Respiratory problems in a newborn:
When the grunting and flaring won't go away

By Brian K. Crownover, MD

Respiratory signs and symptoms in newborns may reflect the normal transition from prenatal to postnatal breathing—or a problem that requires treatment or referral. A systems-based approach will help you recognize true respiratory distress and keep evaluation and management on track.

 

K. C. is a newborn girl born at 41 weeks' gestation by spontaneous vaginal delivery. Her antenatal course was unremarkable. Labor progressed normally, and she was delivered and passed to the delivery room nurse after 15 minutes of pushing by the mother. Apgar score was 8 at one minute and five minutes of life. The initial physical exam was normal except for acrocyanosis and moderate grunting and flaring. A repeat exam at 20 minutes of life reveals persistent grunting. The baby's respiratory rate is 60/min, and her arterial oxygen saturation (SAO2) is 95% as measured by pulse oximetry. Her heart rate is 160/min. Is it safe to continue observing this newborn, or does she require intervention now?

Neonatal respiratory problems may present early, suddenly, and unexpectedly. Physicians who provide perinatal care must be able to distinguish normal respiratory transition from true distress requiring intervention or referral. They should be well-versed in the protocols of the American Academy of Pediatrics' Neonatal Resuscitation Program (NRP).¹

After initial stabilization, subsequent management of the sick newborn becomes more complex and less well-defined. Neonatal respiratory problems merit special attention in light of the finding of one study that respiratory distress was the cause of 79% of transfers of sick newborns from community hospitals to neonatal intensive care units.² This article presents a systems-oriented approach to initial diagnosis and management of respiratory problems in the term and near-term newborn.* Management of preterm infants less than 36 weeks of age is outside the scope of this discussion.

*A search was conducted of several evidence-based Web sites, including the National Guideline Clearinghouse, Bandolier, the Agency for Healthcare Research and Quality, the British Medical Journal Clearinghouse, the Cochrane Database, and the British National Health Service.³ In addition, a PubMed search for "respiration disorders" was performed using the following limits: publication type—randomized controlled trial; age—newborn; languages—English; and human. A total of 616 abstracts were retrieved and reviewed.

Normal respiratory transition

Respiratory transition from prenatal to postnatal life involves removal of lung fluid and aeration of previously closed alveoli. This process is aided by surfactant, which lines the alveolar surfaces, reduces the surface tension, and lowers the inspiratory pressures required to open the alveoli.⁴ The average pressure required to open the alveoli is 10 to 20 cm H₂O, but 50 cm H₂O may be required in the diseased lung of a term infant.⁴ Most neonatal ventilation bags are equipped with a pressure release pop-off valve set at 30 to 40 cm H₂O to avoid overdistention and iatrogenic barotrauma.⁵

During the first 20 minutes of life, certain respiratory findings may be present that are considered normal variants but become worrisome if they persist. A heart rate of 160/min to 180/min, irregular respirations, and a respiratory rate of 60/min to 80/min may occur.² Inspiratory retractions, grunting, and flaring also may be seen. Observation can continue without intervention if the newborn remains alert, cries appropriately when stimulated, and maintains good color and good tone. By 20 minutes of life, the respiratory rate should be fewer than 60/min, the pulse should be fewer than 160/min, and arterial oxygen saturation (SAO₂) should be greater than 90%. Table 1 defines signs and symptoms associated with respiratory transition.

 

TABLE 1 Signs and symptoms associated with respiratory transition in newborns
Sign	Definition
Neonatal tachypnea	Respiratory rate >60/min
Apnea	Respiratory pause >20 sec or any pause accompanied by cyanosis and bradycardia
Central cyanosis	Bluish color of central trunk, lips, and mucous membranes
Grunting	Audible moan, whimper, or cry during expiration
Nasal flaring	Widening of the nostrils during inspiration
Retractions	Sinking of skin above the clavicles (supraclavicular), between the ribs (intercostal), or below the sternum (substernal) during inspiration
Source: Kattwinkel J (ed)1

Do not confuse apnea, which is always considered an abnormal finding, with periodic breathing. During sleep in the first weeks of life, normal term infants can have pauses in respiration lasting 10 to 15 seconds. These pauses may be followed by bursts of rapid breathing (60 breaths a minute) for 10 to 15 seconds. Periodic breathing is differentiated from apnea by maintenance of normal heart rate and color and respiratory pauses that last fewer than 20 seconds. Periodic breathing is considered physiologic and has no prognostic significance.⁴ In contrast, apnea spells are defined as respiratory pauses longer than 20 seconds or any pause accompanied by bradycardia or cyanosis.

Pediatricians should always anticipate potential respiratory problems when attending a delivery, and be prepared to address them. Table 2 lists risk factors for neonatal respiratory problems and their mechanism of action. The history of any newborn who exhibits respiratory signs and symptoms should include questions about these risks.

 

TABLE 2 Risk factors for neonatal respiratory problems
Risk factor	Mechanism
Prematurity	Overcompliant chest wall cannot generate sufficient ventilatory pressures Surfactant deficiency; correlates inversely with gestational age
Diabetic mother	Delayed lung maturity
Caesarean delivery	Delayed lung fluid absorption because the infant was not compressed passing through the birth canal
Fetal distress	Associated with meconium aspiration syndrome
Meconium	Aspirated meconium fills the alveoli and decreases benefits of surfactant Pre-existing asphyxia exacerbates insult from meconium
Cold stress/hypothermia	Decreased surfactant production
Maternal narcotic analgesia	Decreased neonatal respiratory effort and functional residual capacity
Maternal colonization with group B Streptococcus	Pneumonia, sepsis, or meningitis

Differential diagnosis of respiratory problems

A systems-based approach to the diagnosis of neonatal respiratory problems can help organize evaluation decisions. Table 3 presents a comprehensive list of diagnoses to consider. Pulmonary and cardiovascular diagnoses in particular deserve further discussion.

 

TABLE 3 A glimpse at the broad differential diagnosis of neonatal respiratory problems
System	Diagnosis
Upper respiratory	Nasal: choanal atresia, craniofacial midface hypoplasias Oral: Robin syndrome (macroglossia, micrognathia) Neck: goiter, cystic hygroma Laryngeal: laryngomalacia, hemangioma, supraglottic cysts and webs, cord paralysis, subglottic stenosis Tracheal: trachealesophageal fistula, tracheomalacia
Lower respiratory	Pneumonia: Group B Streptococcus, Listeria, coliforms, cytomegalovirus, rubella, herpes simplex virus, Chlamydia Meconium aspiration Blood aspiration Amniotic fluid aspiration Transient tachypnea of the newborn Air leak: pneumothorax, pneumomediastinum, pulmonary interstitial emphysema Respiratory distress syndrome
Cardiovascular	Congenital heart disease Persistent pulmonary hypertension of the newborn Hypotension/volume loss
Gastrointestinal	Diaphragmatic hernia
Central nervous	Intracranial hemorrhage Meningitis Hypoxic-ischemic insult Primary seizure disorders Neuromuscular disorders
Metabolic	Hypothermia Hypoglycemia Hypocalcemia Metabolic acidosis (any source) Narcotic-induced respiratory depression Methemoglobinemia
Hematologic	Polycythemia Anemia
Source: Kattwinkel J (ed)1 and Behrman RE, Kliegman RM, Jenson HB (eds)4

Remember that not all newborns fit easily into a diagnostic category. A recent prospective study found that fewer than half of symptomatic newborns met textbook criteria for a specific diagnosis.⁶ Some infants were assessed early in the clinical course, and signs and symptoms resolved spontaneously before a disorder declared itself. Other infants had a more prolonged course but still were discharged with a nonspecific diagnosis.

Pulmonary diagnoses

Major pulmonary causes of neonatal respiratory problems include transient tachypnea of the newborn, aspiration, and respiratory distress syndrome.

Transient tachypnea of the newborn. Also known as wet lung, this condition is a retrospective diagnosis of exclusion and the most common cause of neonatal respiratory distress.⁷ Delayed resorption of fetal lung fluid through the pulmonary lymph system causes lung fluid to move into the pulmonary interstitium, leading to reduced pulmonary compliance, increased work of breathing, and compensatory tachypnea.⁸ Plain radiographs of the chest may appear normal or show hyperinflation, a flattened diaphragm, fluid in the fissure lines, and perihilar streaking (Figure 1).⁸ Air bronchograms that suggest pneumonia and reticulonodular patterns typical of respiratory distress syndrome are usually absent.

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Transient tachypnea of the newborn is considered benign and self-limited; recovery occurs within 72 hours. Low levels of supplemental oxygen (fractional inspired oxygen [FiO₂] less than 0.40) are usually sufficient to improve hypoxemia.⁴

Aspiration. Meconium-stained amniotic fluid (MSAF) is present in 12.5% of deliveries,⁹ and the incidence directly correlates with gestational age. The condition causes respiratory depression at one minute after delivery (Apgar score 6 or lower) in 20% to 30% of affected infants.⁹ Of all babies born with MSAF, 4.2% develop meconium aspiration syndrome (MAS),¹⁰ 1.5% require mechanical ventilation,⁴ and 0.2% die.⁹

Traditionally, the pathophysiology of MAS has been simplified into three processes:

• Particulate meconium can function as a ball valve, allowing air to enter the alveoli but not leave. This leads to overinflation, air leak disorders, and ventilation/perfusion (V/Q) mismatches.
• Meconium can counteract surfactant, permitting high surface tension in the alveoli, atelectasis, and further V/Q mismatch.
• Meconium-induced inflammation and cellular damage may cause hypoxic pulmonary vasoconstriction, making the V/Q mismatch worse and exacerbating the hypoxemia¹¹ as well as increasing the risk of infection.

Recent evidence suggests that morbidity from MAS results primarily from in utero distress and asphyxia, not peripartum particulate effect.¹² Tracheal suctioning of nonvigorous newborns is still recommended but has not been proved to reduce the incidence of MAS.^10,13

Aspiration of blood is an underappreciated source of early-onset respiratory distress. Inhalation may occur at delivery, even in the absence of blood-stained amniotic fluid.¹⁴ Aspiration of amniotic fluid also can cause hypoxemia when vernix and epithelial cells block small airways. For any type of aspirate, plain radiographs of the chest may show patchy infiltrates, increased anterior-posterior diameter, hyperinflation, flat diaphragm, and coarse streaking (Figure 2).

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Respiratory distress syndrome, also known as hyaline membrane disease, occurs primarily in preterm infants. The incidence is less than 1% in term infants,¹⁵ whose risk is increased by chorioamnionitis, precipitous delivery, caesarean delivery before 39 weeks, or maternal diabetes.^4,16 The primary cause of respiratory distress syndrome (RDS) is surfactant deficiency,⁴ which results in atelectasis, V/Q mismatch, and hypoxic vasoconstriction. Any process that reduces surfactant can lead to RDS. As with transient tachypnea of the newborn, RDS may mimic bacterial pneumonia initially. After the disorder progresses over the first three or four days of life, diuresis may point towards recovery. Chest films classically show a uniform reticulonodular appearance (ground glass) with air bronchograms, hypoinflation, and atelectasis (Figure 3).

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Cardiovascular diagnoses

Congenital heart disease and persistent pulmonary hypertension of the newborn are the primary cardiovascular causes of neonatal respiratory distress.

Congenital heart disease. Central cyanosis despite adequate ventilation most often results from congenital heart disease. Murmurs may be absent and the electrocardiogram may be normal. In certain congenital disorders, such as coarctation of the aorta, the typical pattern of higher blood pressure in the lower extremities than the upper extremities may be reversed.

If respiratory distress accompanies central cyanosis, a hyperoxia challenge test is recommended to screen for right-to-left shunting, a common finding in many heart defects. The traditional method of performing the test is to obtain room air baseline arterial blood gas (ABG) measurements, which typically show arterial oxygen tension (PaO₂) less than 60 mm Hg. The patient is then given 100% oxygen by oxygen hood for 10 minutes and ABG measurements are repeated. If the PaO₂ remains less than 150 mm Hg, further evaluation with echocardiography is recommended.¹⁷ A PaO₂ greater than 200 mm Hg after the patient has received 100% oxygen is consistent with alveolar hypoventilation and V/Q mismatching, indicating a pulmonary cause.

Simultaneous preductal and postductal pulse oximetry to measure arterial oxygen saturation provides a contemporary alternative to the ABG method of detecting right-to-left shunting. Measurements of SAO₂ from an oximetry sensor on the right hand that are more than 15% higher than readings from a sensor on the foot indicate shunting.¹⁸ As with blood gas measurements, pulse oximetry readings should be taken while the infant is receiving 100% oxygen. The value of pulse oximetry has been confirmed in asymptomatic infants as well as those with symptoms. A recent study found that when SAO₂ was greater than 94% in asymptomatic infants before discharge, its negative predictive value in ruling out congenital heart disease was 100%.¹⁹

Right-to-left shunts sometimes occur with noncardiac disease, however, giving a false-positive result on the hyperoxia challenge test. Examples include hypoglycemia, asphyxia, pneumonia, aspiration, diaphragmatic hernia, pulmonary hypoplasia, persistent pulmonary hypertension, and polycythemia. Even if a noncardiac source is suspected, echocardiography is recommended to exclude cardiac defects.

Persistent pulmonary hypertension of the newborn, or PPHN, arising from abnormally high pulmonary vascular resistance that fails to decline after birth, leads to right-to-left shunting through the patent ductus arteriosus and foramen ovale. Central cyanosis may accompany the newborn's respiratory symptoms. PPHN may be an idiopathic primary disorder or the result of another condition that causes hypoxic vasoconstriction. Because right-to-left shunting is present, the hyperoxia challenge test will be abnormal. A clue to PPHN: The severity of hypoxia is out of proportion to findings on chest films. Echocardiography confirms the diagnosis.

Evaluation and management

Figures 4 and 5 summarize the evaluation and management of term and near-term infants who exhibit tachypnea, grunting, flaring, retractions, or central cyanosis. Respiratory distress requires concurrent investigation and management; correcting cyanosis and assisting ventilation are the initial concerns even in the absence of a definitive diagnosis. Positive pressure ventilation (PPV) at 40 to 60 breaths a minute with 100% oxygen should be started if the newborn's respirations are gasping or absent despite 30 seconds of drying, warming, and stimulation.¹ The oxygen flow rate should be 5 to 10 L/min. Unchecked hypoxia causes pulmonary vasoconstriction and exacerbates hypoxemia. If PPV is required for longer than a few minutes, an endotracheal tube and an orogastric tube for stomach ventilation should be inserted.

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If the infant has central cyanosis but no apparent respiratory distress, give free-flow 100% oxygen. If cyanosis persists beyond one or two minutes, consider PPV. Hyperoxia challenge testing should be performed if PPV does not reverse central cyanosis.

Take a brief history after initial stabilization efforts if this has not already been done. The history should focus on maternal risk factors such as fever, meconium, diabetes, colonization with group B Streptococcus, narcotic analgesia, and a family history of congenital defects. Antenatal ultrasonography findings should be reviewed. Physical examination focused on the oropharynx and nasopharynx, neck, lungs, heart, and abdomen can exclude many of the system-based diagnoses listed in Table 3.

If respiratory difficulties persist after the first several minutes of initial resuscitation, order laboratory tests, which should include a complete blood count to evaluate for sepsis or polycythemia, blood glucose measurement to exclude hypoglycemia, and pulse oximetry or ABG measurements to evaluate for hypoxemia. Central cyanosis in the presence of a normal SAO₂ or PaO₂ increases suspicion of polycythemia or methemoglobinemia. Heel-stick blood from a child with methemoglobinemia may have a chocolate color on a glass slide or filter paper, caused by oxidized ferric iron.

Chest radiographs show heart size and location and help evaluate for diaphragmatic hernia (Figure 6), pulmonary infiltrates, pneumothorax, and other air leak syndromes. Radiographs may not be useful to differentiate pulmonary diseases in the first few hours of life. An electrocardiogram may detect an abnormal axis or ventricular hypertrophy. An echocardiogram should be performed if congenital heart disease is suspected based on a positive family history and findings on a hyperoxia challenge test, ECG, or chest radiographs.

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Nutritional management is based on the newborn's respiratory rate and severity of symptoms. If the rate is less than 60/min and symptoms are minimal, oral feeding is generally safe. If the rate is 60 to 80/min, consider feeding by nasogastric tube. Newborns with a respiratory rate greater than 80/min or moderate symptoms have a high risk of aspiration; withhold feeding. The best choice of intravenous maintenance fluid for the first day of life in term infants is D₁₀W at 80 mL/kg/day.

Giving supplemental oxygen to maintain pulse oximetry values higher than 90% is usually sufficient for less severely ill infants. If the child needs more than 4 to 6 L/min by nasal canula, administration by oxygen hood is helpful. FiO₂ concentrations can vary from 0.21 to 1.0 inside an oxygen hood and should be measured as near the nose as possible. Tank flow rates greater than 7 L/min are required to wash out CO₂ from the oxygen hood.²⁰

When respiratory failure occurs despite initial stabilization, endotracheal intubation and mechanical ventilation can reduce mortality, averting one death for every four patients treated (number needed to treat = 4).²¹ Respiratory failure is defined as persistent apnea or deteriorating blood gases on 100% oxygen (PaCO₂ greater than 60 mm Hg, PaO₂ less than 50 mm Hg, and pH less than 7.25).^8,22

Certain causes of respiratory distress have very specific treatments. Choanal atresia requires use of an oral airway. Robin syndrome is treated by placing the newborn in the prone position and may require insertion of a nasopharyngeal tube to bypass the retropositioned tongue. Pneumothorax is treated by aspiration with a 21- or 23-gauge needle at the fourth intercostal space in the anterior axillary line. Diaphragmatic hernia requires placement of an endotracheal tube and orogastric evacuation of stomach contents.

Medications such as prostaglandin E₁ (Prostin VR Pediatric) or natural bovine pulmonary surfactants such as beractant (Survanta) or calfactant (Infasurf) should be used in consultation with a neonatalogist and in anticipation of transferring the infant to a neonatal intensive care facility. The high rate of significant adverse effects associated with these medications dictates caution.

When to transfer

Based on clinical experience since 1973, the Iowa Perinatal Care Program has derived a "rule of two hours" to guide physicians facing difficult decisions regarding whether to transfer infants in respiratory distress to an NICU. The rule recommends transfer if:

• two hours have passed without improvement
• the chest radiograph is abnormal
• the infant's respiratory condition deteriorates or
• more than 40% oxygen is required to maintain 95% SAO₂.²

To wait or act?

To return to the question posed in the case history at the beginning of this article: Is continued observation or intervention the best choice for baby K. C.? Her uneventful antenatal course and vaginal delivery, respiratory rate of 60/min, and SAO₂ of 95% at 20 minutes of life would seem to make further observation feasible as long as she remains alert, cries in response to stimulation, and maintains good color and tone. Because of the continued grunting, she will need further evaluation with laboratory studies, a chest radiograph, and an ECG. She should also receive oxygen and intravenous antibiotics. Decisions about additional intervention and whether to transfer K. C. to an NICU depend on the findings of the evaluation and her condition over the next few hours.

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21. Henderson-Smart DJ, Wilkinson A, Raynes-Green