Sections

Prematurity

Treatment

Approach Considerations

Consultations

In cases of prematurity, consider consulting with a developmental specialist. The risk of neurodevelopmental problems occurs as gestational age and birth weight decrease.

Hearing screening should be performed on all newborns before they are discharged.

Transfer

Transferring premature infants to a center that specializes in the care of high-risk mothers and infants improves outcomes because of the availability of resources and experience. Transfer can help in addressing neonatal issues of intravenous support and oxygenation and/or mechanical ventilation. It also provides access to pediatric subspecialists.

Consider transport and/or insurance costs of reverse transfer. Such transfer may permit the family to be near the patient and to establish a family support system. Reverse transfer may extend goodwill to the referring hospital (and forge ties to the regional neonatal intensive care unit [NICU]) and promote continuity with the referral physician for discharge. This may improve the experience of local hospital staff. This may help in decompressing the regional NICU. Reverse transfer may aid in addressing social service concerns.

Automated versus manual oxygen control

Studies have demonstrated automated oxygen control improves oxygen saturation targeting across different saturation ranges in premature infants on noninvasive and invasive respiratory support.^{[36, 37, 38, 39]}However, whereas some studies show automated oxygen control reduces hypoxemia and hyperoxemia,^[40]others show a reduction in hypoxemia,^{[37, 38]}or in hyperoxemia but not hypoxemia.^[39]Preliminary adaptive algorithms for automated oxygen control in these patient populations have also been developed and show promise.^{[41, 42]}

Surgical Care

Premature infants generally do not require surgical care except when they develop complications (eg, hemodynamically significant patent ductus arteriosus) or require gastrostomy tube placement for oral feeding difficulties.

Medical Care

Stabilization in the delivery room with prompt respiratory and thermal management is crucial to the immediate and long-term outcome of premature infants, particularly extremely premature infants. The American Academy of Pediatrics (AAP) has established guidelines for levels of neonatal care.^[43]

Principles of respiratory management are as follows:

Recruit and maintain adequate lung volume or optimal lung volume. In infants with respiratory distress, this step may be accomplished with early continuous positive airway pressure (CPAP) given nasally, by nasal mask, or by using an endotracheal tube when ventilation and/or surfactant is administered.
Avoid hyperoxia and hypoxia by immediately attaching a pulse oximeter and keeping the oxygen saturation (SaO₂) between 90% and 95% by using blended oxygen. The lower limits of the pulse oximeter alarm should be set closer to the lower saturation limit, and the upper alarm limit should be no more than 95%.^[4]
Prevent/minimize barotrauma or volutrauma by using a ventilator. Permissive hypercapnia on an individualized protocol can lead to better respiratory outcomes. Normal tidal volume is 4-7 mL/kg.
Administer surfactant early (age < 2 hours) when indicated. Routine use of prophylactic surfactant solely for prematurity is not advisable.

Many centers use early CPAP and have a relatively permissive approach to ventilation. Avoidance of mechanical ventilation or endotracheal tube placement is a welcome step. Efforts should be made to use CPAP as a first line of respiratory support if infant has spontaneous respiration.

A retrospective analysis that studied the first 48 hours in 225 infants of 23-28 weeks' gestational age found that clinical history or initial blood gas results were poor predictors of subsequent nasal CPAP failure.^[44]Of the 225 infants, 140 could be stabilized with nasal CPAP in the delivery room; 68 with a favorable outcome and 72 with a failed outcome within 48 hours. The investigators noted that a threshold fraction of inspired oxygen (FiO₂) of 0.35-0.45 or greater compared with 0.6 or above for intubation may shorten the time to surfactant delivery, without a relevant increase in intubation rate.^[44]

In select extubated preterm infants, nasal cannulae appears to be comparable to CPAP. In a multicenter, randomized, noninferiority study, Manley and colleagues reported that in extubated preterm infants with a gestational age of at least 26 weeks but less than 32 weeks, breathing support using high-flow nasal cannulae (HFNC) was comparable to that using nasal CPAP.^[45]Results were derived from 303 extubated preterm infants who were treated with HFNC (151 infants) or CPAP (152 infants).

During the 7 days following extubation, the failure rate was 34.2% in the HFNC group and 25.8% in the CPAP group.^[45]However, the reintubation rate in the infants treated with HFNC (17.8%) was lower than in the CPAP group (25.2%), because half of the infants in whom HFNC failed were successfully treated with CPAP. The nasal trauma rate was 39.5% in the HFNC group and 54.3% in the CPAP group.^[45]

In January 2014 the AAP released a policy statement on respiratory support for newborn preterm infants.^{[46, 47]}Management of these preterm infants must be individualized, and the healthcare setting and team must be considered. The AAP recommendations also include the following^{[46, 47]}:

Early use of CPAP with subsequent selective use of surfactants: Compared with routine intubation with prophylactic or early surfactant therapy, early postnatal CPAP in extremely preterm infants reduces the rates of bronchopulmonary dysplasia and death
If mechanical ventilation is necessary: Early administration of surfactant and then rapid extubation is preferable to prolonged ventilation

The AAP notes that early CPAP alone does not increase the risk for adverse outcomes if surfactant therapy is either delayed or not administered.^{[46, 47]}Moreover, early administration of CPAP may reduce the duration of mechanical ventilation and postnatal corticosteroid therapy.

Thermoregulation

Maintenance of the neutral thermal environment is critical for minimizing stress and optimizing growth of all newborns, but especially for premature infants. The neutral thermal environment is defined as the environmental temperature in which the neonate maintains a normal temperature and is consuming minimal oxygen for metabolism.

Use radiant warmers with skin probes to regulate the desired temperature (in general, a normal body temperature of 36.5º-37.5ºC [97.7º-99.5ºF]^[5]). A heated and humidified isolette is ideal for extremely low birth weight (ELBW) infants. Food-grade plastic wrap/sheets can also be very helpful immediately after birth to control humidity and prevent heat loss in ELBW infants. The environmental temperature should be maintained to at least 25ºC (77º F).^[5]

Neonates lose heat by four means, as follows^[5]:

Evaporation: Evaporation is energy consumed by a fluid as it converts from a liquid to gas. This is primarily in the delivery room. Completely drying the infant is of primary importance in prevention of hypothermia. This step can be omitted if other resuscitative measures are taking place.
Conduction: This is direct transfer of heat from a warm body to a cool object by contact (eg, placing an infant on a cold scale).
Convection: This is the loss of heat from the warm air next to the skin to moving air currents (eg, windchill effect). Double-walled isolettes help to reduce convective heat loss.
Radiation: This is the loss of heat that radiates from a warm body to a cool surface (eg, window, outside wall).

Preterm infants are relatively unable to compensate for cold stress because they have only a small amount of subcutaneous tissue (insulation) and decreased brown fat to produce heat. Note that preterm infants do not shiver. The increased surface area to body mass allows for rapid heat loss, especially from the head. Decreased posturing ability further diminishes their ability to compensate.

In ELBW infants, immature skin further complicates thermoregulation due to increased evaporative water loss. (See Extremely Low Birth Weight Infant.)

Consequences of cold stress are increased metabolism with loss of weight or failure to gain weight and increased use of glucose with depletion of glycogen stores and hypoglycemia.

Metabolic acidosis results in decreased surfactant production and loss of functional alveolar numbers, which results in hypoxia. The hypoxia causes pulmonary vasoconstriction and further hypoxia. Increased oxygen consumption results in hypoxia, anaerobic metabolism, and lactic acid production.

In the intensive care nursery, radiant warmers may be used to compensate for heat loss. Incubators are more efficient than radiant warmers because the heated environment decreases heat loss due to conduction, convection, and radiation. With radiant warmers, consider using food-grade plastic wrap/sheets and a humidified environment for ELBW infants. New devices function as both an incubator and an overhead warmer to enable access for procedures. In all nurseries, maintain the environmental temperature above 23º-25ºC (>74º-77ºF).

Temperature maintenance is especially critical during neonatal resuscitation, when the same principles apply. (See Neonatal Resuscitation).

Skin care

Premature infants have immature skin, a decreased or absent stratum corneum, decreased cohesiveness between skin layers, increased water fixation, and tissue edema. The immature skin integrity leads to easy injury, transdermal absorption of drugs and other materials in contact with the skin, and increased risk for infection.

The National Association of Neonatal Nurses (NANN) and the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) recommended the following areas of newborn skin care, which are based on clinical and laboratory research:

Bathing: Use only water and no soap for infants who weigh less than 1000 g. Decrease the frequency of using cleansers. Only use neutral-pH cleansers.
Disinfectants (eg, povidone-iodine, chlorhexidine): Completely remove these agents after the procedure to decrease transdermal absorption. Isopropyl alcohol use is discouraged because it is relatively ineffective as a disinfectant and is drying to the skin. Alcohol burns, and cracked skin can result.
Adhesives: Minimize the use of adhesives. Use double-backed silk tape versus tape with strong adhesive properties (eg, Elastoplast). Use hydrogel electrodes. Avoid solvents or bonding agents.
Transepidermal water loss: Place infants born at 30 weeks' gestation in a high-humidity (>70%) environment.
Topical solutions: Review ingredients of any topical solution placed on the skin of a preterm infant. Transdermal absorption can occur. Discourage use of solvents for adhesive removal.
Pectin barriers (eg, DuoDERM extra thin, Restore extra thin): Pectin barriers are recommended. Anchoring devices (umbilical lines) to pectin barriers results in improved skin integrity.

Fluid and electrolyte management

Preterm infants require intense monitoring of their fluid and electrolyte levels because of their increased transdermal water loss, immature renal function,^[6]and other environmental issues (eg, radiant warming, phototherapy, mechanical ventilation). The degree of prematurity dictates the initial fluid management. The following are general principles of fluid and electrolyte management when caring for premature infants:

The initial fluid should be a solution of glucose and water.
Calcium may be added in the initial fluid.
Total parenteral nutrition should be started as early as possible, especially for extremely low birth weight (ELBW) infants.

Expected loss of extracellular water in the first week of life in term infants is 5% of birth weight; 10% of birth weight in low birth weight (LBW) infants; and 15-20% of birth weight in ELBW infants. Data curves, which Dancis developed in the 1940s, may be useful in monitoring weight loss in each group of infants.

The degree of prematurity and the infant's specific medical issues dictate initial fluid therapy. However, the following general principles apply to all preterm infants:

Initial fluids should be a solution of glucose and water. More mature infants can be started at 60-80 mL/kg/d. The most immature infants may need up to 100-150 mL/kg/d. (See Extremely Low Birth Weight Infant.)
Environmental aspects of care (eg, radiant warmer, phototherapy, and a nonhumidified environment) increase insensible water loss and the need for more fluids. Mechanical ventilation, use of double-walled isolettes, and provision of humidity decrease insensible water loss.
The glucose infusion rate (GIR) is usually started at 4-6 mg/kg/min. In general, to obtain this rate, a solution of dextrose 10% in water (D10W) should be used initially. The exception is the ELBW infant who should initially be given dextrose 5% in water (D5W) to provide the same GIR and to prevent hyperglycemia.
Electrolytes should not be added until 24 hours of age, when urine output is adequate. Electrolyte and calcium levels should be monitored at 12-24 hours of age depending on the degree on prematurity and other medical issues.
Basal needs are sodium is 2-3 mEq/kg/d, potassium 1-2 mEq/kg/d, and calcium 600 mg/kg/d (as calcium gluconate). Urinary losses, which may increase in the most immature of infants and in those exposed to diuretics, dictate the need for supplemental sodium.
Infants who develop acute tubular necrosis (ATN) should be treated with fluid restriction that equals insensible water loss plus urine output. Additional fluid is administered by closely and frequently monitoring the output and electrolyte levels during the post-ATN diuretic phase.
Hyponatremia and weight gain should be treated with decreasing fluid administration. Monitoring of urinary electrolyte losses is sometimes helpful in replacement therapy.
The infant's weight should be followed up every 24 hours. Results of laboratory monitoring, urine output and change in weight dictate changes in fluid and electrolyte support.

Evidence-based guidelines

In a study of 160 very LBW infants (≤1250 g), the introduction of evidence-based guidelines focusing on preventing heat loss, reducing exposure to supplemental oxygen, and increasing the use of noninvasive respiratory support led to significantly improved outcomes.^{[48, 49]}Average admission temperatures increased (36.4°C vs 36.7° C), and the percentage of infants admitted with moderate or severe hypothermia decreased (14% vs 1%). Exposure to oxygen decreased during the first 10 minutes of life, whereas oxygen saturations remained similar.^{[48, 49]}

Decreases were also observed in the median duration of invasive ventilation procedures (5 days vs 1 day) and the duration of hospital stay (80 vs 60 days) after the guidelines were introduced.^{[48, 49]}

Kangaroo mother care

A multistakeholder group of newborn health advocates proposed accelerating global kangaroo mother care (KMC) as the standard of care for preterm infants.^{[50, 51]}KMC consists of various preterm infant care practices that include skin-to-skin contact, breastfeeding, and close postdischarge follow-up. According to the advocacy group, achieving universal KMC coverage could potentially save an estimated 450,000 preterm newborns annually, but current global coverage of KMC is lower than 1%.^[50]With a goal of achieving 50% coverage of KMC by the year 2020, the group planned a series of actions, including revising the World Health Organization KMC guidelines, incorporating high-quality KMC into national policies, conducting more research, and engaging health professional associations.^[50]

Studies in multiple resource-poor areas indicate that KMC coverage has improved, but has fallen short of the 50% goal. Government leadership, healthcare implementation, standardized tracking and reporting systems, and social and cultural support are needed to fully achieve the benefits of KMC.^{[52, 53, 54]}

Dexamethasone may affect hearing and intelligence in preterm infants

A meta-analysis indicated that dexamethasone use in preterm infants may have significant deleterious effects on hearing and intelligence.^[55]The study looked at 10 randomized, controlled trials involving a total of 1038 preterm infants, including 512 who received intravenous dexamethasone and 526 who received a placebo. The investigators found a significantly lower intelligence quotient in patients who received dexamethasone treatment within 7 days following birth, relative to the placebo group.^[55]

In infants who began treatment with dexamethasone more than 7 days after birth, the incidence of hearing loss was significantly greater than in the control group, although the change in intelligence quotient was comparable to that in the placebo group. The investigators also found that the incidence of cerebral palsy and visual impairment were similar in the dexamethasone and placebo groups whether dexamethasone was received within 7 days following birth or later.^[55]

Discharge criteria

Perform developmental assessment and intervention, as appropriate.

Discharge criteria in cases of prematurity are as follows:

The parents and/or caregivers are capable. That is, they demonstrate an ability to meet the needs of the infant.
The patient's caloric intake is adequate for growth.
The patient has been weaned from the supplemental heat.
Medical problems are defined and manageable at home.
No apnea or bradycardia is present for some time.

Diet

Preterm infants born at less than 35 weeks' gestation have poor coordination of the suck and swallow reflexes and decreased intestinal motility. Nutrition in the first several days after birth often is provided intravenously. Even the relatively healthy preterm infant may not reach full enteral nutrition until a week or longer after birth.

In a study of nearly 700 premature infants receiving parenteral therapy, researchers found that chromium supplements (0.2 mcg/kg/day) in the first week of life improved glucose tolerance and calorie absorption.^[56]These benefits were also observed in very low birth weight infants. In the study, rates of hyperglycemia were similar in infants who received chromium supplements and those who did not. At similar hyperglycemia levels, infants treated with chromium tolerated significantly higher mean glucose infusion rates (8.4 vs 8 mg/kg/min) and significantly greater daily mean parenteral calorie intake (74.8 vs 71.5 kcal/kg/day).^[56]

In a review of 15 studies comprising 979 infants, investigators found similar safety and efficacy between newer lipid emulsions (LE) from alternative lipid sources with reduced polyunsaturated fatty acid (PUFA) content and that of conventional pure soybean oil-based LEs that have high PUFA content for the parenteral nutrition of preterm infants.^[57]There were no statistically significant differences in clinically important outcomes including death, growth, bronchopulmonary dysplasia, sepsis, retinopathy of prematurity of stage 3 or higher, and parenteral nutrition-associated liver disease with the use of newer alternative LEs versus the conventional pure soy oil-based LEs.

Colostrum

If available, colostrum is the preferred initial nourishment. Colostrum contains digestible proteins, antibody (secretory immunoglobulin A [IgA]), growth factors, and other components that in the aggregate promote intestinal villous growth and influence the intestinal colonization.

Mature breast milk

Mature breast milk replaces transitional milk by 10-12 days after birth. The caloric density varies among mothers based in part on the mother's nutritional status. Note that for ELBW infants, breast milk is often inadequate to sustain growth.

Most calories are contained in lactose (35%) and fat (50%). In the more preterm infants, lactase activity is low which may contribute to less-than-optimal digestion of lactose and absorption of carbohydrate. This improves with gestational age.

Calcium, sodium, potassium, and trace mineral levels in breast milk are insufficient to meet the needs of the preterm infant. Therefore, minerals, protein, carbohydrates, and lipids are often added to breast milk to support optimal growth in the form of commercially available breast milk fortifiers.

Approximately 120-150 cal/kg/d are required for growth. Small preterm infants with increased metabolic needs due to complications such as bronchopulmonary dysplasia may require as much as 180 cal/kg/d to grow.

Formula

Preterm formulas have been developed to address the specific needs and digestive abilities of the preterm infant. The typical formula contains more easily digested glucose polymers (50% of carbohydrates) and medium chain triglycerides that minimize the need for active lipase activity.

Although preterm formula contains more calcium and phosphorus than breast milk, osteopenia of prematurity and poorly mineralized primary teeth remain clinically significant problems.^[51]Poor early intravenous nutrition and the use of diuretics often exacerbate these problems. Increased sodium compensates for poor renal retention. Exercise has an important potential role for preventing and treating osteopenia of prematurity.^[51]

The formulas contain additional trace minerals and vitamins.

Dietary guidelines

Guidelines issued in 2013 by the American Academy of Pediatrics offer the first dietary recommendations for vitamin D and calcium intake specifically for preterm infants.^{[58, 59]}Bone mineral requirements of preterm infants differ significantly from those of full-term babies. The guidelines recommend 200-400 IU of vitamin D daily for preterm infants with very low birth weight (VLBW) (ie, < 1500 g). When the infant's weight rises above approximately 1500 g and the baby can tolerate full enteral nutrition, an increase to 400 IU/day is advised.

To prevent rickets in preterm infants, the guidelines also recommend that high amounts of mineral supplements be used in infants who weigh less than 1800-2000 g.^{[58, 59]}Supplementation should include human milk fortified with minerals or infant formulas designed specifically for preterm infants and should be based on infant weight rather than gestational age.

Long-Term Monitoring

Extremely low birth weight (ELBW) and very low birth weight (VLBW) infants require close monitoring of their neurodevelopmental progress. Early identification of developmental concerns and appropriate intervention leads to better outcomes. Anticipatory guidance must be given to parents or caregivers to achieve the best possible outcome.

Premature infants require close monitoring of nutrition, growth, and development on a regular basis by the pediatrician. ELBW infants and infants with complications need to see a developmental specialist to identify concerns early on to provide appropriate therapies. Pediatric dietitian consult is indicated if nutrition issues arise.

Medication

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Media Gallery

Preterm infant at 28 weeks' gestation. Note the small amount of ear cartilage and/or flattened pinna.
Preterm infant at 33 weeks' gestation. Note the increased cartilage, recoil, and outer ridge curving inward.
A term infant has well-developed cartilage with instant recoil.
Preterm infant at 28 weeks' gestation. Note the flat sole.
Preterm infant at 33 weeks' gestation. Note the presence of only an anterior crease.
Term gestation. Note the multiple creases.
Preterm infant at 28 weeks' gestation. No breast tissue is present, and the areolae are barely visible.
Preterm infant at 33 weeks' gestation. The breast tissue is less than 1 cm, and the areolae are raised and/or pigmented.

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Author

Susan A Furdon, RNC, NNP-BC, MS Neonatal Clinical Nurse Specialist/Nurse Practitioner, Department of Pediatrics, Albany Medical Center

Susan A Furdon, RNC, NNP-BC, MS is a member of the following medical societies: National Association of Neonatal Nurses, Sigma Theta Tau International

Disclosure: Nothing to disclose.

Coauthor(s)

David A Clark, MD Professor and Martha Lepow Chairman of Pediatrics, Professor of Obstetrics and Gynecology, Albany Medical College; Director, Children's Hospital at Albany Medical Center

David A Clark, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Forestry Association, American Pediatric Society, Capital District Pediatric Society, Christian Medical and Dental Associations, European Society for Paediatric Research, Eastern Society for Pediatric Research, Floyd W Denny Pediatric Alumni Society, Medical Society of the State of New York, New York Academy of Sciences, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Arun K Pramanik, MD, DCH, FAAP, FIAP, FRCP Professor of Pediatrics, LSU Health, Louisiana State University School of Medicine in Shreveport

Arun K Pramanik, MD, DCH, FAAP, FIAP, FRCP is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, National Perinatal Association, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Dharmendra J Nimavat, MD, FAAP Associate Professor of Clinical Pediatrics, Department of Pediatrics, Division of Neonatology, Southern Illinois University School of Medicine; Staff Neonatologist, Clinical Director, NICU Regional Perinatal Center, HSHS St John's Children's Hospital

Dharmendra J Nimavat, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association of Physicians of Indian Origin

Disclosure: Nothing to disclose.

Additional Contributors

Ted Rosenkrantz, MD Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine

Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, Eastern Society for Pediatric Research, American Medical Association, Connecticut State Medical Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Prematurity Treatment & Management