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

Apnea of Prematurity: Differential Diagnoses & Workup

Author: Dharmendra J Nimavat, MD, FAAP, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine
Coauthor(s): Michael P Sherman, MD, Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Director, Fellowship Training Program in Neonatal-Perinatal Medicine, NICU, Columbia Regional Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine; Rene L Santin, MD, Consulting Staff, Department of Pediatrics, Division of Neonatology, Primary Care Centers of Eastern Kentucky; Rachel Porat, MD, Director, Neonatal Apnea Monitoring Program, Assistant Director, Division of Neonatology, Albert Einstein Medical Center; Associate Professor, Department of Pediatrics, Thomas Jefferson University
Contributor Information and Disclosures

Updated: Oct 26, 2009

Differential Diagnoses

Anemia of Prematurity
Neonatal Sepsis
Respiratory Failure
Respiratory Syncytial Virus Infection

Other Problems to Be Considered

Apnea of prematurity (AOP) is a diagnosis of exclusion. For many diseases in preterm infants, apnea is a presenting symptom. The causes of these diseases are different when the differential diagnosis occurs shortly after birth compared with later in the patient's hospital stay. Other etiologies must be sought before drug and/or ventilatory therapies for apnea of prematurity are started.

Conditions Associated with Apnea

Shortly after birth, apnea can be a manifestation of several types of conditions:

  • Respiratory distress syndrome and other pulmonary conditions
  • Infections (eg, congenital pneumonia, bacteremia, meningitis, fetal or neonatal inflammatory response syndrome)
  • Hypoglycemia and other metabolic diseases
  • CNS pathology (eg, trauma, intracranial hemorrhage, anoxia and/or ischemia, stroke)

The aforementioned brain insults may be noticed because patients may have seizures and/or associated apnea.65,54 Some of the diseases cited above also occur relatively late during the hospitalization of prematurely born infants, but the signs and symptoms may or may not include apnea.

Intraventricular hemorrhage and posthemorrhagic hydrocephalus without seizures increases the frequency of apnea in preterm infants.53,66

Other Conditions Associated with Apnea in Preterm Infants During Hospitalization

Other conditions associated with apnea in preterm infants during their hospitalization are summarized below.

Nosocomial bacterial or fungal infection

Apnea, bradycardia, and desaturations are presenting symptoms of nosocomial infections caused by bacteria and fungi or viral agents.67,68

In a study of 9 infants in an NICU who had respiratory syncytial viral infection, 8 had apnea as a manifestation of disease.69

Apnea is also common in preterm infants with Ureaplasma urealyticum infection.70

Necrotizing enterocolitis

In addition, apnea is one of several signs and symptoms associated with the onset of necrotizing enterocolitis.71

Exposure to magnesium

The administration of magnesium to prevent seizures in preeclampsia and tocolysis of preterm labor has been associated with hypoventilation, apnea, and other adverse effects in preterm infants.72 Hypermagnesemia during parenteral nutrition has also been a cause of apnea.73

Anemia

Disagreement exists regarding the role of clinically significant anemia in the development of apnea among convalescing preterm infants. Westkamp and colleagues reported that blood transfusions lowered heart and respiratory rates but had little effect on apnea of prematurity.74 Bell and associates conversely found that liberal versus restrictive blood transfusion significantly reduced apnea.75 The recent interest in the adverse neurodevelopmental outcomes observed in preterm infants with anemia and low iron status emphasizes neonatology-related awareness of the problem.76

Surgery

Postoperative apnea occurs in preterm infants, particularly those whose intraoperative pain relief involved general anesthesia.77,78

Additional research is required to determine whether spinal anesthesia, different analgesic agents, or caffeine can mitigate morbidity associated with apnea after surgery in prematurely born infants.79,80

Immunization

Apnea transiently increases or recurs in hospitalized preterm infants after immunization. The increase in apnea has been attributed to the whole-cell pertussis component.81 Investigators have observed reduced morbidity with newer vaccines that contain acellular pertussis.82,83 Some recent reports still identified clinically significant apnea and other adverse events.84,85

Gastroesophageal reflux

As stated earlier, controversy exists regarding the role of gastroesophageal reflux (GER) as a causative factor in apnea of prematurity.9 One perspective is that the 2 conditions are related.63,86 Laryngeal edema identified during fiberoptic laryngeal endoscopy has been associated with GER, and antireflux surgery has dramatically reduced apnea in preterm infants at highest risk.87,88,89

Past and recent research failed to reveal a temporal relationship between GER and apnea of prematurity.47,90,91,92,48

Therefore, the NICHD Review Group on Apnea of Prematurity has called for additional investigations with rigorous research designs.9

Skin-to-skin contact, or kangaroo care

Skin-to-skin contact, or kangaroo care, for preterm infants has been associated with an increased occurrence of apnea, bradycardia, and desaturation; this appears to be unrelated to hyperthermia.93,94 The observation suggests that obstructive events may occur during skin-to-skin contact. These findings call attention to the importance of environmental hyperthermia as a cause of apnea in preterm infants.95,96

Recent investigators found no adverse events during kangaroo care.97

The disparity among the reported studies may be related to the specific practice of skin-to-skin care in a particular NICU or the validity of monitoring during skin-to-skin contact.98

Workup

Laboratory Studies

  • A CBC count and cultures of blood, urine, and spinal fluid are necessary if a serious bacterial or fungal infection is suspected in patients with apnea of prematurity (AOP).
    • Appropriate viral cultures or collection of body fluid for polymerase chain reaction (PCR) analyses are performed if a viral pathogen was suspected.
    • A C-reactive protein level measured at 36-48 hours after birth may be useful for excluding infection (see Maternal Chorioamnionitis).
  • Tests for ammonia, amino acid profiles in blood or urine, and organic acid levels in blood and urine are essential if a metabolic disorder is suspected.
    • Testing of pyruvate and lactate concentrations in the blood and cerebrospinal fluid (CSF) may be diagnostically helpful when inborn errors of metabolism are among the differential diagnosis.
    • Ketones in the urine may indicate organic acidemia.
  • Serum electrolyte, calcium, magnesium, and glucose levels can be useful for diagnosing a recent stressful condition, a metabolic process, or chronic hypoventilation.
  • Analysis of the stool for different toxins related to botulism may reveal a cause in an infant with apnea, constipation, clinically significant hypotonia, difficulty swallowing or crying, or absent eye movements.99

Imaging Studies

  • Chest radiography and/or a nuclear medicine milk scanning can be helpful if the child has persistent but unexplained lower airway symptoms (eg, wheezing and/or repetitive regurgitation after feeding, rumination).100
  • In cases of airway obstruction, stridor, or unexplained pathologic obstructive apnea, helpful upper airway evaluations include lateral neck radiography, head and neck 3-dimensional tomography, and otolaryngologic evaluation (eg, fiberoptic assessment of the larynx through the nose during spontaneous breathing).101
  • Imaging studies of intracranial pathology are necessary when hemorrhage is suspected or when findings include dysmorphic facial and somatic features, abnormal neurologic results, disordered hair whorls, and/or mental status changes.
  • A barium swallow study is useful if the infant has signs of swallowing dysfunction or anatomic anomalies (eg, an esophageal web, tracheoesophageal fistula).
  • A gastric-emptying study and abdominal sonography are useful in patients whose clinical picture includes a generalized GI motility disorder or pyloric stenosis.

Other Tests

  • Obtain a polysomnographic, or continuous multichannel, recording to measure the chest-wall movement, nasal and/or oral airflow (or change in air temperature), O2 saturation, and heart rate trend. A 2-channel pneumogram that is used to measure only chest-wall excursion and trends in heart rate provides insufficient information. The following results are diagnostic:
    • Central apnea - Absence of nasal airflow and wall movement
    • Obstructive apnea - Lack of airflow despite chest-wall movement
    • Mixed apnea - Combined results of central and obstructive apnea
  • If gastroesophageal reflux (GER) is suspected, note the intraesophageal pH as part of the multichannel recording.
  • Consider obtaining an electroencephalogram (EEG) in infants who have suspected apneic seizures or who have persistent pathologic central apnea without an identifiable cause.
  • Obtain an echocardiogram and consult a cardiologist if the patient's history or physical findings (eg, feeding difficulties, heart murmur, cyanosis) suggest cardiac disease.
  • ECG results are useful in patients with severe unexplained tachycardia or bradycardia. Abnormalities in cardiac conduction (eg, prolonged-QT syndrome) are infrequent but important causes of apnea during infancy.
  • Evaluate patients for unilateral choanal stenosis and choanal atresia by passing a small-diameter feeding tube through both nares. Three-dimensional tomography is probably the method of choice for definitively diagnosing upper airway malformations.

Procedures

  • Several studies may reveal diagnostic findings in selected infants. These include fiberoptic examination of the larynx through the nose during spontaneous breathing, direct laryngoscopy, and bronchoscopy (which is usually performed with the patient under anesthesia).
  • Emergency or scheduled tracheostomy may be used to manage severe airway obstruction caused by a number of conditions.
    • Tracheostomy might occur after the airway is stabilized by using endotracheal intubation.
    • Jaw-distraction surgery was recently used to avoid tracheostomy in neonatal conditions (eg, Robin sequence) that involve severe micrognathia as a component of malformation.102,103

More on Apnea of Prematurity

Overview: Apnea of Prematurity
Differential Diagnoses & Workup: Apnea of Prematurity
Treatment & Medication: Apnea of Prematurity
Follow-up: Apnea of Prematurity
Multimedia: Apnea of Prematurity
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

apnea of prematurity, AOP, fetal breathing, pathologic apnea, central apnea, obstructive apnea, mixed apnea, apnea of infancy, AOI, neonatal apnea, sudden infant death syndrome, SIDS, crib death, cot death

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Contributor Information and Disclosures

Author

Dharmendra J Nimavat, MD, FAAP, Assistant Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine
Dharmendra J Nimavat, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics and American Association of Physicians of Indian Origin
Disclosure: Nothing to disclose.

Coauthor(s)

Michael P Sherman, MD, Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Director, Fellowship Training Program in Neonatal-Perinatal Medicine, NICU, Columbia Regional Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine
Michael P Sherman, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Microbiology, European Society for Paediatric Research, Perinatal Research Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Rene L Santin, MD, Consulting Staff, Department of Pediatrics, Division of Neonatology, Primary Care Centers of Eastern Kentucky
Disclosure: Nothing to disclose.

Rachel Porat, MD, Director, Neonatal Apnea Monitoring Program, Assistant Director, Division of Neonatology, Albert Einstein Medical Center; Associate Professor, Department of Pediatrics, Thomas Jefferson University
Rachel Porat, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Medical Editor

Steven M Donn, MD, Professor of Pediatrics, University of Michigan Medical School; Director, Division of Neonatal-Perinatal Medicine, Department of Pediatrics, CS Mott Children's Hospital, University of Michigan Health System
Steven M Donn, MD is a member of the following medical societies: American Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Arun K Pramanik, MD, MBBS, Professor of Pediatrics, Director of Neonatal Fellowship, Louisiana State University Health Sciences Center
Arun K Pramanik, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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