartum pneumonia may be acquired via hematogenous or ascending transmission, or it may result from aspiration of infected or contaminated maternal fluids or from mechanical or ischemic disruption of a mucosal surface that has been freshly colonized with a maternal organism of appropriate invasive potential and virulence.
• Infants who aspirate proinflammatory foreign material, such as meconium or blood, may manifest pulmonary signs immediately after or very shortly after birth.
• Infectious processes often have a honeymoon period of a few hours before sufficient invasion, replication, and inflammatory response have occurred to cause clinical signs.

Postnatal pneumonia

• Postnatal pneumonia in the first 24 hours of life originates after the infant has left the birth canal.
• Postnatal pneumonia may result from some of the same processes described above, but infection occurs after the birth process.
• Colonization of a mucoepithelial surface with an appropriate pathogen from a maternal or environmental source and subsequent disruption allows the organism to enter the bloodstream, lymphatics, or deep parenchymal structures.
• The frequent use of broad-spectrum antibiotics encountered in many obstetrical services and neonatal intensive care units (NICUs) often results in predisposition of an infant to colonization by resistant organisms of unusual pathogenicity. Invasive therapies typically required in these infants often allow microbes accelerated entry into deep structures that ordinarily are not easily accessible.
• Enteral feedings may result in aspiration events of significant inflammatory potential. Indwelling feeding tubes may further predispose infants to gastroesophageal reflux and other aspiration events. These infants are often relatively asymptomatic at birth or manifest noninflammatory pulmonary disease consistent with gestational age, but develop signs that progress well after 24 hours.

Other types of pneumonia

• Noninfectious pneumonia: This may occur in the first 24 hours of life.
• Infectious pneumonia
  • Organisms responsible for infectious pneumonia typically mirror those responsible for early onset neonatal sepsis. This is not surprising in view of the role that maternal genitourinary and gastrointestinal tract flora play in both processes. Group B Streptococcus was the most common bacterial isolate in most locales from the late 1960s to the late 1990s, when the impact of intrapartum chemoprophylaxis in reducing neonatal and maternal infection by this organism became evident. Escherichia coli has become the most common bacterial isolate among very low birth weight infants (£ 1500 g) since that time. Other prominent bacterial organisms include the following:
    • Nontypeable Haemophilus influenzae
    • Other gram-negative bacilli
    • Listeria monocytogenes
    • Enterococci
    • Occasionally, Staphylococcus aureus
  • Among nonbacterial potential pathogens, U urealyticum has been recovered quite frequently from endotracheal aspirates shortly after birth in infants with very low birth weight and has been associated with various adverse pulmonary outcomes, including bronchopulmonary dysplasia. However, whether this organism is causal or simply a marker of increased risk is unclear.
  • Agents of chronic congenital infection, such as cytomegalovirus, Treponema pallidum, Toxoplasma gondii, and others, may cause pneumonia in the first 24 hours of life. Clinical presentation usually involves other organ systems as well.
  • Chlamydia organisms presumably are transmitted at birth during passage through an infected birth canal, although most infants are asymptomatic during the first 24 hours and develop pneumonia only after the first 2 weeks of life.
  • Respiratory pathogens, such as respiratory syncytial virus, influenza, adenovirus, and others, may be transmitted by contact with infected family members or caregivers shortly after birth, but infection by these organisms rarely is becomes apparent during the first 24 hours.

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