Although often considered healthy, especially in comparison to their extremely premature counterparts, a growing body of evidence shows these infants are at substantial risk of neonatal and long-term morbidities, as well as mortality.
The decision to proceed with delivery, whether medically indicated or secondary to preterm labor/premature rupture of membranes (PROM), requires balancing the consequences of continued pregnancy to both the mother and the baby.
Some, but not all of late preterm (LPT) infants will require intensive care, while others may be cared for safely in the term nursery. Available term nursery resources, including expertise with LPT infants and nursing availability, may dictate where the well-appearing LPT infant should be admitted.
Definition
Infants born LPT are between 34 and 0/7 weeks’ to 36 and 6/7 weeks’ gestation.
LPT infants are more likely to require assistance at delivery and their deliveries should be attended by at least one person with expertise in newborn care and resuscitation.
Risk factors should be evaluated and assessment performed at delivery to allow proper admission of the infant to either the neonatal intensive care unit or the normal newborn nursery.
Incidence
Premature infants account for more than 10% of deliveries; LPT infants constitute the largest portion of prematurely delivered infants accounting for over 71% of all preterm births.
LPT infants frequently require intensive care unit (NICU) admission. Overall rates of NICU admission for LPT infants vary from 35% to 75% by center, with a smaller component of transfer from term nursery. Rates of NICU admission are inversely correlated with gestational age: 34 weeks: 43% to 100%, 35 weeks: 22.5% to 43%, 36 weeks: 12.3% to 40.5%.
Many centers routinely admit all babies less than 35 weeks to a special care unit.
Growing national and international awareness of the consequences of LPT birth has finally led to a decrease in birth rates: following a steady increase in the number of infants born LPT since 1981, this number has now decreased each year since 2006. However, more than 339,000 LPT infants born in the United States in 2010 still create a substantial economic and health care burden.
Pathophysiology
LPT infants are at risk for illness at birth due to both their immaturity and a high incidence of complicated pregnancies in this group.
LPT infants are often the product of a medically complicated pregnancy and delivered by cesarean section, which further increases the risk to the neonate.
Immaturity causes delayed clearance of lung fluid, risk of respiratory distress syndrome, and increased risk of apnea.
LPT infants are also at increased risk for hypothermia, hypoglycemia, and feeding difficulties due to their small size and immature feeding skills.
There is also a higher risk on neonatal sepsis in pregnancies complicated by PROM and chorioamnionitis.
Risk factors
Birth at each week earlier in gestation is a strong risk factor for NICU admission.
Maternal illness, including diabetes and preeclampsia, also increases the risk for an LPT delivery and NICU admission.
Cesarean delivery in the absence of labor also increases the risk of respiratory distress and requirement for NICU care.
Other pregnancy complications, including placental abruption, bleeding, and PROM increase the risk for hypoxic events and infection, and thus both NICU admission and death.
Intrauterine growth restriction and infants born small for gestational age (SGA, <10% tile) are also more likely to require NICU admission and have a higher risk of mortality.
Clinical presentation
Signs and symptoms
To avoid NICU admission, the LPT infant must be well appearing in all areas.
Any cardiorespiratory instability should be an indication for NICU admission including hypoxia, tachypnea (respiratory rate >60), increased work of breathing, apnea, or heart rate instability.
Hypothermia and hypoglycemia that are unresponsive to simple interventions should also require ICU care (see below).
The infant must also demonstrate readiness to feed and an interest is feeding.
Clinical variability
There is a wide variety of clinical presentations based on gestational age, gender, pregnancy, and delivery factors. Each infant must be assessed individually.
Diagnosis
Prenatal care allows for dating and best estimate of gestational age, but evaluation of maturity should also be done at delivery. All suspected LPT infants should have a New Ballard Score Maturational Assessment of Gestational Age performed in order to accurately assess the level of maturity (Figure 28-1).
Patients may be younger or older than expected.
Evaluation should also be done for physiologic factors that require ICU care.
Management
As shown in Figure 28-2, the composite incidence of respiratory distress, infection, hypoglycemia, feeding difficulties, and other neonatal morbidities is seven times higher in LPT infants compared to those born at term. Risk factors should be evaluated and a clinical assessment at delivery performed including assessment of gestational age, weight, respiratory distress, systemic illness, and readiness to feed to allow proper admission of the infant to either to neonatal intensive care unit or the normal nursery. Whether admitted to the NICU or term nursery, LPT infants need close observation. Because of the high risk of morbidities and NICU admission, some units choose to admit all infants born prior to 35 weeks’ gestation.
Respiratory distress syndrome
Respiratory distress syndrome (RDS) is the pattern of hypoxia, poor gas exchange, and respiratory failure due to lung immaturity and insufficient production of pulmonary surfactant.
RDS is significantly more common in LPT infants than those born at term, occurring in 4% to 5% versus <0.1%. It is the most common cause of respiratory distress in LPT infants and the most common reason for NICU admission.
Incidence varies by gestational age and is highest at 34 weeks (10.6%), decreasing at 35 (6.0%) and 36 weeks (2.7%). Incidence is also higher in early term (37 and 0/7 to 38 and 6/7) infants. Mechanical ventilation is required in 2% to 3% of LPT infants; this is primarily for RDS.
Pulmonary surfactant is composed of phospholipids and proteins produced by type II alveolar cells in the distal lungs and acts to reduce surface tension in the alveoli. This improves pulmonary compliance and decreases the pressure necessary to keep the alveoli open, preventing atelectasis. Surfactant production increases with advancing gestational age with a surge at 35 weeks, but full production is not present until term.
Prematurity is the most important risk factor, but absence of spontaneous labor and delivery by cesarean section also increase risk.
RDS is characterized by tachypnea with evidence of increased work of breathing (nasal flaring, retractions, grunting), and hypoxia.
Respiratory examination often reveals poor air entry.
Blood gas analysis may reveal hypoxia (PaO2 <80) and hypercarbia (PaCO2 >50).
Typical chest x-ray (CXR) findings include opacification (“ground-glass” appearance), air bronchograms, and atelectasis; the heart borders may be obscured.
There is large variability in clinical appearance with some infants having mild disease and other in fulminant respiratory failure; this does not always correlate with CXR appearance. There is often overlap with other neonatal causes of respiratory distress, including transient tachypnea of the newborn and pneumonia.
RDS is a clinical diagnosis, made in infants that fit the clinical picture as described above and respond to therapies, including exogenous surfactant.
Management includes
Respiratory support should be given as needed to treat hypoxia, hypercarbia, and work of breathing. Oxygen administration alone is often insufficient and can be detrimental: Affected infants usually require positive end expiratory pressure (PEEP) in the form of continuous positive airway pressure (CPAP) or intubation.
Intubated infants should receive surfactant.
Further details of respiratory care are described in Chapter 7.
Prenatal administration of betamethasone, which decreases the risk of RDS in more preterm infants, has not been shown to be helpful in LPTs.
Prognosis
Infants that require only CPAP or respond well to a single dose of surfactant often recover and have a low incidence of permanent sequelae. Infants intubated more than 6 hours are more likely to have prolonged courses and have a higher risk of mortality.
Despite their relatively large size, LPT infants can have severe RDS, resulting in prolonged hospital stays, pulmonary hypertension, need for extracorporeal membrane oxygenation (ECMO), and even death.
Chronic lung disease, or bronchopulmonary dysplasia, is diagnosed in ∼3% of LPT infants.
Mortality from severe RDS is around 1%; this is responsible for a significant component of the mortality in LPT infants. However the large majority of infants recover well, without permanent sequelae.
Transient tachypnea of the newborn
Transient tachypnea of the newborn (TTN) is characterized by significant tachypnea with mild increase in work of breathing that results from delayed resorption of fetal lung fluid.
TTN is generally considered the second most common cause of respiratory distress in the LPT infant, occurring in 3% to 4% of the population, though in some studies it is more common than RDS.
Once again, incidence is increased at lower gestational ages: The Consortium on Safe Labor found the incidence of TTN was highest at 34 weeks (64/1000 births) and 35 weeks (46/1000 births) and decreased with advancing gestational age until 39 weeks.
The primary mechanism causing TTN is delayed resorption of fetal lung fluid, a complex process that is now understood to begin several days before spontaneous delivery. Hormonal changes that accompany labor and the addition of exposure to oxygen and mechanical stretch at delivery cause the lung epithelium to become a highly effective absorptive surface. The sodium selective epithelial channel, ENaC, plays an essential role via active sodium transport. ENaC production is developmentally regulated with lower levels in preterm infants, especially those with evidence of respiratory distress and TTN.
In addition to prematurity, maternal and infant factors can increase the risks of TTN.
Maternal diabetes.
Maternal asthma.
Cesarean delivery, especially in the absence of labor. This effect is exaggerated in preterm infants.
Macrosomia.
Polyhydramnios.
Male gender.
Infants present with marked tachypnea beginning in the first 4 hours of life (80 to 140 breaths/min), mild cyanosis, mild work of breathing, no evidence of infection, classic CXR findings (see below), and resolution by 2 to 5 days.
There is wide variability with many infants having mild tachypnea that requires only observation and others with more significant tachypnea necessitating nutritional support and supplementary oxygen. A very small portion of neonates with TTN will have fulminant respiratory failure that requires mechanical ventilation and substantial support.
History, clinical appearance, and CXR findings are used in the diagnosis of TTN. Characteristic CXR findings consistent with TTN include hyperinflation with flattened diaphragms, signs of vascular congestion including increased perihilar markings, fluid in the interlobar fissures, and mild streaky opacity that is uniform across lung fields. There is no specific testing that confirms the diagnosis of TTN.
The mainstay of treatment for TTN is supportive care, as there are no specific targeted therapies that are standard of care. Infants whose primary symptom is tachypnea, without hypoxia or signs of increased work of breathing such as grunting or retractions, may be observed until symptom resolution without specific respiratory treatment.
Tachypnea that is accompanied by additional signs of respiratory distress, hypoxia, persists longer than 6 hours, or is accompanied by other systemic symptoms merits an evaluation and presumptive treatment for sepsis as well as the appropriate respiratory support. Supplemental oxygen should be provided to keep saturations >95% with additional support as needed.
The prognosis for TTN is generally excellent, with full recovery expected in two-thirds to three-quarters of infants by 72 hours. Rapid resolution of symptoms is seen in majority of the infants. However, secondary complications including prolonged tachypnea, respiratory failure, pulmonary hypertension, acidosis, and air leak syndrome can occur; this is estimated in less than 10% of infants with TTN. Long-term morbidities and mortality are rare and mostly occur in infants with severe illness and secondary complications.
Hypoglycemia
Generally defined as a blood sugar <40 mg/dL in the first 4 hours and <47 mg/dL thereafter is considered hypoglycemia. However, here is no firm consensus definition as healthy infants may have blood sugars <40 mg/dL in the early hours of life that resolve spontaneously. Symptomatic or persistent hypoglycemia that does not respond to feeding is of much larger concern.
The incidence is estimated at 6% to 15% in LPT infants and varies with gestational age, size, risk factors, and definition of hypoglycemia, but may be even higher if close screening is done.
At birth the infant is separated from a constant energy supply and must transition to enable glucose homeostasis.
LPT infants have immature liver mechanisms for gluconeogenesis and decreased energy stores.
Infants born to diabetic mothers (IDM) frequently have better stores but may have excessive insulin production resulting in hypoglycemia.
Poor oral feeding skills are common in LPT infants and contribute to the problem.
Large for gestational age (LGA) and SGA infants are at increased risk for hypoglycemia. IDM infants are at high risk and may have prolonged hypoglycemia. Respiratory distress and systemic illness both increase the risk for delayed feeding and hypoglycemia.
Infants may initially present with fussiness, irritability, jitteriness or tremors, and poor feeding. More severe symptoms include lethargy, seizures, poor tone, abnormal cry, and eventually apnea and coma.
There is a substantial variability in level, which results in symptoms, with some infants asymptomatic even at glucose <30 mg/dL.
Bedside glucose test strips may be used for screening, but are unreliable at low and high glucose levels. STAT serum glucose level should be evaluated in the laboratory for symptomatic infants or those with low screens.
Medical management of LPT infants and those with risk factors should be screened routinely for hypoglycemia.
Three normal levels prior to feeds are sufficient in well infants with adequate oral intake, though those with risk factors require more prolonged screening (48 to 72 hours).
Asymptomatic infants can be initially fed by mouth or gavage fed, though intravenous (IV) glucose may be required.
Symptomatic infants should be treated with IV dextrose immediately with the level rechecked after treatment.
Treatment is discussed in more detail in Chapter 20. The Committee on Fetus and Newborn has published general guidelines for management.
Hypoglycemia that is easily treatable with oral, orogastric feeds or small amounts of IV dextrose usually resolves quickly without permanent sequelae. Brief, transient, and asymptomatic hypoglycemia has a good prognosis, regardless of glucose level. Infants of diabetic mothers often have longer courses and require IV glucose but will eventually self-resolve. Prolonged, repeated, and significant (<40 mg/dL) hypoglycemia requires more of a workup and is associated with neuronal cell death with serious neurodevelopmental sequelae.
Thermoregulation and hypothermia
Normothermia is conventionally defined as a temperature from 36.5°C to 37.4°C. Lower temperatures, especially under 36.0°F, can lead to cold stress and compromise infant well-being.
Up to 30% of infants in term nursery may have a temperature <36.5°C. Incidence of lower temperatures (<36.0°C) is up to 40% in LPT infants treated in term nurseries. Risk of hypothermia in the NICU, where infants are often in servoregulated beds, is lower, around 2%.
Delivery removes the maternal heat source and requires the neonate to make a rapid adjustment to maintain his own temperature. The largest part of heat losses are evaporative and radiation losses to the external world. Heat is normally generated through oxidation of brown adipose tissue. Preterm infants are deficient in adipose tissue and have thin, unkeratinized skin, leading to decreased heat production and increased loss.
Lower gestational age and size, low birthweight (<2500 g), and SGA infants are at increased risk. Maternal diabetes is protective.
Hypothermia/cold stress can present with shivering, increased respiratory distress, poor perfusion, hypoglycemia, metabolic acidosis, and apnea. It can be difficult to differentiate from sepsis.
Depending on size and degree of prematurity, some LPT infants will have adequate thermoregulation.
Central temperature should be taken for accurate diagnosis, usually via the axilla or rectally. LPT infants should be monitored rather than waiting for the onset of symptoms.
For managing the LPT infant at risk for hypothermia, temperature should be monitored every 3 to 4 hours until the infant has demonstrated good thermoregulation while lightly dressed with one thin blanket.
Infants being cared for in the term nursery should also be monitored for at least 24 hours.
Persistent hypothermia may require NICU admission and evaluation for sepsis.
Effective drying at delivery and avoiding early baths (<4 hours) may help prevent hypothermia.
Small infants (<2000 g) may require an isolette to maintain temperature and avoid radiant loss.
Though easily treatable, hypothermia can worsen respiratory illness or hypoglycemia and require additional care. Hypothermia is associated with increased mortality in extremely premature infants but this association has not been shown for LPTs.
Sepsis/pneumonia
Bacterial or viral infection can occur in the neonate prior to, during, or after delivery. LPT infants are at increased risk of infection both in the peripartum and early neonatal period.
The nonspecific nature of the symptoms of sepsis means a larger portion of LPT infants are treated with antibiotics (14.6% to 37.1%), though less than 2% will have culture proven sepsis. Suspected or diagnosed infection is also a common reason for readmission of the LPT infant.
Perinatal infection and chorioamnionitis are implicated in preterm birth and may be the reason an infant is delivered prematurely. In addition, an immature immune system and decreased transfer of maternal antibodies in the LPT infant increase the risks of infection and disease severity in the first several weeks of life.
Known risk factors for infection include maternal fever, chorioamnionitis, malodorous amniotic fluid, prolonged rupture of membranes, and fetal tachycardia. However, a large number of infants diagnosed with sepsis have no documented risk factors.
Signs of infection include temperature instability, hypoglycemia, poor feeding, tachypnea, and apnea in the early stages, and may not be distinguishable from consequences of prematurity itself. Specific symptoms of infection are rare, which necessitates a low threshold for evaluation and treatment.
There is wide variability in symptomatology with some infants having mild symptoms and others presenting severely ill with cardiovascular and respiratory collapse.
Infants with the above signs and symptoms should have evaluation for sepsis with a blood culture and CBC. Inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are nonspecific but trending values can be useful in infants with a prolonged course. Additional evaluation, including lumbar puncture, is done on a case-by-case basis.
Supportive care and antibiotic therapy are mainstays of treatment. Ampicillin, which covers group B Streptococcus and Listeria, is usually appropriate in combination with a gram-negative agent, such as gentamycin. Local resistance patterns and any antibiotic treatment of the mother during pregnancy should be taken into account.
Early treatment of suspected sepsis is key as there is significant morbidity and mortality if the neonate is severely ill when treatment begins. Infants that are diagnosed quickly without significant systemic illness do well and often have a quick recovery. Long-term sequelae are dependent on degree of illness and compounding factors, such as meningitis. Full recovery is expected in infants with minimal symptoms. Infants presenting in shock with respiratory and cardiovascular failure or coagulopathy have substantial morbidity and mortality.
Early developmental/therapeutic interventions
Feeding therapy
Use of a speech or occupational therapist skilled at infant feeding may be helpful; however, slow oral feeding is likely just a sign of immaturity in the LPT infant and will resolve with or without therapy.
A lactation specialist is useful to support the mother and her breast-feeding infant.
Physical therapy
An LPT infant with a prolonged NICU stay may benefit from a PT consult to evaluate positioning, state regulation, and early gross motor skills, as well as parent education on the expected patterns of development in preterm infants.
Prognosis
Early predictors
Older, larger infants are more like to remain in term nursery and can be discharged after 48 hours with close follow-up.
Average length of stay (LOS) is approximately 6 days, two to three times that for term infants.
Infants with multiple morbidities will require more prolo-nged care.
Outcomes
Rates of serious long-term morbidities and mortality are low but significantly higher than for term infants.
Neonatal mortality rates increase with each week earlier in gestation (36 weeks 2.8/1000, 35 weeks 4.8/1000, and 34 weeks 7.1/1000).
Infants with congenital anomalies are often delivered in the LPT period and have worse outcomes.
Singleton LPT infants delivered after spontaneous labor and an uncomplicated pregnancy are at lowest risk and have mortality rates approaching those of term infants (<0.5/1000 live births).
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