Late preterm infants

OVERVIEW: What every practitioner needs to know

Identification of the late preterm neonate

Neonates born between 34 weeks 0/7 days through 36 weeks 6/7 days are defined as “late preterm” neonates.

This definition was selected so that greater attention to the special needs of this group would be identified, resulting in more diligent evaluation, monitoring, and follow-up by health care providers.

This definition of late preterm also conveys an impression that this group of neonates is still premature, not almost term, as the "near term" definition may imply.

What diseases/conditions are prevalent in the late preterm infant?

Recent research that focused on late preterm births has revealed that this group of patients experiences a higher incidence of preterm neonatal complications, such as respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, temperature instability, jaundice, and feeding difficulties and are at a higher risk of having long-term neurologic developmental concerns when compared with their term counterparts.

Late premature neonates have also been found to require additional resources, leading to higher hospital costs secondary to longer lengths of hospital stay and higher rates of admission to the neonatal intensive care unit (NICU). Furthermore, late preterm infants are more likely to be rehospitalized after initial hospital discharge.

What early respiratory neonatal morbidities consitute risk for late preterm infants?

Late preterm neonates were 8 times more likely to be diagnosed with respiratory distress syndrome, 9 times more likely to be placed on nasal continuous positive airway pressure, 5 times more likely to be placed on a ventilator, and 42 times more likely to require surfactant supplementation when compared with the term neonates who were admitted to the NICU.

Respiratory morbidities in late premature neonates delivered spontaneously or by elective cesarean section have been well documented and are responsible for a significant number of admissions to the NICU each year.

Late preterm neonates have a higher incidence of transient tachypnea of the newborn, respiratory distress syndrome, pulmonary hypertension, and respiratory failure than do term infants, each of which contributes to higher rates of NICU admissions. When admitted to the NICU, these late preterm babies require oxygen therapy and ventilatory support, including mechanical ventilation.

Apnea occurs more frequently in late preterm neonates and has an incidence of 4%-7% compared with less than 1%-2% in term infants.

Pathophysiology of Respiratory Morbidities

Late preterm neonates have an immature lung structure associated with delayed intrapulmonary fluid absorption, surfactant deficiency, and inefficient gas exchange, which is responsible for the increased incidence of respiratory morbidities seen in this cohort compared with term infants.

There is considerable evidence that physiologic events in the last few weeks of pregnancy, coupled with the onset of spontaneous labor and hormonal changes, affects the fetus and the mother in ways that result in the rapid maturation and preparation of the fetus for delivery and a smooth neonatal transition.

Spontaneous delivery during term gestation is accompanied by a surge in endogenous steroids and catecholamine secretion, which is responsible for some of the pulmonary maturational effects.

When delivery occurs when the fetus is of late premature gestational age, especially when cesarean section is carried out before the onset of labor, the fetus is deprived of these hormonal changes, making the neonatal transition more difficult and increasing the risk of acute respiratory issues in the early neonatal period.

Several underlying factors such as increased susceptibility to hypoxic respiratory depression, decreased central chemosensitivity to carbon dioxide, increased sensitivity to laryngeal stimulation, and decreased upper airway muscle tone, predispose these neonates to apneic episodes.

Why are late preterm infants at risk for gastrointestinal neonatal morbidities?

The late preterm infant may have difficulty in coordinating suck and swallowing, with a resultant delay in successful breast feeding and poor weight gain and dehydration during the early postnatal period, potentially increasing the likelihood of rehospitalization or delaying discharge. Additionally, mothers who deliver near but not at term are more likely to deliver more than one infant; have medical conditions such as diabetes, eclampsia, or chorioamnionitis; or deliver by cesarean section delivery, which may also affect breast-feeding success.

Taken together, the maternal and infant problems place the late preterm breast-feeding neonate at increased risk for hypothermia, hypoglycemia, excessive weight loss, slow weight gain, failure to thrive, prolonged artificial milk supplementation, exaggerated jaundice, dehydration, breast-feeding failure, and rehospitilization.

Pathophysiology of Gastrointestinal Morbidities

Deglutition, peristaltic functions, and sphincter control in the esophagus, stomach, and intestines are less mature in late preterm infants compared with term infants, making them more vulnerable to poor feeding, reflux, and feeding intolerance.

Because of their immaturity, late preterm neonates may be more sleepy, have less stamina, and have more difficulty with latching on to the mother's breast.

Why are late preterm infants at risk for bilirubin-induced encephalopathy?

The mechanisms that potentially could account for the increased susceptibility to bilirubin-induced central nervous system injury in late preterm neonates have not been well defined. However, some of the factors that can potentially account for this are the diminished serum bilirubin binding capacity due to the lower serum albumin levels in the late preterm group, an enhanced permeability of the blood-brain barrier to unconjugated bilirubin influx, and an immaturity of neuronal protective mechanisms.

Hyperbilirubnemia in late preterm neonates is often more prevalent, and when it does occur it is usually more severe and its course is more protracted than in term neonates. Compared with term neonates, late preterm neonates were at increased risk for the development of kernicterus in the pilot USA Kernicterus Registry. They are also at risk for the development of signs of bilirubin neurotoxicity at an earlier postnatal age.

Jaundice in the late preterm infant results from an increased bilirubin load from increased bilirubin production and decreased bilirubin elimination. Moreover, late preterm neonates demonstrate slower postnatal maturation of hepatic bilirubin uptake and bilirubin conjugation compared with their term counterparts.

This exaggerated hepatic immaturity contributes to the greater prevalence, severity, and duration of neonatal jaundice in late preterm infants.

The immaturity of the suck-swallow mechanism discussed previously can also place late preterm neonates who are breast fed at risk for severe neonatal hyperbilirubnemia. Inadequate breast milk intake, in addition to contributing to varying degrees of dehydration, can enhance hyperbilirubnemia by increasing the enterohepatic circulation of bilirubin and the resultant hepatic bilirubin load.

In the context of the exaggerated hepatic immaturity of the late preterm neonate, any further increase in the hepatic bilirubin load results in more marked hyperbilirubnemia.

Why are late preterm infants at risk for hypoglycemia?

Late preterm infants are more likely to encounter stressful conditions (e.g., birth asphyxia, septicemia, cold stress, and respiratory distress) that require mobilization of hepatic glycogen stores to maintain satisfactory blood glucose concentrations.

Hepatic glycogen stores increase as gestation progresses. Thus, glycogen stores in late preterm infants are more easily depleted than in term infants.

Relative to term infants, gluconeogensis may be compromised in preterm infants.

Why are late preterm Infants at risk for cold stress?

Cold stress should be of greater concern in both the very preterm infant and the larger late preterm cohort alike and is an important stressor that can potentially hinder a successful transition to the extrauterine environment or precipitate persistence of the fetal circulation, pulmonary hypertension, respiratory distress syndrome, and other neonatal respiratory morbidities.

Late preterm infants are particularly vulnerable to cold stress because of their immature epidermal barrier, a higher ratio of surface area to birth weight than term infants have, and the need for more frequent delivery room interventions.

Late preterm neonates also have less white adipose tissue for insulation and cannot efficiently generate heat from brown adipose tissue as effectively as can term infants, putting them at risk for hypothermia.

Other factors that can promote heat loss are large temperature gradients between the infant and the ambient temperature of the delivery room, large evaporative heat loss from the wet surface of the newborn, and conductive heat losses to the cooler surfaces on which the infant is placed.

Why are late preterm infants at risk for infections during neonatal morbidities?

Compared with term and extremely preterm infants, late preterm neonates are intermediate with regard to immunologic maturity. Although the overall mortality rate from infection is low for late preterm infants, an immature immune system could potentially increase the risk of neonatal complications, prolong hospital stay and increase health care costs.

Late preterm neonates have an increased risk for immaturity of a range of developmental processes, resulting in respiratory distress, temperature instability, jaundice, and hypoglycemia. Since many of these clinical findings are some of the common initiating signs of neonatal sepsis, there is an increased likelihood of evaluations for sepsis and antibiotic therapy in late preterm neonates when compared with their term counterparts.

In evaluating the pathophysiology of infection risk for the late preterm infant, little specific data on the host-defense capability of the late preterm term exists. It is widely known that the host has two major systems of defense, the nonspecific innate immune mechanism and the adaptive immune system. Innate immunity includes host defense mechanisms that operate effectively without previous exposure to an antigen.

These mechanisms include physical barriers such as the skin and mucous membrane, which when breached triggers the release of mast cells and tissue macrophages. These mast cells can then activate T lymphocytes initiating a specific immune response that is often an important component of both innate and acquired immunity. Whether there are subtle changes in mast cell numbers or an optimal mast cell response to an antigen in the near term neonate is unclear.

Why does the late preterm infant have developmental delays?

The late preterm neonate is more likely to have developmental delay within the first 3 years of life and are more likely to be referred for special needs preschool resources. Furthermore, they are more likely to have problems with school readiness. Given the increased numbers of late preterm infants, these findings underscore the potential economic and social risks posed by the late preterm infant and the concomitant need for additional educational and social services for this growing population.

Late preterm neonates have less mature neural control of respiration and immature brain development when compared with their term counterparts. Furthermore, there is a critical period of brain growth and development that occurs in late gestation that is vital to the development of various neural structures and pathways. In fact, approximately 50% of the increase in cortical volume occurs between 34 and 40 weeks of gestation. During this critical period in the growth and development of the human brain any type of neural insult can lead to profound consequences for later brain development.

The late preterm brain at 34 weeks of gestation weighs only 65% of the term brain, with a 35% increase in growth still needed to reach the term brain weight. In early gestation, unmyelinated white matter is the predominant neural tissue, which progressively changes to myelinated white matter by late preterm. Gray matter volume increases throughout gestation and specifically has a rapid increase between 36 and 40 weeks of gestation because of neural differentiation and gyral formation.

Therefore, in the late preterm infant, the period between 34 and 40 weeks of gestation is critical, since the relative percentage of both gray matter and myelinated white matter to total brain volume increases exponentially. Recognizing that the brain reaches only 65% of term weight by 34 weeks underscores the immaturity of the late preterm brain and its potential vulnerability to multiple insults that interfere with basic mechanisms of neuronal and glial maturation during this time frame.

These findings underscore the potential economic and social risks posed by the late preterm infant and the concomitant need for additional educational and social services for this growing population.

What clinical parameters should the physician use to help confirm the diagnosis of a late preterm infant?

Late preterm neonates should be identified as a high-risk group in need of delivery room attendance for potential resuscitation support because of the above-mentioned risks of immaturity of the physiologic systems and in response to stress factors during labor and birth.

The last weeks of pregnancy are critical for complete fetal development and maturation. Biochemical and hormonal modifications associated with spontaneous birth are key factors required for an adequate transition to extrauterine life. Interruption of pregnancy before the occurrence of these maturational events can hinder the respiratory and hemodynamic transition that normally should take place soon after birth.

Researchers have found that except for tracheal aspiration for meconium, the chance of needing any resuscitation procedure was approximately two times higher in the late preterm group compared with the full-term group.

Pediatricians need to be alert to the potential problems of suboptimal breast-feeding in late preterm neonates and not be misled by the seemingly satisfactory breast-feeding efforts of these late preterm neonates during their initial stay in the hospital. During this first observed period, limited colostrum volume make it a challenge to adequately assess the effectiveness of breast-feeding.

Ultimately, the best clinical strategy to avoid the development of marked hyperbilirubnemia and the associated risk of bilirubin encephalopathy in the late preterm neonate is preventive. It includes nursing and parental education, screening for jaundice in the newborn nursery, the provision of lactation support, timely postdischarge follow-up, and appropriate treatment when clinically indicated.

Recognition of cold stress after birth, especially in late preterm neonates, and rapid intervention in the form of prevention strategies is key. Strategies that can help to accomplish a smooth transition include thorough drying of the skin and scalp with warm blankets, proper skin-to-skin contact with the mother, and swaddling with warm blankets.

It is important for providers taking care of this cohort of neonates to pay close attention to the anticipation, recognition, diagnosis, and therapy of neonatal hypoglycemia. Cold stress and hypoglycemia represent components of adaptation that are rarely completed within the delivery room but rather extend through the first day of life. Irrespective of the mode and place of care—whether in the newborn nursery, rooming with the mother, or in the intensive care unit, repetitive body temperature and serum glucose measurements are necessary for proper management.

Confirming the diagnosis

A Clinical Decision Algorithm for Monitoring the Late Preterm Neonate

Late preterm neonates need closer monitoring in a transitional nursery or NICU than do term infants.

Feeding: Early initiation of feedings with increased frequency. Trained nursing staff should observe for suck-swallow coordination and reduced endurance and have a lactation consultation with the mother within 24 hours of birth.

Hyperbilirubnemia: Serum testing of bilirubin at 24 hours, visual assessment for jaundice in hospital every 8-12 hours, education by the providers instructing parents to look for worsening jaundice such as visible yellowing of the skin, inadequate feeding, decreased activity with decreased urine output, and follow-up with a pediatrician within 4-5 days are necessary.

Thermoregulation: Axillary temperature should be taken immediately after admission and every 4 hours during the hospital stay. The infant should demonstrate stable temperature for at least 48 hours in an open crib before discharge.

Close monitoring by the nursing staff for signs and symptoms of respiratory distress in the first 48 hours is important. Parents should be trained to look for signs of respiratory distress, such as nasal flaring, increased retractions, and grunting.

What are the possible outcomes of the condition?

Late preterm infants have a higher incidence of transient tachypnea of the newborn, respiratory distress syndrome, pulmonary hypertension and respiratory failure when compared with term infants.

The chance of needing any resuscitation at birth in late preterm infants is almost twice that in term infants.

Late preterm neonates are two to four times likely to have severe jaundice when compared with term infants.

Late preterm neonatesare more susceptible to cold stress, more often requiring phototherapyfor jaundice, and are more likely to have problems with feeding.

Late preterm neonates are at higher risk than term infants to have developmental delay and school readiness issues.

What causes this disease and how frequent is it?

Late preterm newborns are the fastest growing subset of babies. The factors that have contributed most significantly to the recent increased incidence of late premature births include the increasing proportion of women choosing to have babies later in life, increased demand for assisted reproductive technology, increased incidence of multiple gestation pregnancies, and the increased rates of childbirth interventions such as cesarean section and induction of labor.

In the year 2006, approximately 1/8 newborns in the United States were born prematurely, representing 542,893 US births and12.8% of all live births. However, 75% of these early births, or about 9% of total US births in 2006, were late preterm infants, born between 34 and 37 weeks of gestation.

How can late preterm births be prevented?

Every effort should be made to install hospital guidelines to ensure that elective cesarean delivery or induction of labor be avoided before 40 weeks of gestation.

At all gestational ages, the risk of continuing the pregnancy must be carefully balanced against the risk of delivery and associated risks of prematurity.

Ongoing controversies regarding etiology, diagnosis, treatment

Parents and physicians should be aware that infants who are delivered at late preterm gestational age have substantially higher risks for early neonatal morbidities. Because of the high rates of morbidity, especially respiratory issues, further discussion must take place as to where the most appropriate level of care can be provided to these infants. This should lead to consensus and an improvement in the overall care for this group of neonates.

It is important to establish multidisciplinary guidelines for the care of late preterm infants at the local, regional, and national level with specific goals to address

In-hospital assessment and care of late preterm infants

Discharge planning and process

Short- and long-term follow-up of these neonates

A comprehensive understanding of these issues related to late preterm infants by the physicians, nurses, hospital administrators, and parents is essential to determine the resources to care for a cohort of infants in whom the risk of medical problems is often overlooked.

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