I. INTRODUCTION. Of the over 4 million children born each year in this country, 2% (88,000) are born very preterm, which is defined as <32 weeks’ gestational age (GA). Advances in obstetric and neonatal care have resulted in increased survival of these infants. The ramifications of this improvement are vast because these infants are at increased risk for long-term complication including neurodevelopmental sequelae, such as cognitive delay, cerebral palsy, fine and gross motor coordination problems, learning disabilities, visual and hearing problems, and medical problems, such as respiratory, cardiovascular, and growth issues. The more preterm an infant, the greater the risk of such difficulties. It is thus critical that these children have appropriate long-term follow-up care which includes provision of close monitoring of the most common problems of the preterm infant.

A. Respiratory issues (see Chapter 34). Very preterm infants are at high risk for respiratory ailments, especially during the first year. Many present to primary care practitioners and specialists with chronic wheezing and
recurrent respiratory tract infections. Children of the lowest gestations and birth weights suffer the greatest burden of respiratory illness. Very low birth weight (VLBW; birth weight <1,500 g) infants are 4 times more likely to be rehospitalized during the first year than are higher birth weight infants; up to 60% are rehospitalized at least once by the time they reach school age. The increased risk of hospitalization persists into early school age; 7% of VLBW children are hospitalized in a given year, compared with 2% of higher birth weight children. In a recent study of extremely premature infants, 57% of infants born between 23 and 25 weeks’ gestation, and 49% of those born between 26 and 28 weeks’ gestation required rehospitalization in the first 18 months of life. Admissions during the first year of life are most commonly for complications of respiratory infections among very preterm and VLBW infants.

Lung development continues during the postnatal period, and exposure to volutrauma and barotrauma along with hyperoxia may impede this process. This can damage lung tissue and decrease pulmonary blood flow. The resultant lung disease can extend into adulthood.

Approximately 23% of VLBW infants and 40% of extremely low birth weight (ELBW; birth weight <1,000 g) infants develop bronchopulmonary dysplasia (BPD) (defined as O₂ dependence beyond 28 days with the severity assessed at 36 weeks’ postmenstrual age [PMA]). Very preterm infants with BPD are most likely to suffer respiratory ailments in the short and long term and should be monitored for related morbidities, including acute respiratory exacerbations, upper and lower respiratory infections, pulmonary hypertension, cor pulmonale, growth failure, and developmental delay. Infants with severe BPD may require treatment with tracheostomy and long-term ventilator support. More commonly, infants with significant BPD may be discharged home on some combination of supplemental oxygen, bronchodilator, steroid, and/or diuretic therapy. In the longer term, children with BPD may develop asthma-like symptoms in childhood which are not uniformly responsive to bronchodilators. In later life, survivors of BPD also lack catch-up growth in lung function and have an accelerate decline in lung function. It is important to note that children born preterm who do not develop BPD are also at increased risk for these respiratory illnesses.

1. Home oxygen. Some infants discharged home from the neonatal intensive care unit (NICU) on supplementary oxygen may be weaned off within the first few months following discharge, whereas others may remain on oxygen for 2 years or more. Infants with BPD who are discharged home on oxygen are rehospitalized at twice the rate during the first 2 years of life compared to those who were not.

2. Respiratory syncytial virus (RSV). RSV is the most important cause of respiratory infection in premature infants, particularly in those with chronic lung disease. To minimize illness caused by RSV, VLBW infants should receive prophylactic treatment with palivizumab (Synagis) monoclonal antibody. The American Academy of Pediatrics (AAP) recommends treatment during RSV season for at least the first year of life for infants born ≤28 weeks’ gestation and for at least the first 6 months of life for those born between 28 and 32 weeks’ gestation. To prevent
illness caused by respiratory viruses, families should be counseled regarding good hand hygiene by all those in close contact with infants, avoidance of exposure to others with respiratory infections (especially young children during the winter season), and avoidance of passive cigarette smoke exposure. The influenza vaccine is also recommended for VLBW infants when they are older than 6 months; until then, care providers in close contact with the infant should strongly consider receiving the influenza vaccine.

3. Air travel. In general, air travel is not recommended for infants with BPD because of the increased risk of exposure to infection and because of the lowered cabin pressure resulting in lower oxygen content in the cabin air. If an infant’s PaO₂ is ≤80 mm Hg, supplemental oxygen will be needed while flying.

B. Immunizations. VLBW infants should receive their routine pediatric immunizations according to the same schedule as term infants, with the exception of hepatitis B vaccine. Medically stable, thriving infants should receive the hepatitis B vaccine as early as 30 days of age regardless of GA or birth weight. If the baby is ready for discharge to home before 30 days of age, it can be given at the time of discharge to home. Although studies evaluating the long-term immune response to routine immunizations have shown antibody titers to be lower in preterm infants, most achieve titers in the therapeutic range.

C. Growth. VLBW infants have a high incidence of feeding and growth problems for multiple reasons. Infants with severe BPD have increased caloric needs for appropriate weight gain. Many of these infants also have abnormal or delayed oral motor development and have oral aversion because of negative oral stimulation during their early life. Growth should be followed carefully on standardized growth curves (the World Health Organization [WHO] International Growth Curves 2006) using the child’s age corrected for prematurity for the first 2 years of life and then using the Centers for Disease Control and Prevention (CDC) standardized curves. Supplemental caloric density is commonly required to optimize growth. Specialized preterm infant formulas with increased protein, calcium, and phosphate (either added to human milk or used alone) should be considered for the first 6 to 12 months of life for infants who have borderline growth. ELBW infants may demonstrate growth that is close to or below the fifth percentile. However, if their growth runs parallel to the normal curve, they are usually demonstrating a healthy growth pattern. Infants whose growth curve plateaus or whose growth trajectory falls off warrant further evaluation to assess caloric intake. If growth failure persists, consultation with a gastroenterologist or endocrinologist to rule out gastrointestinal pathology such as severe gastroesophageal reflux disease or endocrinologic problems such as growth hormone deficiency should be considered. Monitoring for excessive weight gain is also recommended with adjustment of caloric density if weight has normalized to the 50th percentile or demonstrates a rapid acceleration over a short period of time. There is some evidence that links rapid weight gain of low birth weight (LBW) infants to excess accretion of adipose and subsequent risks of adult obesity and associated morbidities.

Gastrostomy tube placement may be necessary in a small subset of patients with severe feeding problems. Long-term feeding problems are frequent in this population of children, and they usually require specialized feeding and oral motor therapy to ultimately wean from gastrostomy tube feedings.

1. Anemia. VLBW infants are at risk for iron deficiency anemia and should receive supplemental iron for the first 12 to 15 months of life.

2. Rickets. VLBW infants who have had nutritional deficits in calcium, phosphorous, or vitamin D intake are at increased risk for rickets. Infants who are at highest risk are those treated with long-term parenteral nutrition, furosemide, and those with decreased vitamin D absorption due to fat malabsorption. Infants with rickets diagnosed in the NICU may need continued supplementation of calcium, phosphorous, and vitamin D during the first year of life. Supplemental vitamin D (400 IU/day) should also be provided to all infants discharged home on human milk or who are not taking 1 L of formula per day, which is enough to provide 400 IU/day.

D. Sensory issues that need special follow-up include vision and hearing.

1. Ophthalmologic follow-up (see Chapter 67). Infants with severe retinopathy of prematurity (ROP) are at increased risk for significant vision loss or blindness in the setting of retinal detachment. The risk of severe ROP is highest in the ELBW population in whom the incidence of blindness is 2% to 9%. Infants who have required treatment with laser therapy or bevacizumab (Avastin) warrant additional close monitoring to ensure that the infant’s retina becomes fully vascularized without complications.