Summary

Rates of prematurity are rising in the United States, principally due to rising rates of late preterm delivery. In 2005, 12.7% of all births occurred prematurely, or prior to 37 weeks gestation, with 87% of premature births occurring between 32 and 37 weeks.[1] Whereas extremely preterm infants are often discharged from the neonatal intensive care unit (NICU) with multiple follow-up appointments, larger preterm infants often receive follow-up solely from their pediatricians. Because of this, it is important for all pediatricians to be knowledgeable about the health and developmental problems associated with prematurity. Problems associated with prematurity, such as poor growth and developmental delays, are not exclusive to extremely preterm infants and can be seen (albeit with lower incidence) at all gestational ages. The purpose of this article is to acquaint pediatricians with the most common needs of preterm infants after discharge and to review the most recent guidelines for preterm infant care. Areas to be discussed include nutrition, growth, immunization, and developmental care.

Educational objectives

At the conclusion of this activity, participants will be able to:

• Describe the concepts of corrected and chronological age as they pertain to assessment of growth and development of the preterm infant
• Describe the use of vitamins and iron in preterm infants after discharge
• Formulate a timeline for developmental assessment of preterm infants in the general pediatric office

CME credit

This is an article from The Child's Doctor, Spring 2008 issue. You may take the quiz for learning purposes, but credits are no longer valid.

Author disclosures

Dr. deRegnier has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

Dr. Machut has no industry relationships to disclose and does not refer to products that are still investigational or not labeled for the use in discussion.

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Age correction

When evaluating growth and development in preterm infants, it is necessary to correct or adjust the infant's age to evaluate progress. Using the corrected age, most preterm infants show normal patterns of growth and development. To compute the corrected age, the months of prematurity (1 month for every 4 weeks less than 40 weeks estimated gestational age) are subtracted from the chronological age. For example, a 6-month-old boy born at 28 weeks gestation would be 3 months corrected age and would be expected to have the growth and development of a 3-monthold child. There is no widespread agreement regarding when to stop using corrected age, but for infants born at less than 32 weeks gestation it is common to correct the age through 2 years.

Growth and nutrition

Early nutrition in preterm infants is important for growth, bone mineralization, and development. Although nutritional management in the NICU is improving, growth and nutritional assessments still do not match intrauterine standards at the time of discharge for the majority of infants. In particular, it is difficult to provide adequate amounts of protein, calcium, and phosphorus to mimic in utero accretion rates. Catch-up or accelerated growth generally occurs following discharge. By 20 months of age, 76%–82% of very low birth weight boys and girls have normal growth percentiles for chronological age,[2] with continued normalization occurring through the first decade. Ongoing poor growth may occur in infants with ongoing problems, such as chronic lung disease, gastroesophageal reflux, and severe neurologic impairments. Infants who were small for gestational age at birth are also at risk for poor growth the first years after discharge.

The best way to promote nutritional recovery and optimal growth is currently very controversial. It is accepted that many preterm infants have nutritional deficits at discharge from the hospital, requiring remediation. Infants with subnormal growth percentiles will not achieve normal size without catch-up growth and indeed, catch-up growth appears to be a biologically programmed activity that occurs with all diets. However, there are increasing concerns that growth that is too rapid during infancy may be associated with long term health problems, such as the metabolic syndrome. Not only is there controversy regarding how rapidly preterm infants should grow after discharge, there is also controversy regarding dietary choices. At this time, no diet has proven to be resoundingly superior in correcting nutritional deficits or promoting growth in preterm infants and therefore, dietary choices after discharge should be individualized according to the availability of breast milk, maternal preferences, infant feeding abilities, and specific nutritional needs.

Dietary choices for preterm infants include human milk, standard infant formula and transitional formula. Human milk is the optimal nutrition for full term infants and has many benefits for preterm infants as well. Studies conducted during the NICU stay have shown that neonates receiving breast milk had better cognitive function through 7–8 years of age.[3] Developmental and immunological benefits of breast milk for the preterm neonate continue after the infant has been discharged; however, the composition of human milk may be inadequate to support optimal linear growth and bone mineralization after discharge. During the hospital stay, very low birth weight infants consuming human milk receive fortification with commercial powdered supplements designed to provide additional calories, protein, vitamins, calcium, and phosphorus. A small study recently showed that growth was improved and lactation unaffected when this same fortifier was provided for the first 3 months after discharge.[4] This study was the first on this topic and it is difficult to obtain human milk fortifier after discharge from the hospital. Therefore, further studies are necessary before this practice can be recommended routinely. However, pediatricians may use any type of commercial formula powder to increase the caloric density of breast milk for infants with inadequate weight gain after discharge. Preterm infants should receive multivitamins with iron while receiving human milk.

If a mother desires to breastfeed and the infant's weight gain is adequate, feeding directly from the breast should be promoted for its various other benefits (emotional, convenience, improved milk supply). Breastfeeding the premature infant can be complicated—from many physical and emotional aspects. Lactation support to establish strong breastfeeding patterns should be provided as needed, ideally prior to discharge. Ongoing support after discharge may be needed, specifically if the mother has questions or concerns or if she is transitioning to feeding directly from the breast. Once home, infants should be fed on-demand, every 1.5–3 hours. If the mother is bottle feeding and desires to use breast milk exclusively, she will need to pump as often as the baby feeds to maintain her supply. Many women pumping breast milk over long periods of time experience low milk supply and will need supplementary formula.

For formula-fed preterm infants, the choice of a formula may be difficult due to a large variety of choices on the market. Pediatricians should be aware that soy formulas may interfere with bone mineralization and the American Academy of Pediatrics (AAP) recommends that these formulas are not used in infants who weighed less than 1800 grams at birth.[5] Transitional post-discharge formulas specifically for preterm infants were developed in the early 1990s. These formulas provide more energy (22 kcal/oz), protein, calcium, phosphorus, iron, and vitamins than term formulas. The early studies of these formulas demonstrated improved growth over the first year, compared with standard formulas. Because of these initial studies, the AAP has supported the use of these formulas for the first 9 months. However, more recent studies have shown that the routine use of these formulas may not result in improved growth or bone mineralization in larger healthy preterm infants.[6] Additional studies are therefore needed before recommending these formulas on a widespread basis, but they remain useful for infants with growth problems after discharge or as a supplement for breastfed infants who may benefit from the additional calcium and phosphorus.

Iron is an important nutrient that is utilized in the function of synapses and the myelination of the brain. Iron deficiency anemia has been associated with abnormal brain development in animals and in full term newborns, leading to developmental delays that do not entirely reverse with correction of anemia.Lowbirthweight(<2500 grams) preterm infants have both low bodily iron stores at birth and rapid growth rates, resulting in increased iron needs.[7] Pediatricians should ensure that infants receive 2 mg/kg/day of iron until 1 year corrected age. Term and preterm formulas are designed to provide this amount when consumed at 120 cal/kg/day. Breastfed infants require supplemental iron (2 mg/kg/day). Some infants have increased requirements and need additional supplemental iron. Until infants are old enough to take iron fortified cereals and other foods, supplemental iron is most conveniently given using commercial preparations of multivitamins with iron oral drops. Preterm infants take the same preparations as full term infants that are available over the counter.

Hemoglobin should be checked regularly through the first 12–18 months.Smallerpreterminfants(<1500–1800 gram birth weight) will develop iron deficiency sooner than larger infants; these infants should be evaluated at about 4–6 months of age. When hemoglobin is less than 11 g/dl, supplemental iron (3–5 mg/kg/day) should be prescribed.

Feeding problems

Preterm infants are at increased risk for feeding problems, which may compromise weight gain or result in pulmonary aspiration. Typically these problems surface during the NICU stay, but problems also may present or worsen after discharge. Feeding problems are more likely to occur in premature infants and in infants with abnormal airways, chronic lung disease, severe gastroesophageal reflux, and neurological impairments. Infants with vocal cord paralysis (a complication of surgical ligation of the patent ductus arteriosus or prolonged mechanical ventilation), are at increased risk for aspiration. Poor dietary intakes, coughing, choking, cyanosis, or stridor during feedings and recurrent episodes of pneumonia are symptoms that should trigger evaluation by a speech language pathologist with expertise in infant feeding. Further evaluation, including a videofluoroscopic swallow study or referral to an otolaryngologist, may be indicated. Treatment may include alteration of feeding techniques, the use of special bottles or nipples, and thickening of feedings. If these measures do not ameliorate the problems, oral feedings must occasionally be decreased or stopped, necessitating nasogastric tube or gastrostomy tube feedings. This is usually on a temporary basis as further neurological maturation, therapy, and resolution of the underlying problems will allow the resumption of oral feedings.

Immunizations

The 2006 Report of the Committee on Infectious Disease (the Red Book)[8] includes new sections on immunization of preterm infants, affirming the long standing recommendation that routine vaccinations should be given at the same chronological age as full term infants. Preterm infants do not always mount the same response to immunizations as full term infants. However, responses are sufficient to prevent disease. The hepatitis B vaccine is generally given at discharge. Infants with prolonged hospitalizations should begin their immunizations during the NICU hospitalization at 2 months of age. Pediatricians may complete the series per their usual practices.

Preterm infants and infants with chronic lung disease are at particular risk for severe infection with respiratory syncytial virus (RSV). Preterm infants may present with the typical signs of respiratory distress or more non-specific signs such as lethargy, irritability, and poor feeding. Rapid detection assays are readily available to assist in diagnosis. Treatment is largely supportive and varies with the severity of infection; it ranges from close outpatient follow-up to intensive care management requiring mechanical ventilation or extracorporeal membrane oxygenation. Prevention is, therefore, ideal. Families with infants at risk for severe infection should be educated on the benefits of proper hand hygiene and avoidance of environmental pollutants and exposure to infected contacts.

Palivizumab, a mouse monoclonal antibody to RSV, has been shown to decrease the risk of hospitalization with severe RSV infection by 45%–55%.[8] Doses are given intramuscularly every 30 days beginning in November through March. Because palivizumab is expensive, the risk benefit ratio varies according to the gestational age, complicating factors during the infant's first season, and complicating factors during the second season (Table 1).

Post-marketing outcome data obtained from the Palivizumab Registry, 1998–2002, showed that 1.5%–2.9% of preterm infants given palivizumab prophylaxis were hospitalized.[9] Of these infants, 45%–58% had chronic lung disease and 19%–30% required admission to a pediatric intensive care unit. These data emphasize the continuing importance of hygiene and avoidance of irritants and infected contacts. An enhanced potency monoclonal antibody, which may improve the efficacy of the treatment, is currently under investigation.

Developmental care

Preterm infants at all gestational ages are at risk for developmental problems including vision problems, hearing loss, cerebral palsy, delayed development, and long term cognitive problems. [10,11] The incidence of developmental delays and use of Early Intervention services is lower with advancing gestational age, but all preterm infants are at increased risk compared with term infants (Figure 1).

No data are available for Illinois, but in Massachusetts, 16% of all Early Intervention services were used by moderately preterm and late preterm infants, with extremely preterm infants using 8% of these services.[11] Pediatricians therefore should be prepared to assess development and make Early Intervention referrals in preterm infants at all gestational ages.

Early diagnosis and therapy for neurosensory and developmental problems are associated with improved long term function.[12] Moderate and late preterm infants can be screened by pediatricians at well-child visits (see schedule in Table 2), using the office's preferred method of developmental screening, in addition to a neuromotor examination of motor milestones, muscle tone, reflexes, and postural responses.

Preterm infants weighing less than 1500 grams at birth should have formal developmental evaluations performed by specialists in psychology, occupational therapy or child development. Formal evaluations also should be recommended whenever screening results are concerning and when parents or pediatricians have concerns about development. In addition to monitoring development, some infants also require follow-up evaluations of vision or hearing (Table 2).

All level III NICUs in the state of Illinois must be affiliated with a multidisciplinary developmental follow-up clinic to monitor development of their high risk graduates. Pediatricians can utilize these clinics as resources for infants who need detailed developmental evaluation, even if the infant was not initially considered to be high risk and was not enrolled in the clinic. Formal developmental evaluations may also be obtained by referral to Early Intervention services or developmental pediatricians.

When delays are confirmed, infants should be referred for Early Intervention services or to an outpatient therapist. Language delays should prompt consideration of follow-up hearing testing if not recently performed.[12] Infants with hearing loss should be referred to an otolaryngologist. If cerebral palsy is suspected, infants should be referred to a physiatrist or neurologist. Developmental pediatricians are also helpful in assessing overall development, including behavioral and socio-emotional development. Finally, special programs are also available through Early Intervention for infants with vision or hearing losses.

Summary

Pediatricians care for a large number of preterm infants. Even when these infants are healthy, their needs for health supervision and preventive care are different from those of full term infants. Fortunately, good pediatric care and careful developmental surveillance can help to support growth and minimize health and developmental consequences of prematurity.

REFERENCES

[1.] Hamilton BE, Miniño AM, Martin JA, et al. Annual summary of vital statistics: 2005. Pediatrics 2007;119:345-360.

[2.] Hack M, Schluchter M, Cartar L, et al. Growth of very low birth weight infants to age 20 years. Pediatrics 2003;112:e30-38.

[3.] Lucas A, Morley R, Cole TJ, et al. Breast milk and subsequent intelligence quotient to infants born preterm. Lancet 1992;339:261-264.

[4.] O'Connor DL, Khan S, Weishuhn K, et al, Postdischarge Feeding Study Group. Growth and nutrient intakes of human milk-fed preterm infants provided with extra energy and nutrients after hospital discharge. Pediatrics 2008;121:766-776.

[5.] American Academy of Pediatrics, Committee on Nutrition. Soy Protein-based Formulas: Recommendations for use in infant feeding. Pediatrics 1998;101:148-153.

[6.] Henderson G, Fahey T, McGuire W. Nutrientenriched formula versus standard term formula for preterm infants following hospital discharge. Cochrane Database Syst Rev 2007; Issue 4.

[7.] Rao R, Georgieff MK. Neonatal iron nutrition. Seminars in Neonatology 2001;6:425-435.

[8.] American Academy of Pediatrics, Pickering LK, ed. Red Book: Report of the Committee of Infectious Diseases. 27th ed. Elk Grove Village (IL): AAP; 2006.

[9.] Romero JR. Palivizumab prophylaxis of respiratory syncytial virus disease from 1998 to 2002: Results from four years of palivizumab usage. Ped Infectious Disease J 2003;22:S46-54.

[10.] Wang CJ, McGlynn EA, Brook RH, et al. Quality-of-care indicators for the neurodevelopmental follow-up of very low birth weight children: Results of an expert panel process. Pediatrics 2006;117;2080-2092.

[11.] Clements KM, Barfield WD, Ayadi MF, Wilber N. Preterm birth-associated cost of Early Intervention services: An analysis by gestational age. Pediatrics 2007;119:e866-874.

[12.] Joint Committee on Infant Hearing. Year 2007 position statement: Principles and guidelines for early hearing detection and intervention programs. Pediatrics 2007;120;898-921.