Care of the Late Preterm Infant

Educational Objectives

The goal of this program is to improve the care of late preterm infants (LPI). After hearing and assimilating this program, the clinician will be better able to:

1. Differentiate among early preterm infants, late preterm infants, and term infants.

2. Identify health issues commonly observed in late preterm infants, with an emphasis on pulmonary immaturity, temperature instability, glucose regulation, and neurodevelopmental risk.

3. Provide supplementation that is sufficient for the nutritional needs of a late preterm infant.

Summary

Prematurity: defined as <37 wk of completed gestation (<260 days from mother’s last menstrual period)

Late preterm infants (LPI): 34 0/7 to 36 6/7 wk gestational age; accounts for 10% of live births; their size and apparent maturity can be mistaken for those of term infants (TI; >37 wk gestational age), which may lead to insufficient treatment for the LPI; do not assume an LPI is a TI

LPI vs TI: LPIs — physiologically, metabolically, and anatomically immature compared with TI; they are 3 times more likely to die in their first year of life, 6 times more likely to die in their first week of life, and 10 times more likely to die in early neonatal period as a result of maternal complications of pregnancy (eg, premature rupture of membranes, incompetent cervix, multiple gestation); higher incidence of respiratory distress, temperature instability, hypoglycemia, apnea, seizures, hyperbilirubinemia, and feeding difficulties, and higher rates of rehospitalization; after discharge within first 48 hr of life — compared with TIs, LPIs are 1.8 times more likely to be readmitted overall (likelihood increases to 2.2 times if they were solely breastfed); most common causes for readmission of LPIs are hyperbilirubinemia (jaundice) and infectious etiology, along with feeding and breathing issues and apnea; readmission — compared with infants born at 34 wk gestation, those born at 36 wk are more likely to be readmitted because they are treated as TIs (ie, discharged earlier and have higher risk for complications after discharge); 36.9% of LPIs seen in the emergency department in the first wk of life require readmission and are 2 times more likely to require admission to the intensive care unit (ICU)

Pulmonary immaturity: maternal gestational diabetes increases risk for pulmonary immaturity; in wk 34 to 36 of gestation, the terminal respiratory units evolve through the saccular stage to the alveolar stage (lungs transition into thin type-1 epithelial cells; capillaries bulge into the terminal air sacks; adult-sized surfactant pools are produced); functional immaturity — associated with delayed intrapulmonary fluid absorption and transient tachypnea of the newborn (TTN); insufficient gas exchange secondary to surfactant deficiency can cause respiratory distress syndrome (RDS; the increase in lung surface area does not occur until after the saccular lung begins to alveolarize at 38 to 40 wk gestation; prevention — prenatal steroids (given at 34 to 37 wk) facilitate surfactant production; treatment — for RDS type-1, supportive care (eg, surfactant, other types of ventilation) should be provided

Temperature instability: factors that affect response to cold stress include gestational age, infant size, maturity of the hypothalamus, and the amount of mature brown and white fat tissue; LPIs have an immature hypothalamus and cannot regulate their temperature; brown fat accumulation and maturation peak closer to term, (ie, LPIs cannot generate heat from brown tissue as effectively as TIs); LPIs have less white adipose tissue for insulation and lose heat more readily because of the larger ratio of surface area to weight; when cold-stressed, infants can become hypoglycemic and apneic; risk factors for temperature instability include chronic hypertension and preeclampsia; these patients can present with weight loss, low blood glucose, and dehydration as low body temperature suppresses hunger

Glucose regulation: if the infant presents with low glucose levels despite solely breastfeeding, formula or intravenous (IV) fluids should be provided in the ICU; plasma glucose levels drop significantly in the first few hours of life following the stress of delivery; hypoglycemia — incidence is inversely proportional to gestational age (LPIs have higher risk); contributing factors include immature hepatic glycogenolysis, immature adipose tissue lipolysis, deficient hepatic gluconeogenesis and ketogenesis, insufficient glycogen stores, and feeding difficulties; significantly low levels of glucose can affect brain development; breastfed TIs can tolerate low blood glucose because they have more fat and produce ketone bodies that protect the brain, which LPIs struggle to do; hypoglycemia in LPIs is most likely caused by immature glucose regulatory mechanisms; hypoglycemia requiring continuous glucose infusion rate (CGIR) occurs more frequently in LPI than TI (15.6% vs 5.3%); CGIR protects brain development during transition from IV fluids to feeding

yperbilirubinemia: may be associated with breastfeeding jaundice; monitor bilirubin levels over the first 96 hr of life (serum bilirubin rises over first 2-3 days of life, then peaks by 4 to 5 days); compared with TIs, LPIs are 2.4 times more likely to develop hyperbilirubinemia; LPIs have lower levels of uridine diphosphate glucuronosyltransferase (UDPT) and delayed maturation (cannot conjugate bilirubin loads as fast); UDPT activity increases after 40 wk, but delayed enzyme production increases the risk for hyperbilirubinemia; LPIs have immature gastrointestinal function paired with feeding difficulties, which leads to increased enterohepatic circulation, decreased stooling, and dehydration; LPIs have immature blood-brain barriers and lower albumin levels, increasing risk for complications from hyperbilirubinemia

Neurodevelopment in LPI: the brain at 35 wk gestation weighs two-thirds of that at 40 wk; removing an infant from the optimal placental environment for the last 4 to 5 wk of brain development increases risk for detrimental outcomes; magnetic resonance imaging and cerebral volumes — at 24 to 25 wk gestation, the developing brain is smooth; at 38 to 40 wk, the brain has developed gyri and sulci, and the infant has increased cerebral volume and cortical surface area (compared with infants at 34-35 wk); neurodevelopment at 34 to 40 wk — 50% of increase occurs in this time period; distribution of cellular components is altered with increasing brain volume; cellular growth of the brain increases as gestational age increases; myelinated white matter develops after 30 wk gestation and increases 5-fold by 40 wk gestation; gray matter increase exponentially at a rate of 1.4%/wk of gestation; impact on LPI — apnea of prematurity observed at 35 to 36 wk (LPI may require caffeine and monitoring); immature suck-swallow reflex can cause apnea, breathing issues, and feeding difficulties; hypothalamic immaturity causes temperature instability, in which the infant becomes cold, does not eat, and may stop breathing; increased risk for seizures (they are more susceptible to hypoxic brain injury); sudden infant death syndrome; learning disabilities — LPIs have higher risk for learning disabilities, but etiology is unknown; one study found risk for developmental delay and disabilities was higher in LPIs than TIs, and prekindergarten LPIs had increased risk for needing special education and being suspended; parents can reduce this risk by breastfeeding, keeping the infant warm, and focusing on the child’s education

Nutritional needs: LPIs — have nutritional requirements that predispose them to higher rates of morbidity and hospital readmission; have increased risk of being underweight and stunted at 12 to 24 mo of age; feeding difficulties — prevent consumption of adequate nutrition and induce immediate caloric deficits; poor oral-motor tone, function, and neural maturation predisposes LPIs to dehydration and hyperbilirubinemia; infants are often discharged before lactation is established and can have issues with latching and milk transfer; considerations — LPIs require more protein, calcium, and phosphorus because of higher energy expenditure; maternal breastmilk may not be sufficient; mineral requirements are high in infants born at <40 wk; bone mineralization lags bone growth because bones contain smaller mineral stores (greater need for calcium and phosphorus); placental transfer of long-chain polyunsaturated fatty acids, iron, and trace elements is terminated following birth; intake needs to mirror the preterm requirement (no data to justify difference in nutrition amount from breastmilk vs placenta); universal feeding guidelines are difficult to establish because of growth and feeding variability

Recommendations: LPIs weighing <2500 g at birth (<37 wk gestation) need nutrient-enriched supplementation for the first 6 to 9 mo of life to reduce risk for readmission, feeding difficulties, and poor neurodevelopmental outcomes, and improve quality of growth (lower fat adiposity and increased fat-free mass); the goal is to develop a lean body with adequate fat stores and protein to promote body and brain growth; fortify the breastmilk after feeding and supplement with 1 to 2 bottles of nutrient-rich formula (eg, NeoSure, Enfamil, Similac) to increase calories, protein, minerals, trace elements, and long-chain polyunsaturated fatty acids; supplementation should continue until the infant is 52 wk postconceptional age; start multivitamin with iron at 2 wk of age for first year of life unless the infant is consuming >1 L of formula per day; for LPIs with birth weight <2.5 kg (34 to 37 wk gestation), provide 24 kcal supplementation, then decrease to 22 kcal when they reach 25th to 50th percentile; if birth weight is >2.5 kg, provide 22 kcal formula until the infant is 6 to 9 mo of age

Readings

Basso O, Wilcox A. Mortality risk among preterm babies: immaturity versus underlying pathology. Epidemiology. 2010;21:521-527; doi:10.1097/EDE.0b013e3181debe5e; Battarbee AN et al. The association of pregestational and gestational diabetes with severe neonatal morbidity and mortality. J Perinatol. 2020;40:232-239; doi:10.1038/s41372-019-0516-5; Garg M, Devaskar SU. Glucose metabolism in the late preterm infant. Clin Perinatol. 2006;33:853-870; doi:10.1016/j.clp.2006.10.001; Hay WW Jr et al. Energy requirements, protein-energy metabolism and balance, and carbohydrates in preterm infants. World Rev Nutr Diet. 2014;110:64-81; doi:10.1159/000358459; Lemola S et al. Effects of gestational age on brain volume and cognitive functions in generally healthy very preterm born children during school-age: A voxel-based morphometry study. PLoS One. 2017;12(8):e0183519. Published 2017 Aug 29. doi:10.1371/journal.pone.0183519; Ramachandrappa A, Jain L. Health issues of the late preterm infant. Pediatr Clin North Am. 2009;56; doi:10.1016/j.pcl.2009.03.009; Ray KN, Lorch SA. Hospitalization of early preterm, late preterm, and term infants during the first year of life by gestational age. Hosp Pediatr. 2013;3:194-203; doi:10.1542/hpeds.2012-0063; Shapiro-Mendoza CK et al. Risk factors for neonatal morbidity and mortality among “healthy,” late preterm newborns. Semin Perinatol. 2006;30:54-60; doi:10.1053/j.semperi.2006.02.002; Su BH. Optimizing nutrition in preterm infants. Pediatr Neonatol. 2014;55:5-13; doi:10.1016/j.pedneo.2013.07.003; Watchko JF. Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol. 2006;33(4):839-ix. doi:10.1016/j.clp.2006.09.002.

Disclosures

For this program, members of the faculty and planning committee reported nothing to disclose. 

Acknowledgements

Dr. Saxonhouse was recorded exclusively for Audio Digest using virtual teleconference software, in compliance with current social-distancing guidelines during the COVID-19 pandemic, on July 23, 2020 and December 11, 2020, respectively. Audio Digest thanks the speakers for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

PD671601

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.