The rate of preterm births has gradually declined since its peak in 2006.1,2 With major advances in life-sustaining neonatal care, the population of preterm infants born near the limits of viability and surviving to discharge will continue to rise.3 Preterm infants have a plethora of health problems unique to them. Transitioning from months-long intensive care to the ambulatory environment can be daunting for most families. The general pediatrician plays an important role in continuing direct medical care and coordinating care with subspecialists following discharge from the neonatal intensive care unit (NICU). In this article, the authors touch upon the pertinent health problems and continuing care of the preterm infant during pediatric office visits. The focus will primarily be on very low birth weight (VLBW) infants (≤1,500 g).
A number of fetal-infant growth charts are available for assessing postnatal growth in preterm infants. The most commonly used in NICUs is the Fenton growth chart. The Fenton growth chart is based on a meta-analysis of large population-based studies.4 It uses weight, length, and head circumference parameters starting at 22 weeks of gestation up to 10 weeks post-term (ie, 50 weeks post-menstrual age). It thus provides an overlap between fetal and infant growth charts between 40 weeks (full term) and 50 weeks post-menstrual age. Most recently, the Fenton growth chart was revised to smooth the disjuncture at this point of overlap and to provide sex-specific growth charts.5,6 Between 40 and 50 weeks post-menstrual age, the practitioner can use either the Fenton or the World Health Organization (WHO) 2006 growth charts. Beyond 50 weeks post-menstrual age, the practitioner must use the WHO 2006 growth chart for children younger than 2 years and the US Centers for Disease Control and Prevention (CDC) 2000 growth chart for ages 2 to 20 years. The corrected age is used when evaluating growth parameters with the WHO and CDC charts up to 3 years of chronological age.7 The corrected age is derived by subtracting the number of weeks/months the infant was born premature (using 40 weeks as full term) from the chronological age.8 Preterm infants demonstrate catch-up growth during the first 3 years of life. Catch-up growth is defined as accelerated growth velocity following a period of slow growth.9 Catch-up growth can continue into childhood and adolescence.10
Soon after birth, preterm neonates lose weight, which is then regained within 2 to 3 weeks.11 To achieve adequate catch-up growth, an increment in weight, length, and head circumference of approximately 15 to 20 g/kg/day, 0.9 cm/week, and 0.9 cm/week, respectively, is required.11,12 Despite optimizing nutrition, most infants discharged from the NICU are below the 10th percentile for weight due to gut immaturity and other complicating medical conditions such as sepsis, necrotizing enterocolitis, and chronic lung disease.11 There are data that suggest too-rapid catch-up growth puts preterm infants at risk for obesity and metabolic syndrome.13,14 It is key to ensure that the preterm infant is gaining weight, length, and head circumference to catch up with their term counterparts by age 3 years. After discharge, these parameters should be monitored more frequently than is done for term infants to ensure that the preterm infant is not lagging behind.
Energy requirements to sustain growth are higher in preterm infants compared with term infants. Greater caloric requirements are necessary to achieve growth in infants with comorbidities such as bronchopulmonary dysplasia secondary to increased energy expenditure.15 The energy requirement for most preterm infants to continue adequate intra-uterine growth (∼15 g/kg/day) is 100 to 130 kcal/kg/day.7,16 Infants who are small for gestational age may require higher caloric intake than infants who are normal for gestational age.16 Preterm infants have a high need for protein, calcium, phosphorous, vitamin D, and iron that needs to be matched in their diet.
When available, human milk should be given priority for feeding preterm infants because it has been associated with improved long-term neurodevelopmental outcomes and fewer rehospitalizations.17,18 Unfortified human milk does not provide sufficient calories and nutrients for preterm infants.7 Breast milk fortified with liquid fortifiers and preterm formulas contain adequate quantities of nutrients such that the preterm infant has weight gain, body composition, and bone mineralization similar to full-term infants.19 Prior to discharge, infants are transitioned to unfortified human milk with or without supplementation with preterm transitional formulas (22 kcal/oz) or just preterm (24 to 30 kcal/oz) or term formula (20 kcal/oz) depending on corrected age, growth velocity, and maternal milk supply.20
Controversy exists regarding the type and duration of diet in preterm infants post-discharge. A number of studies have shown better weight gain, lean mass body composition, and bone mineralization when preterm infants were fed preterm formulas up to 6 months to as long as 12 months of corrected age.21,22 No added benefit of this was noted on neurodevelopment.23,24 Preterm infants may be transitioned off of highly enriched preterm formula and started on transitional formula at approximately 2,000 g if they are not fluid restricted. Preterm formulas may be used up to 3,000 g.25
Iron (2 mg/kg/day) should be given as a supplement to preterm infants receiving unfortified human milk up until age 12 months,7 but supplementation with multivitamins is controversial. However, vitamin D supplementation (200 to 400 IU/day) is essential when unfortified human milk is the sole source of nutrition because mothers may be deficient in vitamin D.25 Vitamin D is important in addition to calcium and phosphorous supplementation to prevent osteopenia that often occurs in preterm infants. Alkaline phosphatase activity should be monitored for 2 to 4 weeks after discharge, and levels higher than 800 to 1,000 IU/L require close follow-up and additional nutrient supplementation.25
Preterm infants are at risk for delayed development and long-term cognitive problems. The risk rises with decreasing gestational age. Routine surveillance to monitor gross and fine motor, language, problem-solving, and personal-social skills of the growing preterm infant is essential to detect delays and begin intervention. Statewide early intervention programs that are state and federally funded through the Individuals with Disabilities Education Act exist to provide evaluations and services for infants at risk for developmental delays. VLBW infants should be enrolled in the program based on the state qualifying criteria. Development should be assessed using the Ages and Stages Questionnaire (ASQ) or the Denver Developmental Screening Test and the corrected age of the preterm infant up to 2 years.26,27 It is prudent to remember that these diagnostic tools are not always effective in identifying developmental delays in preterm infants.28 Hence, it is important for all VLBW infants to be followed up in a specialized developmental clinic where trained personnel can administer the Bayley Infant and Toddler Scales of Development.
Routine preventive care, as offered to full-term infants, should be provided to preterm infants with some additions.29
All preterm infants are at risk for hearing deficiencies, especially those on assisted ventilation for prolonged periods and those receiving ototoxic medications such as gentamicin/tobramycin or loop diuretics. All preterm infants should have their hearing tested prior to discharge. Following discharge, infants should undergo periodic objective screening and assessment of risk factors for hearing loss. Objective screening could be either an oto-acoustic emissions test or an automated auditory brainstem response (ABR). Risk factors to be assessed are outlined in Table 1. If infants fail the hearing test, they should be referred to an audiologist for a more thorough evaluation that may include a sedated ABR. Infants with risk factors should have at least one audiology evaluation by age 24 to 30 months, even if the newborn hearing screen was normal.30
Risk Factors Associated with Hearing Loss
Retinopathy of prematurity is a disease of immature retina that leads to blindness in preterm infants. All preterm infants ≤ 30 weeks gestational age or ≤ 1,500 g are screened at 31 weeks postmenstrual age or 4 weeks chronological age, whichever comes later. Infants older than 30 weeks gestational age or with a birth weight between 1500 and 2000 g with an unstable course and requiring cardiorespiratory support should be screened at 4 weeks chronological age. Pediatricians should be aware that these infants may also develop other unrelated eye problems, such as strabismus or refractive errors, and that these need to be investigated if found on physical examination.31
Preterm infants should be immunized according to their chronologic age, just like term infants, as long as the infants are clinically stable.32 The immune response generated is not as robust in VLBW infants, but it is sufficient to prevent disease. Infants born weighing < 2,000 g should start their hepatitis B vaccine series at 1 month of chronologic age or at discharge if being discharged at younger than 1 month of age. Preterm infants with prolonged hospitalization should receive immunizations per their chronologic age except for live vaccines. Infants being discharged from the NICU between 6 weeks and 14 weeks and 6 days of life should receive the first dose of the rotavirus vaccine. After discharge, the vaccines should be administered in the pediatrician’s office per the recommended schedules for term infants.32
Preterm infants, especially those with chronic lung disease, are susceptible to respiratory syncytial virus (RSV) infection. In this population, RSV infection can be fatal. To protect these infants, palivizumab, a humanized mouse monoclonal antibody, is administered monthly during the RSV season. Table 2 shows the most updated guidelines regarding vaccination with palivizumab. Pediatricians should ensure their patients’ compliance with this monthly vaccination and advise families on good hand hygiene practices.34 In addition to RSV, influenza and pertussis are other causes of morbidity and mortality. Pediatricians should encourage family members, including mothers, to be vaccinated against influenza and pertussis to protect infants.
Guidelines for Administration of Palivizumab
Abnormal Head Shapes
Preterm infants are at risk for developing abnormal head shapes such as dolicocephaly (elongated head along the sagittal suture), deformational plagiocephaly (oblique flattened head), or brachycephaly (flattened occiput). These occur as a result of compression of soft skull bones because of positional limitations, certain nursing care practices (such as side lying or supine or prone positioning), and medical management. Older infants with head deformities receive helmet therapy. A recent randomized, controlled trial showed no added benefit of helmet therapy.35
Multidisciplinary and Family Centered Care
Preterm infants have multiple comorbidities, such as bronchopulmonary dysplasia, intraventricular hemorrhage, short gut from necrotizing enterocolitis, and retinopathy of prematurity, that require numerous types of subspecialty care. Pediatricians must identify these comorbidities and ensure that the infant is receiving the follow-up subspecialty care that is needed. It is not uncommon for families of preterm infants to get overwhelmed with the complexity of care for their preterm babies. Primary care physicians should be able to recognize this and provide support services when needed. Some parents can become overly protective of their infant, leading to family conflicts and neglecting of other children. It is the physician’s job to provide reassurance to the family and maintain a thorough follow-up with the infant.
Pediatricians already care for a large number of preterm infants, and this number will continue to rise. Good growth and developmental surveillance and practice of preventive care can help families feel comfortable caring for their babies while preventing frequent rehospitalizations.
- Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Wilson EC, Mathews TJ. Births: final data for 2010. Natl Vital Stat Rep. 2012;61(1):1–71.
- March of Dimes. 2013 Premature Birth Report Card. http://www.marchofdimes.com/glue/files/premature-birth-report-card-united-states.pdf. Accessed August 6, 2014.
- Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ. 2012;345:e7976. doi:10.1136/bmj.e7976 [CrossRef]
- Fenton TR. A new growth chart for preterm babies: Babson and Benda’s chart updated with recent data and a new format. BMC Pediatr. 2003;3:13. doi:10.1186/1471-2431-3-13 [CrossRef]
- Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013;13:59. doi:10.1186/1471-2431-13-59 [CrossRef]
- Fenton TR, Nasser R, Eliasziw M, Kim JH, Bilan D, Sauve R. Validating the weight gain of preterm infants between the reference growth curve of the fetus and the term infant. BMC Pediatr. 2013;13(1):92. doi:10.1186/1471-2431-13-92 [CrossRef]
- American Academy of Pediatrics Committee on Nutrition. Assessment of Nutritional Status. In: Kleinman RE, Greer FR, eds. Pediatric Nutrition. 7th ed. Elk Grove Village, IL; American Academy of Pediatrics;2014:617.
- Engle WAAmerican Academy of Pediatrics Committee on Fetus and Newborn. Age terminology during the perinatal period. Pediatrics. 2004;114(5):1362–1364. doi:10.1542/peds.2004-1915 [CrossRef]
- Rugolo LM. Growth and developmental outcomes of the extremely preterm infant [in Portuguese]. J Pediatr. 2005;81(Suppl 1):S101–S110. doi:10.2223/JPED.1309 [CrossRef]
- Euser AM, de Wit CC, Finken MJ, Rijken M, Wit JM. Growth of preterm born children. Horm Res. 2008;70(6):319–328. doi:10.1159/000161862 [CrossRef]
- Ehrenkranz RA, Younes N, Lemons JA, et al. Longitudinal growth of hospitalized very low birth weight infants. Pediatrics. 1999;104(2 Pt 1):280–289. doi:10.1542/peds.104.2.280 [CrossRef]
- Griffin IJ. Nutritional assessment in preterm infants. Nestle Nutr Workshop Ser Pediatr Program. 2007;59:177–188; discussion 188–192.
- Jain V, Singhal A. Catch up growth in low birth weight infants: striking a healthy balance. Rev Endocr Metab Disord. 2012;13(2):141–147. doi:10.1007/s11154-012-9216-6 [CrossRef]
- Odegaard AO, Choh AC, Nahhas RW, Towne B, Czerwinski SA, Demerath EW. Systematic examination of infant size and growth metrics as risk factors for overweight in young adulthood. PLoS One. 2013;8(6):e66994. doi:10.1371/journal.pone.0066994 [CrossRef]
- Weinstein MR, Oh W. Oxygen consumption in infants with bronchopulmonary dysplasia. J Pediatr. 1981;99(6):958–961. doi:10.1016/S0022-3476(81)80032-7 [CrossRef]
- van Goudoever JB, Sulkers EJ, Lafeber HN, Sauer PJ. Short-term growth and substrate use in very-low-birth-weight infants fed formulas with different energy contents. Am J Clin Nutr. 2000;71(3):816–821.
- Vohr BR, Poindexter BB, Dusick AM, et al. Persistent beneficial effects of breast milk ingested in the neonatal intensive care unit on outcomes of extremely low birth weight infants at 30 months of age. Pediatrics. 2007;120(4):e953–e959. doi:10.1542/peds.2006-3227 [CrossRef]
- Vohr BR, Poindexter BB, Dusick AM, et al. Beneficial effects of breast milk in the neonatal intensive care unit on the developmental outcome of extremely low birth weight infants at 18 months of age. Pediatrics. 2006;118(1):e115–e123. doi:10.1542/peds.2005-2382 [CrossRef]
- Ziegler EE, O’Donnell AM, Nelson SE, Fomon SJ. Body composition of the reference fetus. Growth. 1976;40(4):329–341.
- Martinez JA, Ballew MP. Infant formulas. Pediatr Rev. 2011;32(5):179–189; quiz 189. doi:10.1542/pir.32-5-179 [CrossRef]
- Carver JD, Wu PY, Hall RT, et al. Growth of preterm infants fed nutrient-enriched or term formula after hospital discharge. Pediatrics. 2001;107(4):683–689. doi:10.1542/peds.107.4.683 [CrossRef]
- Chan GM. Growth and bone mineral status of discharged very low birth weight infants fed different formulas or human milk. J Pediatr. 1993;123(3):439–443. doi:10.1016/S0022-3476(05)81754-8 [CrossRef]
- Cooke RJ, Embleton ND, Griffin IJ, Wells JC, McCormick KP. Feeding preterm infants after hospital discharge: growth and development at 18 months of age. Pediatr Res. 2001;49(5):719–722. doi:10.1203/00006450-200105000-00018 [CrossRef]
- Henderson G, Fahey T, McGuire W. Calorie and protein-enriched formula versus standard term formula for improving growth and development in preterm or low birth weight infants following hospital discharge. Cochrane Database Syst Rev. 2005;(2):CD004696.
- Abrams SACommittee on Nutrition. Calcium and vitamin D requirements of enterally fed preterm infants. Pediatrics. 2013;131(5):e1676–e1683. doi:10.1542/peds.2013-0420 [CrossRef]
- Schonhaut L, Armijo I, Schonstedt M, Alvarez J, Cordero M. Validity of the ages and stages questionnaires in term and preterm infants. Pediatrics. 2013;131(5):e1468–e1474. doi:10.1542/peds.2012-3313 [CrossRef]
- Elliman AM, Bryan EM, Elliman AD, Palmer P, Dubowitz L. Denver developmental screening test and preterm infants. Arch Dis Child. 1985;60(1):20–24. doi:10.1136/adc.60.1.20 [CrossRef]
- Woodward BJ, Papile LA, Lowe JR, et al. Use of the Ages and Stages Questionnaire and Bayley Scales of Infant Development-II in neurodevelopmental follow-up of extremely low birth weight infants. J Perinatol. 2011;31(10):641–646. doi:10.1038/jp.2011.1 [CrossRef]
- Recommendations for Preventive Pediatric Health Care. Bright Future/American Academy of Pediatrics. http://www.aap.org/en-us/professional-resources/practice-support/Periodicity/Periodicity%20Schedule_FINAL.pdf. Accessed August 13, 2014.
- Harlor AD Jr, Bower CCommittee on Practice and Ambulatory Medicine; Section on Otolaryngology-Head and Neck Surgery. Hearing assessment in infants and children: recommendations beyond neonatal screening. Pediatrics. 2009;124(4):1252–1263. doi:10.1542/peds.2009-1997 [CrossRef]
- Fierson WMAmerican Academy of Pediatrics Section on OphthalmologyAmerican Academy of OphthalmologyAmerican Association for Pediatric Ophthalmology and StrabismusAmerican Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013;131(1):189–195. doi:10.1542/peds.2012-2996 [CrossRef]
- American Academy of Pediatrics. Red Book: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
- Lieberthal AS, Meissner HC. AAP updates guidance on use of palivizumab for RSV prophylaxis. AAP News. 2014;35(8):1.
- Committee On Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among infants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014;134(2):e620–e638. doi:10.1542/peds.2014-1666 [CrossRef]
- van Wijk RM, van Vlimmeren LA, Groothuis-Oudshoorn CG, Van der Ploeg CP, Ijzerman MJ, Boere-Boonekamp MM. Helmet therapy in infants with positional skull deformation: randomised controlled trial. BMJ. 2014;348:g2741. doi:10.1136/bmj.g2741 [CrossRef]
Risk Factors Associated with Hearing Loss
Caregiver concern regarding hearing, speech, language, or developmental delay
Family history of permanent childhood hearing loss
Neonatal intensive care for longer than 5 days or any of the following regardless of length of stay: extracorporeal membrane oxygenation, assisted ventilation, exposure to ototoxic medications (gentamicin and tobramycin) or loop diuretics (furosemide), and hyperbilirubinemia that requires exchange transfusion
In utero infections such as cytomegalovirus, herpes, rubella, syphilis, and toxoplasmosis
Craniofacial anomalies, including those that involve the pinna, ear canal, ear tags, ear pits, and temporal bone anomalies
Physical findings, such as white forelock, that are associated with a syndrome known to include a sensorineural or permanent conductive hearing loss
Syndromes associated with hearing loss or progressive or late-onset hearing loss, such as neurofibromatosis, osteopetrosis, and Usher syndrome; other frequently identified syndromes include Waardenburg, Alport, Pendred, and Jervell and Lange-Nielson
Neurodegenerative disorders, such as Hunter syndrome, or sensory motor neuropathies, such as Friedreich ataxia and Charcot-Marie-Tooth syndrome
Culture-positive postnatal infections associated with sensorineural hearing loss, including confirmed bacterial and viral (especially herpes viruses and varicella) meningitis
Head trauma, especially basal skull/temporal bone fracture that requires hospitalization
Recurrent or persistent otitis media for at least 3 months
Guidelines for Administration of Palivizumab
|Infants eligible for palivizumab in the 1st year of life
|All infants < 29 weeks gestational age at birth
|Infants < 32 weeks gestational age with chronic lung disease of prematurity, defined as > 21% oxygen for at least 28 days after birth
|Infant, with hemodynamically significant cardiac disease
|Infants eligible for palivizumab until 2nd year of life
|Infants on supplemental oxygen for at least first 28 days of life and continuing to require medical intervention such as supplemental oxygen, steroid, and/or diuretic therapy
|Infants in whom palivizumab should be considered
|Infants with pulmonary abnormality
|Infants with neuromuscular disability with inability to clear secretions in lower airways
|Children < 2 years of age who will be severely immunocompromised during respiratory syncytial virus season
|Infants not eligible for palivizumab
|Infants ≥ 29 weeks and otherwise healthy
|Any infant who experiences breakthrough respiratory syncytial virus infection despite vaccination