Pediatrics

Late preterm infants

OVERVIEW: What every practitioner needs to know

Are you sure your patient is late preterm?

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

The 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. The definition also conveys the reality that this group of neonates is still premature, not almost term, as "near term" implies.

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

Late preterm infants are subject to a higher incidence of respiratory distress syndrome, transient tachypnea of the newborn, hypoglycemia, temperature instability, jaundice and feeding difficulties, and are at a higher risk of long-term neurologic disabilities as compared with full-term infants.

Late premature neonates thus require additional healthcare resources. They may require longer hospital stays and admission to neonatal intensive care units (NICUs). They are also more likely to be re-hospitalized and to require neurodevelopmental and education support during childhood.

Respiratory morbidities:

Late preterm neonates are 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 term neonates along with a higher incidence of transient tachypnea of the newborn and primary pulmonary hypertension. As a result, the incidence of NICU admission is high.

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

Pathophysiology

Late preterm neonates may have immature lungs associated with delayed intrapulmonary fluid absorption, surfactant deficiency and inefficient gas exchange. Infants born prior to 39 weeks are deprived of events in the last few weeks of pregnancy that promote lung maturation and preparation of the fetus for a smooth perinatal transition. This is particularly true if pregnancy is terminated electively, prior to spontaneous onset of labor.

Increased susceptibility to apnea is a result of increased susceptibility to hypoxic respiratory depression, decreased chemosensitivity to carbon dioxide, increased sensitivity to laryngeal stimulation and decreased upper airway muscle tone.

Gastrointestinal morbidities:

Late preterm infants may have difficulty in coordinating breathing, suck and swallowing, with delay in successful breast feeding, poor weight gain and even dehydration, increasing the likelihood of delayed discharge or rehospitalization. Successful breast feeding may also be impaired by medical complications associated with late preterm delivery such as multiple gestation, cesarean delivery, chorioamnionitis, maternal diabetes and preeclampsia. Poor feeding increases the risk of hypoglycemia, dehydration, slow weight gain, need for formula supplementation and exaggerated jaundice. Such complications prolong initial hospitalization and increase the need for rehospitalization.

Pathophysiology

Deglutition, intestinal peristalsis and sphincter control in the esophagus and stomach predispose late preterm infants to poor feeding, reflux and feeding intolerance.

Late preterm neonates may be sleepier, have less stamina and have more difficulty with latching on to the mother's breast.

Hyperbilirubinemia:

Hyperbilirubinemia in late preterm neonates is more common and may be severe and prolonged. Late preterm neonates are at increased risk for kernicterus and lesser signs of bilirubin neurotoxicity. Contributing factor may be decreased serum bilirubin binding capacity due to the lower serum albumin concentrations, enhanced permeability of the blood-brain barrier and immaturity of neuronal protective mechanisms.

Pathophysiology

Jaundice in the late preterm infant is problematic. Increased enterohepatic circulation of bilirubin is due to poor feeding and decreased gastrointestinal motility. Bilirubin elimination is decreased because of slower maturation of hepatic bilirubin uptake and conjugation.

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.

Pathophysiology

Hepatic glycogen stores increase as gestation progresses. Thus, glycogen stores in late preterm infants are small and easily depleted. Furthermore, gluconeogenesis may be compromised.

Hypothermia:

Late preterm infants are vulnerable to cold stress because of immature skin, a high ratio of surface area to birth weight (increasing the ratio of loss to generation of heat) and the need for delivery room interventions. Other factors are large temperature gradients between the infant and the temperature of the delivery room, evaporative heat loss from wet skin and conductive losses to cool surfaces. Late preterm infants have less brown adipose tissue to generate heat and less white adipose tissue for insulation.

Infection:

Late preterm neonates are relatively immature immunologically. Although the overall mortality from infection is low, it is higher than for full term infants. Moreover, signs and symptoms related to immaturity such as respiratory distress, temperature instability, jaundice and hypoglycemia are also common in neonatal sepsis. Thus, preterm infants are likely to be evaluated for sepsis and receive unnecessary antibiotic therapy.

What clinical findings should the physician use to help confirm the diagnosis of a late preterm infant and what treatment should be initiated?

Late preterm neonates should be identified as a high-risk group in need of delivery room attendance for potential resuscitation because of immature physiology and susceptibility to stress during labor and delivery.

Respiratory distress: Late preterm neonates require close monitoring for signs and symptoms of respiratory distress with rapid institution of supplemental oxygen and respiratory support.

Hypothermia: Recognition of the possibility of hypothermia is key. Measures that reduce the likelihood of hypothermia are drying of the skin and scalp, application of warm blankets, skin-to-skin contact with mother and later swaddling with warm blankets. Axillary temperature should be monitored immediately after admission and every 4 hours during the hospital stay. The infant should demonstrate stable temperature in an open crib before discharge.

Hypoglycemia: It is important to anticipate, recognize, and treat neonatal hypoglycemia. Irrespective of the mode and place of care—whether in the newborn nursery, rooming with the mother or in the intensive care unit, infant’s serum glucose must be monitored.

Feeding difficulties: Pediatricians need to be alert to suboptimal breast-feeding in late preterm neonates and not be misled by the seemingly satisfactory initial breast-feeding prior to hospital discharge. Experienced nurses should evaluate suck-swallow coordination, evaluate for feeding fatigue and offer lactation consultation. Feeding volume and frequency may need to be altered accordingly.

Hyperbilirubinemia: The best clinical way to avoid marked hyperbilirubnemia is prevention. This includes parental education, screening for jaundice, provision of lactation support, timely post-discharge follow-up and treatment as indicated. Serum bilirubin should be measured at 24 hours followed by visual assessment for jaundice in hospital every 8-12 hours. Parents should be educated to look for worsening jaundice, poor feeding, decreased activity and decreased urine output. Infants should be seen by an experienced provider 1-2 days after discharge.

What are the possible outcomes of late preterm birth?

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. They require resuscitation at birth almost twice as often as term infants. Late preterm neonates are two to four times likely to have severe jaundice when compared with term infants and are more likely to require phototherapy. They are susceptible to cold stress and are more likely to have problems with feeding.

Late preterm infants are also more likely to be developmentally delayed and more likely to be referred for special needs preschool resources. They are more likely to have problems with school readiness and problems during school. The brain at 34 weeks of gestation weighs only 65% of the term brain. Myelination is incomplete and gray matter volume increases rapidly between 36 and 40 weeks of gestation. Recognition that the brain is only 65% of term weight at 34 weeks underscores vulnerability to insults that interfere with basic mechanisms of myelination and neuronal and glial maturation.

Given the large numbers of late preterm infants, the economic and social risks posed by the late preterm delivery are substantial.

What causes late preterm birth 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 include the increasing proportion of women choosing to have babies later in life with associated complications of pregnancy that require early delivery, increased demand for assisted reproduction and an increased incidence of multiple gestations. 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?

Although preterm delivery may be necessary to protect either mother or fetus, in the absence of clear indications, elective delivery should be avoided prior to 39 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 to mother and infant.

What is the evidence?

Gyamfi-Bannerman, C, Thom, EA, Blackwell, SC. "Antenatal betamethasone for women at risk for late preterm delivery". N Engl J Med. vol. 374. 2016 Apr 7. pp. 1311-20.

(The documents reduction in respiratory morbidity in women receiving antenatal betamethasone prior to late preterm delivery.)

Kamath-Rayne, B, Rozance, PJ, Goldenberg, RL, Jobe, AH. "Antenatal corticosteroids beyond 34 weeks gestation: what do we do now". Am J Obset Gynecol. vol. 215. 2016. pp. 423-30.

(This critical review urges caution before wide-scale adoption of a treatment focused primarily on the lung. Infants born prior to term remain at risk of long-term neurodevelopmental morbidity and other adverse consequences of late preterm birth.)

Kugelman, Colin, AA. "Late preterm infants: near term but still in a critical developmental time period". Pediatrics. vol. 132. 2013. pp. 741-71.

(Excellent review of long-term neurodevelopmental and respiratory complications of preterm birth.)

"American College of Obstetrician and Gynecologist. Medically indicated late-preterm and early-term deliveries. Committee Opinion No. 560". Obstet Gynecol. vol. 121. 2013. pp. 908-10.

"American College of Obstetricians and Gynecologist. Nonmedically indicated early-term deliveries. Committee Opinion No. 561". Obstet Gynecol. vol. 121. 2013. pp. 911-5.

(These articles clarify the position of ACOG on indications for late preterm delivery.)

Engle, WA, Tomashek, KM, Wallman, C. "Committee on Fetus and Newborn, American Academy of Pediatrics. “Late-preterm” infants: a population at risk". Pediatrics. vol. 120. 2007. pp. 1390-1401.

(This states the position of the AAP regarding complications and management of late preterm birth.)

Ongoing controversies regarding etiology, diagnosis, treatment

Parents and physicians should be aware that infants who are delivered at late preterm gestational ages have higher risks for early morbidities and mortality as well as increased long-term pulmonary and developmental morbidities. Recent studies support prenatal corticosteroids to reduce pulmonary complications of late preterm birth. While this is attractive in the short-term, it should not facilitate delivery prior to 39 weeks without clear maternal or fetal indications. Prenatal corticosteroids do not decrease, and without long-term follow-up cannot be assumed not to increase, neurodevelopmental impairment.

**The original authors for this chapter were Drs. Karen Hendricks-Munoz and Pradeep Mally. The chapter was revised by Drs. Pradeep Mally and M. Douglas Jones.

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