Short- and Long-term Challenges of Prematurity

Challenges of Prematurity

The preterm birth rate in the US has increased by more than 20% since 1990. Currently, 1 in 8 births are premature. Premature birth is now the most common infant health problem in the country.1 The increasing number of infants born prematurely requires that pediatricians be as current as possible on the immediate health challenges for the premature infant as well as potential long-term issues.

In the first weeks of life, prematurity can pose significant risks to the infant’s health. Although risks are lower the later the infant is born and the higher their birthweight, even late preterm infants have a greater risk of acute and ongoing issues relating to respiratory distress syndrome, feeding and digestion, brain development, jaundice and temperature instability. Attention in the NICU is focused on supporting and enhancing vital organ development, with some of the more intense interventions being carried out in support of lung function, brain function including breathing control, and gastrointestinal immaturities. At the other end of the technology scale, simple measures including kangaroo care, enteral feeding with breastmilk, and vigilant infection control measures can significantly reduce morbidity and mortality for preterm infants.2

While physical manifestations of prematurity are well understood, some complications, particularly neurologic, are not fully apparent until the child is older, usually at school age.

Potential complications of prematurity

• Respiratory distress syndrome
• Bronchopulmonary dysplasia

• Patent ductus arteriosus

• Feeding difficulties
• Absorptive, digestive difficulties
• Necrotizing enterocolitis

• Apnea of prematurity
• Retinopathy of prematurity
• Cerebral palsy
• Developmental disabilities

Respiratory Distress Syndrome and Bronchopulmonary Dysplasia – RDS is one of the most common lung disorders in premature infants, affecting about 10%. Most infants who develop RDS show signs of breathing difficulty at birth or within the following few hours. The cause is largely the result of surfactant deficiency and lung immaturity in both structure and function. Many infants born with serious RDS go on to develop BPD. BPD usually develops within 1-2 weeks after birth; injury to small airways and microvascular development is implicated, the combined result of lung immaturity plus prolonged oxygen and mechanical ventilation. Infants with BPD are at risk for repeated pulmonary infections.3,4

Patent ductus arteriosus (PDA) – In the premature infant with PDA, the ductus arteriosus does not close within the first 12-24 hours after birth as it normally does. PDA can complicate respiratory problems, as well as affect blood pressure. If the ductus arteriosus does not close spontaneously or respond to treatment with indomethacin, ligation surgery is required to close it.3,4

Gastrointestinal immaturities – The “mechanical” immaturities of the premature infant’s GI tract affect feeding tolerance, digestion, upper and lower GI motility and absorption. GERD and necrotizing enterocolitis are serious results of GI immaturity.3,4

GERD – Both premature and full-term infants experience gastroesophageal reflux (GER), which is distinguished from GERD by the number and severity of reflux episodes and complications including strictures, malnutrition, respiratory disorders, and bleeding. For premature infants, an incompetent lower esophageal sphincter combined with delayed gastric emptying can lead to GERD. An indirect sign, especially in premature babies, is apnea associated with bradycardia. 

Necrotizing enterocolitis (NEC) – occurs in about 10% of premature infants weighing less than 1,500 grams. The pathogenesis of NEC is not completely established, but evidence suggests that it is a function of multiple causes including the presence of abnormal bacterial flora, intestinal ischemia, and intestinal mucosal immaturity/dysfunction. NEC is rare in infants who have not received feedings. When feedings are started and food moves into a weakened area of the intestinal tract, bacteria from the food can damage the intestinal tissues. Severe tissue damage can cause a perforation to develop, leading to infection in the abdomen. Initial signs of NEC include feeding intolerance, delayed gastric emptying and abdominal distension and tenderness.3,4

Apnea of Prematurity (AOP) –Apnea is the most common problem of ventilatory control in the premature infant, defined by a cessation of breathing for 20 seconds, or for a shorter period of time if accompanied by bradycardia, cyanosis, or pallor. The incidence and severity of apnea in premature infants are inversely related to gestational age. Approximately 50% of VLBW infants require either pharmacologic intervention or ventilatory support. The peak incidence occurs between 5 and 7 days postnatal age. AOP usually resolves at 34 to 36 weeks postconceptual age.3,4

Retinopathy of prematurity (ROP) – ROP occurs mainly in ELBW infants. Premature birth interrupts development of the retinal vasculature; prolonged exposure to supplemental oxygen required for the premature infant’s lung function further exacerbates the condition. ROP often regresses or heals, but it can lead to severe visual impairment or blindness; myopia, amblyopia, or strabismus may occur.3,4

Cerebral palsy (CP) – CP is an umbrella term describing non-progressive brain lesions that occur during early development, with resulting disorders varying by the week of gestation when the injury occurred. Preterm birth is only one of many risk factors for CP. The motor disorders of cerebral palsy may be accompanied by other disturbances including cognition, communication, perception, behavior and a seizure disorder.3,4

Developmental disabilities – As increasing numbers of VLBW and ELBW survive the early physical challenges of prematurity, attention is focusing on understanding longer-term implications for the child’s developmental progress. Developmental disabilities resulting from premature birth range from cognitive and academic abilities, fine and gross motor skills, vision and hearing, and attention and behavioral deficits.

Long-term developmental outcomes: Where are we today?
It is only in the longer term that certain developmental outcomes relating to prematurity become apparent. Prior to the development of exogenous surfactant, which began regular use in the US in the early 1990s, studies reported serious neurological outcomes for VLBW infants, including higher rates of cerebral palsy, visual impairment, poor developmental outcome and behavior problems. The question remains of whether the risk of neurologic, cognitive and educational outcomes is improved with surfactant therapy and other advancements in NICU procedures, and if so, whether improved outcomes are still apparent in the longer term.

Compared with full-term infants, premature infants have been found to demonstrate poorer scores relating to behavioral organization, attention to sensory stimuli, and self-regulation. It is thought that these early deficits are related to later deficits in children’s attention regulation and executive functioning.2

Numerous follow-up studies have been conducted on premature infants to assess later evidence of developmental delays:

  • The EPICure Study followed a group of infants born at 25 or fewer weeks’ gestation in 1995. More than 60% received steroid treatment and 84% received surfactant. At 30 months of age, 24% of the survivors had severe disabilities in neuromotor, cognitive, hearing and vision domains, with cognitive impairment most common. These children were evaluated again at 6 years of age. Of the children observed to have severe disability at 30 months of age, 86% still had moderate-to-severe disability at age 6. However, children with less severe disabilities at 30 months were developmentally comparable at age 6 to those without disability at 30 months.5
  • A study comparing rates of survival and neurodevelopmental impairment at corrected age 20 months in two groups of infants, one group born before the introduction of surfactant therapy vs. one group born after, found that overall survival rates increased from 49% pre-surfactant to 67% with surfactant therapy, but the rates of survival both without impairment and with impairment increased.6
  • A 12-year study completed in 1997 evaluated a group of premature infants born in pre-surfactant, transitional, and surfactant eras, and found that the rate of neurologic impairment remained constant at approximately 11%.7
  • A 15-year follow-up study of children born at less than 29 weeks’ gestation who received surfactant therapy found that a significant minority required intensive special education services through secondary school age.7
  • Presence of disabilities in more than one developmental domain predicts a more serious outcome for preterm infants. A follow-up study of children born <30 weeks’ gestation evaluated neurological, motor, cognitive and behavioral effects. 39% were observed to have a normal developmental outcome, 17% had a single disability, and 44% had multiple disabilities. Multiple disabilities were associated with lower birthweight, BPD and continuing neurodevelopmental difficulties as observed at age 2.8
  • VLBW infants have a higher likelihood of having behavioral problems, delays in motor development, and difficulties in school, all issues that lie within the domain of executive functioning. The fact that preterm children show more generalized learning problems rather than specific learning disabilities (e.g., only a reading problem) supports the theory that preterm children’s learning difficulties are caused by a global processing deficit rather than difficulties with particular skills.2
  • A study of 10-year-old VLBW preterm children showed that 20% suffered from attention deficits compared with 8% of full-term children.2


Implications for care: Life after the NICU
Because the long-term effects of some complications of prematurity are reasonably well anticipated, regular follow-up visits provide an opportunity to identify these problems if and as they develop. It is important to have a specified plan in place at discharge for the infant’s continuing healthcare and parenting support. 

Medical problems originating in the initial weeks of life may require care for months or years. Other conditions may be identified later in infancy or in childhood, therefore continual attentiveness to early signs is valuable. 

Each follow-up appointment should include review of developmental milestones so that early intervention can be initiated if a developmental delay is identified or suspected. As with any developmental problem, early intervention and therapy is a key strategy.

There are a number of common issues to be watchful for in follow-up appointments:

Growth and nutrition: During the first two years, growth of the premature infant follows their age corrected for prematurity using a special premature growth chart. After the age of two, the child’s progress may be followed using the standard growth chart. 

Nutrient reserves in premature infants tend to be low at discharge, therefore nutritional status should be assessed at each follow-up visit. Ongoing supplements are recommended for preterm infants who are breastfed to meet additional nutritional needs. Formula-fed infants who are gaining weight well can transition from a preterm formula to a regular routine formula, while those who require additional calories to meet weight goals may be fed a discharge formula until they meet weight goals and can be transitioned to a routine formula.9

Anemia: Anemia can be managed with iron supplementation. Supplemental iron should be given to preterm infants for 12 to 15 months.10,11

Gastroesophageal reflux: Gastroesophageal reflux is common in premature infants and usually presents as spitting up after feeding. Severe GER can cause feeding difficulties, irritability, poor weight gain and respiratory problems. Keeping the infant in a semi-upright position after feeding may improve symptoms. GER tends to resolve as the infant’s GI system matures.10,11

Respiratory: Premature infants with a history of severe neonatal respiratory distress such as bronchopulmonary dysplasia may need more frequent follow-up to be vigilant for wheezing or pulmonary infections. Infants are likely to have persistent respiratory issues up to about one year of age. For example, hospitalization for a cold that causes wheezing and difficulty breathing is not uncommon for infants who have had early respiratory difficulties. Respiratory difficulties tend to become less frequent after the first year; group daycare therefore may not be advisable in the first year. Infants with bronchopulmonary dysplasia can experience poor lung function until adolescence, when lung function typically becomes normal.10,11 

Apnea: Apnea of prematurity tends to improve as the infant matures, usually resolving by about 42 to 44 weeks adjusted age.10,11

Vision: Visual problems, such as those associated with retinopathy of prematurity, should be followed regularly after discharge, with regular vision exams. Premature infants are also at increased risk for issues with eye muscle strength (e.g., strabismus) and may require glasses for correction.10,11

Hearing: All preterm infants should have their hearing tested at least once during their first year to make sure they do not have hearing problems. Early identification of hearing impairment is critical for the child’s language development.10,11

Immune system: Vaccination is a critical part of preventive care for the preterm infant and should be given according to chronologic (not adjusted) age. Influenza vaccine is recommended infants over six months of age with chronic medical problems, particularly pulmonary disease. Vaccination against influenza should be considered for members of the family of the preterm infants.10,11

Developmental issues: Ongoing follow-up physical examinations and monitoring of developmental milestones help identify cerebral palsy or other developmental problems as early as possible to enable an early start to appropriate interventions.10,11

Parent education and support
Parent counseling is an important part of managing the needs of the premature infant. In the hospital, a team of specialists supports the premature infant, but once the infant is strong enough to be sent home, parents may be anxious about handling their child’s needs on their own. Most NICUs have developmental follow-up programs, and the parents should be encouraged to participate in these programs.

A recent study confirms that care of VLBW children has a significant and lasting impact on the family, particularly when chronic health issues are present. Mothers of 8 year old VLBW children with chronic lung problems were more likely to describe their child as having greater physical limitations and being more demanding and hyperactive or less adaptable than were mothers of VLBW children without lung problems or full-term children. While mothers do adapt to the medical, financial, and caregiver demands over time, with stress lower at age 8 than at age 2, the stress is nonetheless significant.12

Ongoing care and follow-up appointments – while crucial to monitoring and supporting the child’s long-term growth and development – may become a burden to parents. Parents may need support to remember that these follow-up visits provide the facts they need to help their child live to the best of their abilities. In the case of the premature child who is developing well and without issues, parents may need help to recognize that the frail stage has passed. As the child grows, they will encounter the routine illnesses and issues such as immunizations that concern any child – and parents may require support to realize that these are normal and do not represent a deterioration or regression of their child’s health status.

It is important to put research findings into perspective: while a proportion of premature infants do demonstrate poorer outcomes in the long term, the majority of VLBW and a significant percentage of ELBW children function within normal limits as they grow and mature.

Since the technology and procedures in the NICU are constantly evolving, as are approaches to interventions and therapies, long-term follow-up studies are key to understanding what lies in the future of the premature infant.


  1. Centers for Disease Control, National Center for Health Statistics.
  2. Kessenich M. Developmental outcomes of premature, low birth weight and medically fragile infants.
  3. NICU-WEB.
  4. Neonatology on the Web. 
  5. Marlow N et al. for the EPICure Study Group. Neurologic and Developmental Disability at Six Years of Age after Extremely Preterm Birth. NEJM 2005;352(1):9–19.
  6. Wilson-Costello D et al. Improved survival rates with increased neurodevelopmental disability for extremely low birth weight infants in the 1990s. Pediatrics 2005;115:997–1003. 
  7. D’Angio CT et al. Longitudinal, 15-Year Follow-up of Children Born at Less than 29 Weeks’ Gestation After Introduction of surfactant Therapy Into a Region: Neurologic, Cognitive, and Educational Outcomes. Pediatrics 2002;110:1094–102. 
  8. van Baar AL et al. Very Preterm Birth is Associated with Disabilities in Multiple Developmetnal Domains. Journal of Pediatric Psychology 2005;30(3):247–55. 
  9. Trachtenbarg DE, Golemon TB. Care of the Premature Infant: Part I. Monitoring Growth and Development. American Family Physician 1998;57(9): 2123–30. 
  10. LaHood A, Bryant CA. Outpatient care of the premature infant. American Family Physician 2007;76(8):1159–64.
  11. Trachtenbarg DE, Golemon TB. Office Care of the Premature Infant: Part II. Common Medical and Surgical Problems. American Family Physician 1998;57(10): 2383–90. 
  12. Singer LT et al. Parenting Very Low Birth Weight Children at School Age: Maternal Stress and Coping. J Pediatrics 2007;151(5):463–9.
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