What Causes Apnea in a Premature Infant?

Patient Presentation
A 1 week-old, 34-week gestation female began having apnea and feeding intolerance.
The past medical history showed a normal pregnancy until there was spontaneous rupture of membrances and contractions. She was delivered after 20 hours of labor.
She had no respiratory distress and had Apgar scores of 8 and 8.
Postnatally, she had hyperbilirubinemia that was treated with phototherapy. After her initial complete blood count revealed a normal white blood cell count of 4.6 x 1000/mm2 but neutrophils of 75%, she was begun on antibiotics which were discontinued after 3 days when the cultures were negative.
She was begun on oral/nasogastric feeds on day 2 of life which she tolerated. She was slowly advancing on her feedings when the nursing staff noticed that she was having some apneic spells that lasted 25-30 seconds. These responded initially to blow-by oxygen and stimulation. She then had a large gastric aspirate and her abdomen appeared distended on day of life 7.
The pertinent physical exam showed heart rate of 182, respiratory rate of 63 and blood pressure of 82/54 with appropriate for gestatation growth. There was a distended abdomen with no overlying erythema or organomegaly.
During the examination, she passed a stool that appeared to have blood in it and later was found to be hemoccult positive. As she was being evaluated and treated she had more apnea that responded to nasal continuous positive airway pressure.
The laboratory evaluation included an arterial blood gas that showed mild metabolic acidosis. The complete blood count showed a white blood cell count of 14.8 x 1000/mm2 with 80% neutrophils. The platelets were normal. The C-reactive protein was slightly elevated at 2.2 mg/dl.
The radiologic evaluation included an abdominal flat plate and cross-table lateral which showedthickened and dilated bowel loops in teh abdomen with a question of pneumatosis intestinalis. There was no free air in the abdomen or the portal system.
The diagnosis of necrotizing enterocolitis was made. Her feedings were stopped and she was begun on Gentamicin, Clindamycin and Ampicillin. She slowly improved with medical treatment and did not require surgery. On day 14 after the initial presentation, she was begun on enteral feedings that were slowly advanced.
The rest of her nursery stay was uncomplicated and she was discharged at 5 weeks of age.

Figure 34 – Supine AP radiograph of the abdomen shows dilated loops of bowel centered in the right lower quadrant. This alone can suggest early and developing necrotizing enterocolitis. There was a question of pneumatosis intestinalis within these dilated loops of bowel.

Necrotizing enterocolitis (NEC) is one of the most common gastrointestinal emergencies in neonates. Mortality rates are from 0-45% depending on infant weight and gestation. Infants < 1000 g have mortality rates of 40-100%.
NEC usually occurs in premature infants but it also occurs in term infants. The etiology is unknown but is probably multifactorial with ischemia and/or reperfusion playing some role.
There are ‘outbreaks’ of NEC but no causitive organism has been identified. Regardless of the originating cause, inflammation of the intestine and release of inflammatory mediators causes various degrees of damage to the intestine.
Treatment includes stopping gastric feeding, antibiotics, possible surgery and other supportive measures such as treatment for hypotension and respiratory failure.

Presenting signs of NEC can be subtle but can include:

  • Feeding intolerance
  • Delayed gastric emptying – i.e. residual feeding left in the stomach
  • Apnea
  • Abdominal distention and/or tenderness
  • Bleeding diathesis
  • Blood in the stool – obvious or occult
  • Decreased bowel sounds – i.e. ileus
  • Erythema of the abdominal wall
  • Lethargy
  • Poor perfusion
  • Shock

Abnormalities on laboratory testing are nonspecific but can include:

  • Hyponatremia
  • Metabolic acidosis
  • Leukopenia
  • Leukocytosis with left shift
  • Neutropenia
  • Thrombocytopenia
  • Bleeding test abnormalities including prolonged prothrombin time, prolonged activated partial thromboplastin time, decreased fibrinogen and increased fibrin split products

Learning Point
Apnea is defined as a cessation of breathing for more than 20 seconds. It is often associated with bradycardia, cyanosis or both.

The most common cause of apnea in premature infants is apnea of prematurity where the mechanisms that usually ensure cerebral blood flow fail and hypoxemia, ischemia and possibly other complications may arise.
During apneic spells, blood is diverted away from the mesenteric arteries to try to preserve cerebral blood flow. This can cause intestinal ischemia and possibly NEC.

Other causes of apnea in premature infants includes:

  • Cardiac
    • Congestive heart failure
    • Cyanotic congenital heart disease
    • Pulmonary edema
  • Gastrointestinal
    • Gastroesophageal reflux
    • NEC
  • Hematologic
    • Anemia
  • Infectious
    • Perinatal infection/sepsis – especially on day of life 1
    • Nosocomial infection
    • Pneumonia
  • Medication
    • Prenatal – transplacental transfer, e.g. narcotics, beta-blockers
    • Postnatal – e.g. hypnotics, narcotics, sedatives
  • Metabolic
    • Acidosis
    • Hypocalcemia
    • Hypoglycemia
    • Hyponatremia
  • Neurologic
    • Increased intracranial pressure
    • Intracranial hemorrhage
    • Intraventricular hemorrhage
    • Perinatal asphyxia
    • Seizures
  • Pulmonary
    • Meconium aspiration
    • Surfactant deficiency
  • Other
    • Unstable temperature

Questions for Further Discussion
1. What evaluation should be completed for a newborn infant with apnea?
2. What causes bradycardia in infants?
3. What are some of the possibilities for surgical treatment for NEC?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MEDLINEplus for this topic: Premature Babies

To view current news articles on this topic check Google News.

Klein J. Management of Neonatal Apnea. Iowa Neonatology Handbook.
Available from the Internet at http://www.uihealthcare.com/depts/med/pediatrics/iowaneonatologyhandbook/pulmonary/managementapnea.html (rev. 1/2006, cited 1/30/2006).

Springer, SC. Annibale DJ. Necrotizing Enterocolitis. eMedicine.
Available from the Internet at http://www.emedicine.com/ped/topic2601.htm (rev. 11/25/2002, cited 1/30/2006).

ACGME Competencies Highlighted by Case

  • Patient Care
    2. Essential and accurate information about the patients is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    7. All medical and invasive procedures considered essential for the area of practice are competency performed.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.

  • Interpersonal and Communication Skills
    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

    Donna M. D’Alessandro, MD
    Associate Professor of Pediatrics, Children’s Hospital of Iowa

    February 27, 2006