DR. HUBBARD  is a newborn hosptalist pediatrician at the University of California at San Diego Medical Center.

Eustratia "Tia" Hubbard, MD

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 Pediatricians and primary care physicians

Describe the characteristics of the late preterm infant (LPI) and the specific vulnerabilities of LPIs compared with term infants

Summarize the increased risk of jaundice in the LPI and how to manage the condition to minimize negative outcomes

Identify the effect of the LPI's smaller brain on functioning and how to assist LPI families in feeding their infant

Summarize the AAP guidelines recommended for high-risk infants before hospital discharge, describe the recommended procedures for ensuring LPI safety during sleep and transport, and the need for continued follow-up care

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As birth rates for premature infants increase, we are learning that slightly premature infants (late preterm) cannot be treated the same as their term counterparts. This article reviews the definition of this unique group of pediatric patients, their characteristics and vulnerabilities, and clinical considerations to make when caring for them. 

Infants born a few weeks early have been described as "near-term," "slightly premature," and "mildly preterm." During the National Institute of Child Health and Human Development (NICHD) Workshop in 2005, an agreement was made that this group should be clearly defined. As a result, the more commonly used designation "near-term" was replaced by "late preterm," identifying those infants born between 34 and 36 6/7 weeks.

In 2005, one of every eight live-born infants was delivered at less than 37 weeks, a 20% increase from 1990.

 Much of the increase in the preterm birth rate was due to an increase in the number of infants born between 34 and 36 weeks gestation, a group which accounted for 9.1% of all singleton births in 2005.

LPIs may physically appear more like term infants than extremely premature newborns, making their unique vulnerabilities easy to overlook. During the third trimester of pregnancy, fetal organ systems from head to toe continue maturational processes in an effort to prepare the fetus for life without a placenta. Since LPIs enter the world without the last few weeks of being 

, they may be ill-equipped to manage all their new responsibilities. Fortunately, the vulnerabilities of a LPI are predictable, preventable, and manageable 

Compared to their term counterparts, LPIs have higher risks for morbidity and mortality. They experience more complications after birth, including respiratory distress, jaundice, hypoglycemia, and temperature instability. They also receive more medical therapies like intravenous infusion and sepsis evaluation.

 LPIs have higher rates of re-hospitalization than term infants, with jaundice, feeding difficulties, and dehydration being the most common diagnoses. Moreover, there is a greater risk of neonatal morbidity for LPIs who are being breastfed at discharge, are firstborn, whose mothers have had labor and delivery complications, have a mother of Asian/Pacific Islander descent, or are recipients of public insurance.

Currently, guidelines for the hospital and outpatient care of LPIs are not available, so a wide range of care practices exist. In some institutions, late preterm and term infants may be treated similarly, whereas in others LPIs may go to a neonatal intensive care unit (NICU) until they are discharged from the hospital. 

The innate weaknesses of LPIs may become evident as soon as they are exposed to air in the delivery room. Care providers can support these infants during this critical time by focusing on the processes that play a key role in the successful adaptation to life outside of the uterus-thermoregulation, energy metabolism, and respiration.

Cold stress is a frequently encountered problem with these infants. LPIs have less subcutaneous fat for insulation, an immature epidermis that is a poor barrier to evaporative heat loss, and a high surface-area-to-body-mass ratio. They have a high metabolic rate but poor substrate stores, including brown adipose tissue needed to generate heat.

If LPIs and their mothers are stable, drying of their skin and scalp with warm, dry blankets may be done while the infants are placed on their mothers' chests. Skin-to-skin contact (SSC) describes placing a baby wearing only a diaper on a caregiver's bare skin with an over-covering. Immediate and extended SSC is asso ciated with the maintenance of normal temperatures in full term and premature infants, promotion of mother-infant bonding, improved breastfeeding, reduced levels of infant crying, and less physical indicators of pain. Parents should be encouraged to keep infants in SSC or swaddled with two to three receiving blankets; a hat should remain in place. If hypothermia (less than 97.6° F or 36.5° C) is encountered, SSC or a radiant warmer may be used to normalize the temperature.

Maintenance of normal temperature helps infants regulate energy use, and thus glucose metabolism. LPIs are at increased risk for hypoglycemia because they possess less glycogen stores, and the hepatic energy pathways are immature. Therefore, infants with low birth weight or growth restriction should have a bedside glucose within one hour from birth. Additional measurements should be performed if initial hypoglycemia is detected, symptoms are ob served, or feeding is delayed or infrequent. Stable and healthy LPIs should have their first feeding within one hour of delivery. Thereafter, no more than three hours should pass between feedings.

A few weeks of immatu rity may hinder the processes of amniotic fluid clearance, maintenance of alveolar expansion, and increased lung perfusion. Compared to term infants, LPIs are more likely to encounter respiratory distress syndrome, transient tachypnea, and respiratory failure-all of which can predispose them to persistent pulmonary hypertension. Such complications may be increased when delivery is by elective cesarean without preceding labor. 

LPIs are also at increased risks for apnea of prematurity, bradycardia, apparent life-threatening events, and Sudden Infant Death Syndrome (SIDS) (1.37/1,000 births, compared with 0.67/1,000 term infant births).

 Given these risks, an observation period with cardiorespiratory monitoring may recognize problems in a seemingly healthy LPI before they are transferred into a setting where symptoms may not be detectable until a serious event occurs.

Depending on the hospital system, an LPI may be admitted to a Level II or III NICU, a Level I nursery, or directly to their mother's room for couplet care. Couplet care merges mother and baby care as a single unit, with a primary nurse caring for both. Keeping mothers and babies together from birth allows for SSC, free access to the breast, and more rapid parental learning of infant needs and cues. Admitting an LPI immediately into couplet care, however, can have its disadvantages. Because the majority of the supervision administered under couplet care is provided by the parents rather than medical professionals, the infant's risk for the problems outlined in 

 may be increased. A compromise could be to allow LPIs some SSC in the delivery room if mother and infant are stable, and then monitor the infant in a NICU or transitional nursery for the first 12 to 24 hours of life. 

These immature infants are faced with low energy stores, high energy demand, poor feeding abilities, and often a mother at risk of insufficient milk production. They are sleepy, have fewer and shorter awake periods, and easily tire with feeding. LPIs are also more likely to have a weak suck, small mouth, and uncoordinated oral-motor movements. Thus, these children may have difficulty obtaining a sufficient amount of nourishment if treated like a term infant, especially if they are exclusively breastfed. Because of these characteristics, it is imperative that LPI mother-baby pairs be competent at breastfeeding before hospital discharge. Mothers should be instructed on proper positioning and latch, as well as the importance of frequent feedings and responding to their infants' hunger cues. Nipple shields may be helpful if LPIs are not able to latch. Until birth weight is regained and milk supply well established, LPIs should have at least eight feedings in a 24-hour period.

Nurses who are caring for LPIs should be trained in how to assist breastfeeding, including how to provide supplementation with a tube at the breast  The expertise of a lactation consultant (LC) can complement these efforts, and prove to be invaluable in helping LPIs and their mothers get off to great starts. Ideally, a LC should assist with a feeding within the first 24 hours and then daily. Based on her assessments of latch, suck, and milk transfer, daily feeding plans should be developed. A card outlining this plan can be posted in the infants' bassinets for parents and nurses to follow 

Women with advanced maternal age, pregnancy-induced hypertension, infertility, significant edema, or magnesium sulfate infusion are more likely to experience delayed lactogenesis. Mothers should be encouraged to pump their breasts every two to three hours (preferably using an electric double-pump) if they experience a delay in their milk supply, or their infants have a weak suck, are receiving supplementation, or are unable to feed due to illness. 

Some LPIs may not be able to sustain themselves with exclusive breastfeeding. Infants with excessive weight loss, low metabolic reserve, poor feeding, or significant jaundice due to low intake should be supplemented. The best supplement is expressed breast milk obtained with pumping after the previous feeding, but formula or banked certified human milk are alternatives. The following volumes every two to three hours are recommended: 5 to 10 mL during the first day of life, 10 to 20 mL on day two, and 20 to 30 mL on day three; thereafter is dependent on the infant's metabolic requirements and feeding tolerance. Formulas with additional calories or fortification of human milk may be necessary if LPIs are not gaining weight on adequate volumes. 

The best way for breastfed babies to receive supplementation is during breastfeeding; this can be done using a 5 French (5 Fr) feeding tube attached to a 10-mL syringe 

 With this setup, LPIs practice proper technique to express milk while stimulating their mothers' breasts to produce. Other methods may be needed if LPIs tire quickly with suckling at the breast or their mother is unavailable. For example, holding a cup to the baby's lips to "sip" from 

 or "finger-feeding" using a 5 Fr feeding tube supported by a gloved finger inserted in the baby's mouth 

 Although the use of bottles should be avoided with breastfed babies, especially in the first few weeks, certain situations necessitate this consideration: maternal exhaustion, excessive duration of feeds, failure to grow, or poor feeding with other methods.

Parents should be informed that LPIs may need a few days more than term infants to learn how to feed, and that they may have a few great feeding sessions followed by a few difficult ones. When maternal milk is in, weighing before and after breastfeeding can help determine if adequate intake has occurred. Once LPIs have gained weight on oral feeds and are consistently feeding well, a discharge feeding plan should be created, preferably by a LC. Parents should understand how often their infant should feed, whether pumping should be continued, if supplement should be given, and if so, how much and for how long 

. Outpatient lactation resources should be provided.

An infant's bilirubin burden is dependent on the balance of bilirubin production and elimination-LPIs have issues with both. Due to an exaggerated transient ileus and low milk intake, the passage of meconium is slower, consequently increasing the enterohepatic circulation of bilirubin. Those LPI with increased red cell turnover due to hemolytic processes, G6PD deficiency, bruising, or polycythemia will produce more bilirubin. 

The activity of the bilirubin-conjugating enzyme, uridine diphosphate glucuronyl transferase (UGT), is lower in premature infants and increases with gestational age. As a result, these infants have a prolonged phase of hyperbilirubinemia. While the total serum bilirubin (TSB) is similar to that of term infants for the first four days of life, LPIs may continue to have a high value for five to seven days, such that their peak TSB is delayed. LPIs with other risk factors for impaired bilirubin conjugation, such as Gilbert's disease or Asian ethnicity, are at additional risk for severe hyperbilirubinemia.

Multiple studies have demonstrated that LPIs have problems with jaundice. These children face a seven- to thirteenfold greater risk of being readmitted for jaundice, compared to term infants.

 Moreover, an infant born at 36 weeks has a sixfold higher risk of eventually developing a TSB greater than 20 mg/dL, compared to an infant at 40 weeks.

 Kernicterus occurs more commonly among LPIs, especially those who are breastfed.

These negative outcomes in LPIs can be minimized by following several principles. The most important is optimization of feeding with the goal to increase milk intake, assist in prompt meconium clearance, increase stool volume, and prevent excessive weight loss. Keeping mothers and babies together in the hospital for four to six days will allow for more feeding assistance and observation when the bilirubin is near its peak. Obtaining a transcutaneous or TSB before hospital discharge should be considered. Many providers use a nomogram developed by Bhutani et al which reflects a normal three-day peak in bilirubin

2005;(22)5:34). Most infants in this study were term, so using this graph for LPIs could lead to an underestimation of risk. A recent publication of a transcutaneous bilirubin nomogram for infants of varying gestational ages can serve as a useful alternative.

Because LPIs are at greater risk of morbidity related to jaundice, consider starting phototherapy at a lower bilirubin level. The clinical practice guideline presented by the American Academy of Pediatrics (AAP) in 2004 included a phototherapy graph, providing different curves for infants of varying gestational age and risk.

 Once initiated, phototherapy should be continued until the TSB value has decreased. Repeating the TSB after an interval without phototherapy can identify LPIs who are still unable to independently manage their bilirubin load.

 Lastly, LPIs should be seen within a few days after discharge to evaluate for jaundice. 

Whether LPIs are at greater risk for infections due to their immature immune systems remains unknown. Nonetheless, parents should be encouraged to minimize exposure to sick contacts. Consideration of some specific infections is important.

Maternal infections may induce preterm labor or premature rupture of membranes. Testing for Group B streptococcus (GBS) colonization is performed at approximately 36 weeks, so GBS status may be unknown when LPIs are delivered. Maternal risk factors for neonatal sepsis should be reviewed, including positive or unknown GBS status, fever, prolonged rupture of membranes, chorioamnionitis, pyelonephritis, or bacteremia. Fetal tachycardia or intolerance of labor may occur with infection. If significant risk factors or any symptoms are present, blood culture and complete blood count should be obtained. Intravenous antibiotics should be started if maternal infection is known or highly suspected, symptoms of sepsis are observed, neutropenia or thrombocytopenia are present, or blood culture becomes positive. Given their set of vulnerabilities, LPIs are more frequently screened and treated for sepsis because they exhibit symptoms of possible infection, including respiratory distress, apnea, tachycardia, poor perfusion, hypoglycemia, poor feeding, lethargy, hypotonia, irritability, and temperature instability. 

The strategy for prevention of hepatitis B infection is the same for term and late preterm infants. However, infants less than 2,000 g may have a decreased response to hepatitis B vaccine (HepB) when administered before one month of age. When the maternal HBsAg status is positive or unknown, a full dose of HepB should be given within 12 hours after birth; if the infant weighs less than 2,000 g, this birth dose will not be counted and the initiation of the three-dose HepB series should begin at one month of age.

 If a mother of such a low birth weight infant is HBsAg-negative, the first dose of HepB should be postponed until one month (chronological age) or at hospital discharge. Other vaccinations may be given per the immunization schedule based on chronological age regardless of birthweight.

Prophylaxis for RSV with palivizumab or RSV-IVIG may be considered for infants born at 34 to 35 weeks gestation if the infant is younger than six months at the start of the RSV season, and two or more of the following risk factors are present: child care attendance, school-aged siblings, exposure to environmental air pollutants, congenital abnormalities of the airways, or severe neuromuscular disease. Parents of all LPIs should be counseled on the avoidance of exposure to tobacco smoke and public contact during the winter season. 

During the last six to eights weeks of gestation, more than one third of the brain volume at term is acquired, and the white matter volume increases fivefold. Significant maturation of brain structure occurs during this period of time, including increases in neuronal connections and synaptic junctions. Therefore, LPIs may be less prepared to respond to stimuli and regulate internal processes, as well as be more vulnerable to brain injury and permanent neurological disabilities. 

These infants have decreased muscle tone and are more prone to positional apnea due to airway obstruction. Moreover, their suck-swallow-breathe pattern may be disorganized compared to term infants. Due to their immature autonomic system, they may respond too briskly to stressful stimuli with rapid or lower heart rates, abnormal breathing, skin mottling, frequent startling, and regurgitation. Since the self-regulatory system of LPIs is often underdeveloped, these infants may appear irritable, indifferent, or unpredictable. They may not respond as desired to their caregivers' caresses and cooing. These behaviors should be reviewed with parents so they can develop reasonable expectations. Caregivers should be encouraged to limit the variety and frequency of stimulation; a suggestion could be to limit visitors in the first few weeks to a few family members. 

Brain growth and development will not occur in a bubble, so LPIs should experience touch, massage, gentle rocking, vibration, and singing; they should hear and see their parents. However, they may do best when they are exposed to only one of these activities at a time. Since alert periods may be sparse, breastfeeding mothers should be encouraged to keep awake infants at the breast and only "hand off" their LPIs when they are sleeping. Although preterm infants are not more likely to develop colic, if they do, the onset is typically two weeks after their expected due date. 

Systematic brain imaging of LPIs is not recommended, but a head ultrasound may be considered if there are concerning examination findings or abnormal behaviors. Prior to discharge, LPIs should undergo routine hearing screening. Follow-up with a developmental specialist may not be necessary for LPIs with uncomplicated hospital stays and normal examinations, unless concerns arise later during routine developmental assessment. 

LPIs are more likely to die from SIDS. Therefore parents of an LPI-and for that matter any parent-should be taught the tenets of SIDS prevention, the most important being that infants should be placed on their backs for sleep. Home apnea monitors are not recommended for LPIs who do not have proven apnea or heart rate abnormalities. 

Preterm babies may be at additional risk of developing deformational plagiocephaly, due to their low muscle tone or intrauterine crowding. Deformational plagiocephaly may be minimized by the practice of daily tummy time and minimizing the use of infant seats, carriers, and strollers. When transport is necessary, there are certain features of car restraints that will optimize safe positioning of an LPI 

LPIs may not have the neurological maturity to maintain their airway while positioned in a properly installed car seat. The AAP recommends that all infants less than 37 weeks gestation have an observation period in a car seat prior to hospital discharge to ensure the infant is not having apnea, bradycardia, or oxygen desaturation.

 Specific guidelines have not been detailed. More re search is needed to determine whether the information provided by a car seat challenge predicts potentially adverse events in LPIs during routine travel. At our institution, LPIs are observed on a monitor for a minimum of one hour, or the length of the car ride home. The car seat is placed at a 45° angle, and the infant secured properly. The criterion for passing this test is the absence of significant apnea, bradycardia, or desaturation. If LPIs in couplet care fail this challenge, they are transferred to the NICU for further monitoring. When LPIs fail car seat testing, but are otherwise event-free and thriving, they should be transported in a car bed.

Parents should be counseled that LPIs should never be left unattended in car seats, and should spend limited time in all devices that maintain an upright position. Handouts regarding car seat recommendations and in stallation can be found on the AAP Web site, or purchased through Safe Ride (

). A summary of safe transport approaches for parents is also provided in the 

The duration of hospitalization following delivery has been debated for decades. For LPIs, it is complicated. While the majority of these infants do not need intensive care and are healthy in appearance, they are not necessarily ready to go home after their second night. Although a shorter stay may reduce hospital-acquired morbidity and decrease separation of LPIs from parents, neonatal morbidity is increased among breastfed LPIs following early discharge. Guidelines proposed by the AAP recommend that before discharge from the hospital, high-risk infants should demonstrate a sustained pattern of weight gain, competent suckle feeding by their parents' preferred method, adequate maintenance of normal body temperature while clothed in an open bed with normal ambient temperature, and physiologically mature and stable cardiorespiratory function.

 Parents must also demonstrate their ability to supply 100% of their babies' care.

An outpatient healthcare provider should be identified soon after birth. Before LPIs leave the hospital, the first outpatient visit should be arranged for one to two days after discharge to check on weight, jaundice, and feeding. Since LPIs may continue to be sleepy and feed poorly until they reach term, they should have weekly outpatient visits to ensure adequate weight gain and sufficient maternal milk production. Mothers may need to continue pumping until their infants can demonstrate adequate feeding. 

A way to assess oral intake in the office is to weigh the clothed infant before and after breastfeeding: this requires a precise, calibrated scale and well-trained staff. A thriving LPI should gain at least 30 grams and produce five to six wet diapers a day. Obtaining a hemoglobin at the two-month visit will identify those breastfed LPIs who need iron supplementation.

Other outpatient resources, like lactation consultants and home health agencies, may be helpful in supporting the families of LPIs. For those families without funds to cover these services, arrangements can be made through the public health department for a nurse to visit the home. Some parents may also need encouragement to request help from friends and family 

There is no place as capable of making a baby bigger, stronger, and better prepared for the world as within the uterus of a healthy mother. However, until all women are able to have healthy pregnancies and carry to term, we must continue to improve the care of premature babies, including LPIs. Research specific to this newly defined group is still sparse. Several groups across the nation are attempting to formulate guidelines for the care of LPIs, including the Association of Women's Health, Obstetric and Neonatal Nurses' Near Term Infant Initiative, and the California Perinatal Quality Care Collaborative. 

1. Engle WA: A recommendation for the definition of "late preterm" (near-term) and the birth weight-gestational age classification system. 

2. Hamilton BE, Miniño AM, Martin JA, et al: Annual summary of vital statistics: 2005. 

3. Wang ML, Dorer DJ, Fleming MP, et al: Clinical outcomes of near-term infants. 

4. Shapiro-Mendoza CK, Tomashek KM, Kotelchuck M, et al: Risk factors for neonatal morbidity and mortality among "healthy" late preterm newborns. 

5. Malloy MH, Freeman Jr DH: Birth weight- and gestational age-specific Sudden Infant Death Syndrome mortality: United States, 1991 versus 1995. 

6. Maisels MJ, Kring EA: Length of stay, jaundice, and hospital readmission. 

7. Newman TB, Liljestrand P, Escobar GJ: Combining clinical risk factors with bilirubin levels to predict hyperbilirubinemia in newborns. 

8. Bhutani VK, Johnson LH, Sivieri EM: Predictive ability of predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. 

9. Maisels MJ, Kring E: Transcutaneous bilirubin levels in the first 96 hours in a normal newborn population of ≥35 weeks' gestation. 

10. American Academy of Pediatrics, Clinical Practice Guideline, Subcommittee on Hyperbilirubinemia: Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. 

11. Kaplan M, Kaplan E, Hammerman C, et al: Post-phototherapy neonatal bilirubin rebound: A potential cause of significant hyperbilirubinemia. 

12. Advisory Committee of Immunization Practices: A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States. Part 1: Immunization of infants, children, and adolescents. 

13. American Academy of Pediatrics, Policy Statement, Committee on Injury and Poison Prevention: Safe Transportation of Premature and Low Birth Weight Infants. 

14. American Academy of Pediatrics, Committee on Fetus and Newborn: Hospital discharge of the high-risk neonate-Proposed guidelines. 

Parents of LPIs have unique needs and vulnerabilities. Many perceive their infant as a smaller version of the healthy strong babies their friends have brought home, not realizing their LPI's weaknesses. Some mothers have been on bed-rest for weeks or months, and expect that once reaching 34 to 36 weeks their infants would be okay. The late preterm parent may be surprised that feeding takes so much time, and that they will need to stay in the hospital a few days longer than a term infant typically does. Parents may also be preoccupied by the stresses they experienced during the pregnancy and delivery, combined with the rigors of learning how to provide 100% of their infant's care. 

For first-time parents especially, having an infant born four to six weeks sooner than planned can be stressful. Such parents may feel unprepared because they have not attended all pre-arranged birthing and parenting classes, infant supplies have not been acquired, and the baby care books they have been reading are not completed. Since the risk for prematurity is greater for mothers who have inadequate access to care, a significant portion of parents of LPIs may have financial difficulties or a poor social support system. Therefore, a family's need for additional resources or social work involvement should be assessed during hospitalization.

Parents of healthy LPIs should be reassured that with time and attention, their baby will mature and grow. Within the first 24 hours, the vulnerabilities of LPIs and how these will be managed during the hospital stay should be reviewed with the parents. Ideally, once deemed stable, LPIs should be cared for at their mothers' bedside, allowing for unlimited SSC, promotion of breastfeeding, and parental learning of infant cues and behaviors. Parents should also be informed what requirements must be met before their LPIs can be discharged from the hospital.

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Eustratia "Tia" Hubbard, MD

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