eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Follow-up of the NICU Patient

Author: Michael P Sherman, MD, Professor, Department of Child Health, University of Missouri-Columbia School of Medicine; Director, Fellowship Training Program in Neonatal-Perinatal Medicine, NICU, Columbia Regional Hospital; Professor Emeritus, Department of Pediatrics, University of California, Davis, School of Medicine
Coauthor(s): Glen P Aylward, PhD, ABPP, Professor of Pediatrics, Southern Illinois University School of Medicine; Division Chief, Developmental and Behavioral Pediatrics/Psychology; Director, Center for Disorders in Development and Learning; Craig T Shoemaker, MD, FAAP, Chief of Pediatrics, Medical Director, Special Care Nursery, Division of Neonatology, Baylor University Medical Center at Dallas
Contributor Information and Disclosures

Updated: Jul 1, 2009

Introduction

Follow-up clinics for infants discharged from a neonatal ICU (NICU) are common in developed countries.^1,2  From their inception, NICU-related follow-up clinics have focused on outcomes of premature infants. Some clinics perform follow-up for medical conditions (ie, bronchopulmonary dysplasia, posthemorrhagic hydrocephalus); however, the intent in all NICU-related clinics is to determine neurodevelopmental outcomes. Numerous clinics do both, especially if the institution is part of a research network.^3,4  

The intent of the NICU-related follow-up should be several-fold. Less-than-acceptable outcomes may result in practice changes within individual NICUs. Most importantly, professionals in the clinic should direct "NICU graduates" to appropriate rehabilitative or social services if they are not aligned with optimal care in their community.

Presently, neonates born prematurely or with major malformations survive, whereas just a couple of decades ago, the same neonates born with these birth defects died. At the same time, pediatricians and family practitioners have less experience with the advances in NICU than they did 2-3 decades ago. In addition, during today’s clinical training, pediatric and family practice house staff have limited time to spend in the follow-up care of NICU-related graduates. The evaluation of preterm and term infants with complex conditions requires the involvement of professionals from multiple medical, rehabilitative, psychological, and social-service subspecialties.⁵

Follow-up of extremely low birth weight infants (ELBW), who have a birth weight less than 1000 g, from infancy to adulthood has revealed subtle neurodevelopmental problems that require evaluations and interventions that are more complex than previously appreciated.^6,7  A retrospective analysis of information on ELBW infants from the National Institutes of Child Health and Human Development revealed these patients have high use of special outpatient services, and efforts to improve these services are needed.⁸ Therefore, this article is intended to inform pediatricians, family practitioners, other health professionals, and families about the follow-up care of NICU graduates.

This revised chapter includes information about the new American Academy of Pediatrics (AAP) Statement on Hospital Discharge of the High-Risk Neonate,⁹ apprehension related to follow-up of the late preterm infant (ie, 32-36 weeks' gestation), concerns that grade I and II intracranial hemorrhages (ICH) have less favorable outcomes than previously appreciated, the results of new publications looking at ventricular dilatation after ICH, the use of brain-related imaging (ie, MRI) before hospital discharge as a predictor of outcome and early interventions, follow-up of infants with hypoxic-ischemic encephalopathy, and the relationship of preterm birth to autism. Resources for assisting families of the NICU patients and graduates are also updated.

For additional information and for discussion about related topics, please see the Further Reading section near the end of the article.

Criteria for Hospital Discharge

In 1998, the American Academy of Pediatrics (AAP) published guidelines related to "Hospital Discharge of the High-Risk Neonate."  In November 2008, the AAP released a similar and very well-written update.⁹  

The recently published AAP monograph places high-risk neonates into 4 categories: (1) the preterm infant, (2) the infant with special health care needs or dependence on technology, (3) infants at risk because of family issues, and (4) infants with anticipated early death.

The preterm infant

No set weight criteria for discharge have been established, and studies reveal that preterm infants can be safely discharged and well while weighing less than 2 kg.¹⁰  Discharge should be based on physiologic maturity and stability of the infant. The criteria for discharge generally include the following:

• Medical or surgical problems: Medical or surgical problems that require continued hospitalization must be resolved.
• Weight gain and feeding 
  • Weight gain of 15-30 g/d must continue over a reasonable time (several days to 1 wk). This weight gain should approximate fetal or early postnatal growth.
  • In addition, weight gain must be associated with the patient's ability to feed by mouth or by other methods (eg, feedings by means of gavage tube, gastrostomy, intravenous nutrition).
  • Feedings must be accomplished without any distress or problems.
  • The parents should demonstrate competence in using the method or technique selected for the infant’s nutrition.
  • Weight gain must have occurred while the infant was kept in an open environment (eg, crib). The infant must have been clothed appropriately, and the body temperature should be maintained in the normal range for numerous days in this environment (ie, thermal stability achieved).
• Training and comfort of parents and caregivers: 
  • Parents or other assigned caregivers must be trained adequately and comfortable in all aspects of the preterm infant’s care, including the administration of medications and the use of technical devices (eg, monitors, aerosol delivery equipment). Parents may pressure physicians to order a home monitor, but monitors are infrequently needed (see Apnea of Prematurity).
  • In the hospital, the parents' performance with their infant must be adequate before discharge.
  • The parents have minimal stress in caring for and in taking their infant home.
• Predischarge healthcare maintenance: Certain aspects of healthcare maintenance must be performed before discharge. 
  • Appropriate metabolic screening must be completed.
  • Anemia should be assessed, and its follow-up care must be established.
  • Patients who had prolonged stays may need to begin age-appropriate immunizations before discharge. Consult the 2006 AAP Red Book,¹¹ Immunization Information for Parents and Important Information for Clinicians from the AAP, or Immunization Schedules from the Centers for Disease Control and Prevention (CDC).¹²
  • All neonates in the neonatal ICU (NICU) should receive some type of hearing test before they are discharged from the hospital. The infants should have an appointment with an audiologist soon after discharge if testing in the hospital is abnormal.
  • For preterm infants, revised criteria have been published regarding the assessment of retinal vascularization by a trained ophthalmologist.¹³  For transferred infants, a qualified pediatric eye specialist must be available at the accepting facility. For outpatients, the infants must be seen by a qualified ophthalmologist according to the designed schedule.
• Postdischarge environment
  • An assessment of the postdischarge environment, possibly including an on-site evaluation of the home, is emphasized as part of discharge planning. This very effective evaluation is rarely performed.
  • The parents and the home environment must be suitable so that neither neglect nor physical abuse is likely to occur. Indicators of concern can include the frequency of parental visiting and the physical involvement of parents in care during the infant's hospital stay. Knowledge of poor parenting skills with other children, a history of marital discord, past or present substance abuse, or criminal activity requires that hospital and outside social services be involved. Reports may be required and submitted to local or state authorities. A contract may need to be signed by parents so benchmarks of care are set.
  • All medical equipment, termed "special technologies," required at home should be in place and in working order. Training of the caregivers should be such that they are experts. The caregivers must have emergency numbers to call when equipment malfunctions or supplies become meager.
• Support team and follow-up
  • A program of parental support, including in-home visits by healthcare professionals and assistance by family and friends, should be in place before discharge occurs. Community services should be informed and willing to help.⁸
  • Prior to discharge, the NICU program must be responsible for coordinating visits among different consultants that will occur after discharge.
  • A primary care physician (PCP) should have been identified during the mother's pregnancy; if not, one should be chosen early in the patient's hospital stay. The PCP must be familiar with the care of high-risk neonates. The PCP should help coordinate subsequent visits to subspecialists. The PCP also provides ongoing healthcare maintenance. The most important tasks of the PCP are ensuring adequate nutrition and proper growth and development of the patient. These duties may be performed in conjunction with follow-up programs of the NICU from which the patient graduates or with follow-up programs of private or governmental agencies that specialize in infant development.
  • Obstetric and neonatal attending physicians should begin verbal and written communication with the PCP, and vice versa, shortly after the baby's birth. Team members should periodically provide the PCP with verbal and written reports about the progress of the future NICU graduate so that information is available in the outpatient record.
  • An organized system must exist to assess the physical and psychological outcome of the NICU graduate.

The aforementioned criteria for discharge are applicable to all ill neonates and not just those born prematurely.

• Continuing medical care should be available after discharge.
• Child protective services should monitor visitation by the natural parents.
• The parents' participation in a rehabilitation program is essential in planning to reunite infants with their parents.
• The likelihood of success in reuniting infants with their increases if the parents comply with a structured rehabilitation program.

Discharge Planning

High-risk neonates from the initiation of intensive care should have an identified primary care physician (PCP). This person should become part of the discharge planning team. Unfortunately, finding a PCP and the degree of the PCP's involvement is a problem in NICUs throughout the United States. Often, medical funding for the infant (eg, Medicaid) makes identifying a PCP difficult for parents or caregivers early in the hospital stay. Moreover, the education of the parents may result in a lack of aggressiveness in securing the services of a PCP or the involvement of other community resources. 

Most importantly, the PCP must have training and experience in caring for various problems associated with high-risk neonates. A significant number of NICU graduates require the services of a PCP, a neurodevelopmental follow-up clinic, and pediatric medical or surgical subspecialists after discharge. The ideal follow-up clinic has physicians that can perform assessments of ongoing medical problems and a neurodevelopmental team that undertakes psychological evaluations and appropriate interventions (eg, team consisting of a neonatologist or pediatrician, psychologist, dietitian, physical therapist, occupational therapist, speech therapist, social worker). 

Each NICU should have a discharge-planning group comprising designated professionals. The members should include at least the following professionals: a discharge planner or case manager, one or more social workers, nursing representatives (eg, nurse manager, clinical nurse educator, neonatal nurse practitioners), physicians (always the attending neonatologist plus others), and community service representatives (eg, home health nurses, Medicaid case workers, protective services case workers, personnel from private or government-funded neurodevelopmental follow-up clinics). A frequent example is the medical follow-up of the extremely low birth weight (ELBW) infant who has ongoing bronchopulmonary dysplasia and requires a pediatric pulmonologist to work with the PCP.

Discharge planning should involve the above professionals. NICUs that maintain a high census and that care for high-acuity patients may have a discharge planner, a neonatologist, one or more nursing representatives, dietitians, physical, occupational and speech therapists, respiratory care practitioners, and representatives from the NICU follow-up clinic. On occasion, surgical subspecialists, pediatric subspecialists, or the PCP may be invited to the meetings to offer advice regarding infants with complex problems. A busy office practice often precludes the PCP from attending these meetings. Nevertheless, PCPs should be given periodic reports on the progress of their future patients after every meeting and must be willing to assume care upon discharge.

The time of day, the designated day of the week, and the frequency of the meetings associated with discharge planning depend on the needs of a given NICU. For NICUs with large populations, the frequency, day, and the time depend on having an optimal number of team members present. For small NICUs, formal discharge-planning rounds may be inefficient. Because of rules related to the protection of patients' information, certain participants (eg, Medicaid and protective services case workers) may need to discuss their cases first and then leave when their patients are not being discussed. 

Few published reports make recommendations about the discharge-planning process. One summary is the 2008 policy statement from the American Academy of Pediatrics (AAP) Committee on Fetus and Newborn.⁹

Hospital Discharge Guidelines

1. Parental education
2. Completion of appropriate elements of primary care in the hospital
3. Development of management plan for unresolved medical problems
4. Development of a comprehensive home care plan
5. Identification and involvement of support services
6. Determination and designation of follow-up care

Parental education

A structured teaching plan must be individualized for the primary caregivers to care for the child. Each infant has unique needs, and the education program should be directed at those needs. A checklist is essential to accomplish all of the required teaching needs (eg, cardiopulmonary resuscitation, gastrostomy feedings, total parenteral administration, monitor use). The goal of this education is to ensure that the parents are capable and confident in caring for their infant at home. It may be appropriate for caregivers to stay overnight and provide care with minimal staff interventions. The staff providing care should not appear overprotective. 

Two or more caregivers in the home must receive this training. This training allows respite for the primary caregiver. A young mother with other small children and no grandmother or husband can be particularly stressed. The role of confounding factors associated with siblings in the home must be considered in the teaching.

No matter how complex the problem, the appropriate educators must be identified to provide the training. For extremely complicated care situations (eg, those in infants with a tracheostomy), parents should have a rooming-in experience before discharge occurs. This is probably a good practice for all families before they go home with their infant but is especially important for infants who have ongoing, complex problems. Home visits by experienced home healthcare professionals and/or follow-up telephone calls are essential for the success of the transition process.

Completion of appropriate elements of primary care in the hospital

The implementation of primary care includes more than just identifying a PCP within the first week of the patient's hospitalization. In and out of the hospital, primary care involves an assessment of the infant's nutrition and growth, immunizations before and after discharge, indicated respiratory syncytial virus (RSV) prophylaxis, car and home safety, and neurodevelopmental outcomes (including hearing and vision screening). 

Among the most important follow-up is monitoring for serious anemia and continuing assessment of retinopathy until both are resolved. In-depth nutritional evaluation is mandatory for infants who received prolonged parenteral nutrition, who had GI anomalies, and who may have either an inborn error of metabolism or other metabolic/biochemical disorders.

Development of management plan for unresolved medical problems

A list of unresolved problems must be developed during the patient's hospital stay, and this list must be made available to the PCP. Ongoing conditions should have been completely diagnosed, and a management plan for diseases that persist must be established at the time of discharge. The plans for ongoing care by the PCP must be transmitted in detail. The current treatment plan and all medications the infant is receiving should be conveyed to the home health professionals and the PCP before discharge. Resolved problems should also be identified at the time of discharge because some unanticipated complication may arise. Individual infants have received the best in-home and follow-up care with this method.

Development of a comprehensive home care plan

The recently AAP established guidelines for technology-dependent infants are helpful in the discharge-planning process.⁹  Publications about the care and outcomes of NICU graduates requiring complex technology are limited.^27,28,8 The plan of care in the home should have the following elements:

• Identification and training of in-home caregiver
• Planning for optimal nutrition and follow-up (eg, total parenteral nutrition, gastrostomy feeds)
• A list of equipment, supplies, and resources that are needed at home
• Referrals to home healthcare professionals and community resources that can provide ongoing assessments and care after discharge and the full knowledge that the PCP understands what resources have been initiate
• An assessment of the home environment to determine that it is suitable for care and to determine what improvements must be made before discharge
• A plan for emergency care and transport should the need arise
• Assessment of financial resources identified by using either indemnified insurance or governmental programs to finance future hospital, office, and home healthcare needs: When appropriate, Social Security Income (SSI) must be applied for during the hospital stay; other free services (eg, Shiners' Hospitals) must be underway at discharge

PCPs must be aware of these elements, especially when they do not participate in their implementation.

Identification and involvement of support services

The ability of the primary caregiver and other family support members to deliver care must be assessed before discharge. Ongoing assessment of the caregiver's physical and emotional abilities to continue providing care at home must be established. In-home evaluations regarding the availability of supplies, medications, complicated technologies, and nutritional support must be started before discharge. Healthcare workers who provide ongoing home evaluations and who can identify new problems are essential for a favorable long-term outcome for the NICU graduate.

Determination and designation of follow-up care

The discharging neonatologist has overall responsibility for follow-up care at discharge. Ongoing communication between the neonatologist and the PCP during the hospital stay and at discharge improves outcomes for the infant.

Early identification of a PCP is important. In the ideal circumstance, the PCP reviews the records, examines the infant, and meets with the family before discharge. In the era of managed care, the busy office practice of a pediatrician or family practitioner may not allow for such a review before discharge. In some cases, the skills of the primary care provider are limited relative to the complex problems of the infant. Therefore, appropriate follow-up care with surgical and pediatric subspecialists is necessary. Teamwork is the key to success in regards to discharge planning and follow-up.

Most important among the subspecialist visits is a follow-up appointment with a neurodevelopmental specialist. Although such an appointment may be in the distant future, a list of scheduled and unscheduled (but anticipated) appointments should be made and given to the parents and PCP before discharge.

The discharge-planning process is usually well established at tertiary NICUs; however, level II nurseries should also conduct such activities. Infants may be transported close to their home for convalescent care, and the staff at the level II nursery is responsible for determining the infant's health status (eg, the absence of potentially blinding retinopathy of prematurity [ROP]) before discharge. If retinal pathology still is active, an appropriate discharge plan must be formulated.

Arrangements for follow-up appointments may be made locally; however, this is not always possible. Some level II nurseries may be in relatively rural areas, and the infant still needs to return to the tertiary center for certain services (eg, ophthalmologic examinations, hearing assessments, developmental follow-up). In rural areas, home services may also be limited, which means that the PCP has additional responsibility in evaluating the transition to home care.

Finally, the NICU staff is responsible for assessing the performance of a home health care agency and of its workers' abilities to provide quality care to the infant who is technology dependent. If an agency's staff does not perform properly, they should be so informed. If the quality of care does not improve, alternative arrangements for care must be sought.

Healthcare Maintenance of the NICU Graduate

The major goals of the pediatrician or family practitioner who monitors a neonatal ICU (NICU) graduate include the following:

• To provide an ongoing assessment of growth
• To evaluate the adequacy of nutrition
• To deliver preventive care
• To periodically examine the infant's, child's, or adolescent's motor, intellectual, and behavioral development

This section mainly covers the assessment of growth and nutrition and the delivery of preventive care. Periodic examination of development is discussed in the Developmental Follow-up sections below. Another important aspect of healthcare maintenance of the NICU graduate is health supervision and anticipatory guidance.

Assessment of Growth

The first duty of the primary care physician (PCP) is to accurately monitor the growth of the NICU graduate.^29,30,31 Therefore, the patient's weight, length, and head circumference must be plotted on appropriate growth charts and evaluated over time. Growth should be plotted for infants who were born prematurely after it is corrected for the patient's gestational age at birth. Special growth charts are available for this purpose.³² Growth charts for term infants hospitalized in the NICU are also available.³³

In infants who are born prematurely, weight gain and other growth parameters usually start accelerating by 40 weeks’ postconceptual age. Measurement and documentation of head growth, a predictor of future outcome,^34,35 is especially important in this high-risk population. In preterm infants, head growth correlates with MRI findings and neurodevelopmental outcome.³⁶  An assessment of head growth is especially important when a history of a chromosomal disorder, brain insult secondary to hypoxic-ischemic encephalopathy, or a metabolic disease is present.

A group of preterm babies that need special attention include those who weigh less than 1500 g at birth (very low-birth-weight [VLBW] infants). The National Institute of Child and Human Development (NICHD) Neonatal Research Network has reported that 97% of VLBW infants and 99% of infants who weigh less than 1000 g at birth (extremely low birth weight [ELBW] infants) had weights less than the 10th percentile at the postmenstrual age of 36 weeks.³⁷ This growth failure begins during the NICU hospitalization. It is now the focus of many providers who are concerned about the late consequences of this poor growth that occurs during a critical period of brain development.

Growth failure may have many origins in NICU graduates.^38,39  As noted above, infants who weigh less than 1500 g at birth must undergo frequent assessments of growth. The PCP should know whether preterm infants or those small for gestational age (SGA) are gaining at least 20 g/d before discharge. If growth is <20 g/d, a plan should be in place before the patient is discharged from the NICU and communicated to the PCP, who should carefully follow up the patient's growth. A prospective study by the NICHD of infants who weighed 500-1000 g at birth showed that their growth in the NICU influenced subsequent neurodevelopmental and growth outcomes in positive or negative ways.⁴⁰ The PCP should be aware of their patient’s growth characteristics in the NICU.

The type of nutritional support may also help in identifying infants at risk for growth failure. These infants include those who are breastfed, infants given special formulas, and infants receiving total parenteral nutrition for longer than 4 weeks or are still receiving total parenteral nutrition at discharge. Despite some increased risks associated with breast milk–related nutrition in ELBW infants (eg, osteopenia of prematurity), neurodevelopmental outcomes at age 18 months are more favorable in breastfed infants than in others.⁴¹ Infants requiring nasogastric tube or gastrostomy feedings after discharge are at significant risk for impaired growth.

Infants may also be at risk for nutritional deprivation depending on their disease states. Common neonatal conditions for which an evaluation for growth failure is required include chronic lung disease of prematurity (ie, bronchopulmonary dysplasia), severe CNS injuries or birth defects, congenital heart disease, short bowel syndrome, esophageal and intestinal anomalies, chronic renal disease, inborn errors of metabolism, and chromosomal and/or major malformation syndromes.

To rectify the cause of growth failure, the PCP must understand its origins, especially in the very preterm infant.⁴²  Many examples illustrate why growth failure occurs in term infants that graduate from the NICU. An infant with congenital heart disease may have growth failure because his or her feeding difficulties are associated with congestive heart failure and an increased work of breathing. Corrective surgery may be the only solution for this condition.

An infant with severe perinatal asphyxia may be unable to suck and swallow because of brain injury. Such an infant may require a permanent gastrostomy (and gastric fundoplication) to ensure adequate nutrition. Even when this is accomplished, the brain insult still may result in poor growth secondary to hypothalamic and pituitary effects or other yet-undefined consequences of severe cerebral damage.

A premature infant recovering from severe bronchopulmonary dysplasia may have reduced growth because of pulmonary disease, which increases the work of breathing, and inadequate protein intake. Severe chronic lung disease in the NICU graduate is commonly associated with gastroesophageal reflux (GER). The diagnosis of GER was recently reviewed.⁴³ In infants with GER, alleviating esophageal pain with H2 antagonists or proton-pump inhibitors in conjunction with prokinetic agents may mitigate the problem and promote increased feeding volumes and weight gain.

Convalescent infants who had severe necrotizing enterocolitis (NEC) may have an insufficient epithelial surface or a damaged mucosa that does not allow adequate absorption of nutrients from the gut. Persistent poor growth in these infants may require a return to partial parenteral nutrition.

Graduates of the NICU often have accelerating growth patterns after discharge. This is particularly true for preterm infants.⁴⁴ Head growth frequently exceeds weight gain and linear growth. Careful attention must be paid to exclude posthemorrhagic hydrocephalus as the cause of rapid increases in head circumference. After ultrasonography reveals that ventricular size is stable or declining after intraventricular hemorrhage, the risk of posthemorrhagic hydrocephalus is small. This issue is generally resolved before the patient is discharged from the NICU.

Controversy surrounds the age at which catch-up growth is complete for infants who were born prematurely; many clinicians now believe that catch-up growth is not complete until age 2.5-3 years. In some SGA infants, body mass may rapidly increase, but a substantial number have little catch-up growth.⁴⁵ These SGA infants should be referred to a pediatric endocrinologist because therapy with recombinant human growth hormone may be useful in some.

A current concern involves the rate of catch-up growth and its association with an increased risk of obesity and heart disease in later life.⁴⁶ In part, the pathophysiology of low birth weight and later adult disease is derived from the Barker hypothesis.⁴⁷ Emerging data are causing a re-examination of the best rate for catch-up growth and of the strategy to avoid the consequences low birth weight.^46,48 Greer presents a critical review of this topic and recommends postdischarge nutrition.⁴⁹  The benefits of breastfeeding appear to substantially affect adult diseases associated with the Barker hypothesis.⁵⁰  Continued and prolonged use of breast milk for nutrition after discharge is associated with higher Bayley Mental Development Index scores in ELBW infants assessed at 30 months.⁵¹

In any infant with a growth rate in the lower percentiles of the curve or whose growth curve flattens or decelerates should have the causes assessed. If improved nutritional support does not reverse the growth pattern, or if diagnostic studies do not reveal an obvious cause, referral to an endocrinologist, gastroenterologist, and/or dietitian is indicated.

Evaluation of Nutrition

General assessment

Evaluation of nutritional sufficiency includes more than a simple assessment of body measurements (eg, weight, length, and head circumference). The evaluation includes studying the patient's fluid and mineral intake, an appraisal of caloric and substrate consumption, and, at times, indirect measurements of proper body composition (eg, skin-fold thickness, certain biochemical determinations made by using blood specimens). A complete evaluation helps in identifying any excesses or deficiencies in nutrient consumption.

The PCP must also monitor the route by which nutrition is provided. Parenteral nutrition, enteral nutrition, or both may be used to attain adequate nutrition. Inadequacies in delivering nutrients by either the parenteral or enteral route must be recognized. The PCP may be untrained or inexperienced in this type of nutritional evaluation. The role of follow-up care of the NICU graduate must often include a pediatric dietitian, and a specialized follow-up clinic may be needed for certain infants.

When access to a follow-up clinic and a pediatric dietitian is limited, the PCP may need to use a home feeding diary and/or a nutritional assessment sheet to gather additional information.⁴⁴ In this manner, the PCP may be able to accurately measure the exact caloric intake and the composition of substrate that the infant is consuming.

Prolonged intubation and repeated insertion of gavage tubes can result in aversion to oral feeding.⁵² Deviations from a normal suck and swallow response may include a tonic bite reflex, an abnormal tongue thrust, or a hyperactive gag. More important than these findings, and too often observed, is the presence of a dysfunctional suck, swallow, and breathing pattern that results in hypoxemia, apnea, or both during oral feeding. This problem is often observed in ELBW infants.

Parental anxiety adds to the problem. In this setting, observation of infants by an occupational therapist or nurse specially trained to recognize feeding problems is an excellent method to make the diagnosis and treat these infants properly. Cineradiography of the suck and swallow mechanism often helps in this process. Diagnostic tests to exclude GER as a contributor to abnormal feeding behavior are also frequently necessary. The NICU team is responsible for making these assessments and for developing a treatment plan before discharge. The PCP must be thoroughly aware of this assessment to understand the pathophysiology of the disorder, and he or she must comprehend the likelihood of success with the therapy applied.

Finally, stool passage and the composition of the stools may be useful in assessing the adequacy of nutrition. Abdominal distension and oily, mucoid, explosive, or watery stools should heighten the suspicion of epithelial absorptive problems in the intestine. Carbohydrate and protein intolerance (an inability to digest food or a true allergy) must be considered in infants with abnormal patterns of stool passage, and diagnostic tests are indicated. Referral to a pediatric gastroenterologist may be appropriate if test results do not indicate a diagnosis or if interventions do not alleviate the problem.

Nutritional assessment begins with a complete history and physical examination.⁵³ Evaluation of the patient's general health status, heart rate, breathing rate, temperature control, and fluid balance are parts of this examination. Also included are anthropometric measurements, including weight, length, head circumference, and sometimes skin-fold thickness, which are plotted over time.

In the first 3-4 months after birth, normal weight gain averages 15-40 g/d and then declines, reaching about 5-15 g/d by the age of 12-18 months. From a postmenstrual age of approximately 40 weeks until month 4 of postnatal life, weight proportionally increases more in infants who were born prematurely than in those who were born at term. Increases in weight versus length may differ in NICU graduates who are having problems with adequate nutritional intake, and a comparison of the 2 measurements (eg, length increasing faster than weight) can provide evidence of nutritional sufficiency.

The rate of accelerated growth in preterm infants is still larger than that in term infants, but the magnitude is far less. In the months after preterm infants are born, the crown-heel length may incrementally increase by 0.8-1.1 cm/wk, whereas term infants gain a mean of 0.7-0.75 cm/wk. By the age of 12-18 months, the gain in length declines to 0.75-1.5 cm/mo.

The largest frontal-to-occipital plane is used to determine the patient's head circumference. For preterm infants, the increase in head circumference is in the range of 0.7-1 cm/wk, whereas the increase in term infants averages about 0.5 cm/wk during the immediate postnatal period. Increases in head circumference of more than 1.25 cm/wk suggests ventricular dilitation (ie, hydrocephalus or other causes of increased intracranial pressure [eg, subdural hematoma]). Increases in head growth more accelerated than these may be related to conditions other than posthemorrhagic hydrocephalus, such as autism or genetic or metabolic disorders. A rapid deceleration in head growth occurs by age 12-18 months, after which, the increase is only 0.1-0.4 cm/mo.

During the first 3-6 months after discharge, the velocity of growth related to weight, length, and head circumference has been inadequately studied in NICU graduates. The reason may lay with difficulties in establishing the values for healthy preterm or term infant. Investigators would need to address birth-weight categories, gestational ages, sex, race, nutritional methods, countries where the studies are performed, and ongoing diseases that affect growth.

A study of infants with birth weights of 750-2500 g in Brazil showed substantially growth deceleration by age 12 weeks.⁵⁴ Ehrenkranz et al reported on the longitudinal growth of hospitalized VLBW infants in the United States; however, the duration of study was limited to near-term gestation.³² Therefore, the study lacked information about growth after hospitalization, which is crucial information needed by the PCP.

Most infants gain weight and grow with an intake of 108 kcal/kg/d. Infants born prematurely usually require 110-130 kcal/kg/d for sustained weight gain and growth. Protein requirements may also be increased.  For these preterm infants, the following simple equation may be used to calculate their increased needs: Daily intake = 120 kcal/kg X (ideal weight for actual height/actual weight), where both weights are in kilograms.

In extraordinary circumstances, indirect calorimetry may be required to ascertain an infant's energy needs. These measurements include oxygen consumption, production of carbon dioxide, and elimination of urinary nitrogen. These techniques require the assistance of a tertiary care center.

Specific evaluations

Specific assessments of the NICU graduate include evaluations of fluid balance, the mineral content of the blood and bone, the patient's energy intake, and the nutrient composition consumed by the patient. Fluid balance is important in NICU graduates with serious pulmonary, cardiac, GI, and/or renal problems. Fluid restriction may result in poor growth unless the patient is fed high-caloric formula, fortified breast milk, or breast milk supplemented with formula intake to compensate. In the converse, excessive fluid may cause edema. The disease itself or diuretic therapy may affect the mineral content of the blood.

Assessment includes not only a determination of blood electrolyte concentrations but also a measurement of acid-base balance. Pulmonary or cardiac disease can be associated with clinically significant respiratory acidosis and renal compensation. Diuretic therapy may accentuate this problem. This is particularly true for low concentrations of potassium and chloride in the blood and a contraction alkalosis in association with severe chronic lung disease of prematurity (ie, bronchopulmonary dysplasia).

Diuretic therapy may also cause further disturbances in calcium and phosphorus homeostasis (eg, low concentrations of total or ionized calcium), diminish plasma phosphorus content, and elevate alkaline phosphatase activity in the blood. These chemical findings in the blood frequently reflect osteopenia in preterm infants. Osteopenia of prematurity is a defined disorder of diminished bone mineralization often observed in VLBW infants. A study in the United Kingdom revealed no consistent practices related to osteopenia in preterm infants.⁵⁵  The disease can result in rickets or fractures of the ribs and long bones.

Recommendations for the intake of calcium salts, phosphorus, and vitamin D that can diminish the risk of fracture have been established.⁵⁶  If fractures do occur after discharge, this cause must be distinguished from physical abuse. Osteopenia of prematurity has a complex etiology that includes rapid bone growth with inadequate intake or metabolism of calcium, phosphorus, vitamin D, and protein. Correction involves treating the specific deficiencies. Renal disease with sodium wasting, excess bicarbonate losses, and poor retention of calcium and/or phosphorus can additionally complicate the clinical picture. The optimal method of monitoring bone mineralization in preterm infants with birth weights less than 1500 g is unsettled and may involve biochemical analyses, dual X-ray absorptiometry (DEXA), and/or ultrasonography;^56,57 the PCP should be aware of the methods of assessment.

Other deficiency states are observed in NICU graduates and include a lack of specific vitamins, iron and trace minerals, carnitine, essential fatty acids, and protein. These deficiencies are not discussed in detail in this article; however, specific deficiencies are covered briefly below. Most deficiencies are avoided with the use of preterm formulas and/or fortified breast milk. Improved fortifiers, if available and if used before and after hospital discharge, enhance biochemical components associated with growth and affect postnatal growth itself.^58,59,60

• Vitamin K deficiency can result in a bleeding disorder from reduced synthesis of liver-related coagulation factors.
• Folate deficiency can be associated with a megaloblastic anemia, dermatitis, and diarrhea.
• Iron deficiency is the most important cause of anemia in NICU graduates. Therefore, infants with iron deficiency are often receiving iron and vitamin supplementation at the time of discharge. A recent study concluded that iron supplementation in breastfed infants is feasible and increases iron status without increasing the hematologic status.⁶¹
• Although infrequent, zinc deficiency is associated with growth failure, defective host defenses, slow wound healing, and acrodermatitis enteropathica. Exclusive breastfeeding of ELBW infants is the scenario that most often results in zinc deficiency.
• Carnitine deficiency can cause failure to thrive, cardiomyopathy, encephalopathy, and recurrent infections. This deficiency is most often recognized in infants who are receiving only parenteral nutrition. For this reason, in infants receiving long-term total parenteral nutrition, the solution should be supplemented with carnitine.
• Protein-related malnutrition is among the most serious nutritional problems encountered in patients in the NICU before and after discharge.⁶²
  • Protein deficiency is associated with slow growth, hypoproteinemia and edema, lethargy, impaired wound healing, and an increased incidence of infection.
  • Measuring plasma prealbumin and albumin levels is useful in severe protein-deficiency states, but a strategy for early detection of the deficiency state is problematic. For a long time, French pediatricians have used a BUN value of more than 5 mg/dL as an indication of adequate protein anabolism, but simple measurements of adequate protein intake and metabolic use are, for the most part, lacking.
  • Exclusive breastfeeding of ELBW and VLBW preterm infants creates a likelihood of protein-energy malnutrition, but the use of fortifiers and a publication showing an improved neurodevelopmental outcome in ELBW infants who received human milk should allay concerns about this risk.⁵¹ Early use of intravenous solutions containing amino acids has been shown to prevent the negative protein balance that can begin shortly after birth in the VLBW and ELBW population.⁴²
• A prospective double-blind randomized controlled trial showed that a human milk fortifier enhanced the growth of preterm infants.⁵⁸ Use of human milk fortifier may be incorporated into the postdischarge care of preterm infants. Hay et al wrote an overview of the nutritional needs of ELBW infants.⁶³

Delivery of Preventive Care

Healthcare maintenance is the essential function of the PCP. Assessment of growth and nutrition is an integral part of that function. Other functions include education regarding safety concerns; prevention of infectious diseases by means of immunization; and evaluations of vision, hearing, and other aspects of neurologic development. Problems with infant-parent bonding are also the PCP's concern. The neurologic and emotional aspects manifest in NICU graduates are reviewed in subsequent sections of this article.

Two important preventive measures may begin in the NICU. The first preventive therapy is immunization. To obtain current information about the immunization schedule for infants, see the AAP Red Book¹¹ and Immunization Schedules from the CDC (2007).¹²

The second measure is education regarding car seat safety and the proper use of car seats. Data are insufficient to prove the "car seat challenge test" before hospital discharge, which assesses oxygenation while the infant is in the care seat.⁶⁴  The PCP should also review car seat safety during the initial office visit. Before infants are discharged from the NICU, their parents or guardians should be instructed about appropriate use of a car seat. Preterm infants should be placed in their car seat, and the absence of airway obstruction or apnea while they are seated should be ascertained before the leave the hospital.

The PCP also has a responsibility to aid in home safely and to prevent crib death (eg, by means of Back-to-Sleep campaign, by advising families to avoid cobedding or sleeping). The PCP should review recent recommendations⁶⁵ and the success of the recommendations for supine sleeping.⁶⁶

If indicated, immunizations should be started prior to hospital discharge.⁶⁷ The PCP continues or starts immunizations during follow-up care. The practice of professionals who deliver in-hospital care of VLBW may lag behind current recommendations for immunizations.⁶⁸ One reason for this lag may be the concern that apnea may increase within 72 hours after immunizations^69,70 or that febrile responses may occur.⁷¹  

The cardiorespiratory status of infants with chronic lung disease may worsen for approximately 48 hours after immunization.⁷² Whether ELBW infants can respond to immunizations within 2 months of birth (eg, 2 mo after birth for an infant born at 23 weeks' gestation [ie, postconceptual age of 31 wks]) is controversial. Some investigators believe that immunizations should be given at or after 35 weeks’ postconceptual age and that this timing enhances the immune response. PCPs must be aware of problems associated with the administration and the effectiveness of immunizations given to ELBW infants.

Preterm and other high-risk infants may meet guidelines for the administration of palivizumab. This monoclonal immunoglobulin G is given intramuscularly to reduce the severity of respiratory syncytial virus (RSV) infections.⁷³ In 2003, the AAP published guidelines for prophylactic injections of palivizumab.⁷⁴ In most communities, RSV season usually begins in late October or November and ends been March and May. The use of palivizumab has been cost effective in preterm infants born at less than 30 weeks' gestation⁷⁵ and in preterm infants with a postconceptual age of 32-35 weeks.⁷⁶

Health Supervision and Anticipatory Guidance

Review of the patient's neurodevelopment is one of the PCP's primary tasks, and the provider must understand how the patient's physical and mental disabilities affect the parents and the family as a whole. The emotional well-being of the child and the family is critical to a successful life.

The PCP should coordinate care for patients leaving the NICU,⁷⁷ but, in reality, this infrequently occurs. The PCP is also responsible for the follow-up care of any infant who has an abnormal result on a hearing screen or ophthalmologic examination before hospital discharge. Many states require that all infants undergo hearing screening before discharge. A vital role of the PCP is assessment of anemia of prematurity. Periodic measurements of hemoglobin levels, hematocrit levels, and reticulocyte count is an important job transferred to the PCP. The PCP also has the responsibility of keeping track of referrals to subspecialists for the numerous problems that an individual NICU graduate may have.

The PCP must ensure that healthcare insurance, whether funded privately or publicly, is available to the infant. The physician and the family must work together to obtain supplemental Social Security benefits based on the infant’s disabilities. In addition, the PCP must refer the infant to the proper community-based and education-based services appropriate to the patient's disabilities. Finally, the PCP must ensure that supplies and services are continuously available to technology-dependent infants.

Parents should be counseled regarding the sleeping position of their preterm or term infant. In its Back-to-Sleep program, the AAP recommends supine sleeping for term infants; this positioning has significantly reduced rates of sudden infant death syndrome (SIDS).⁷⁸ The risk of SIDS is increased in preterm infants (birth weight <2500 g) and SGA infants who sleep in a prone or lateral recumbent position versus the supine position.⁷⁹ Therefore, for preterm and term infants, "back is best."^80,81  Parents and PCPs must be aware that "back is best" is associated with an increased risk of plagiocephaly and torticollis, and interventions to treat these conditions must be undertaken.⁸²

Personal communication between the PCP and parents about their NICU graduate is essential to the physical and emotional well-being of the infant and family. Many questions are likely to arise before discharge, during the first office visit, and over the next months and years. Issues may include keeping the home warm, dressing the infant, allowing visitors, taking the infant outside, avoiding direct sun exposure, and flying to visit friends or family. Other issues may be more specific than these and related to infant's behavior or health.

Sample questions include the following:

• Why does my baby make grunting sounds ("preemie" noises)? Are these sounds abnormal?
• Why does my baby's nose seem stuffier now than during my baby’s stay in the hospital?
• My baby seems to sneeze and cough a lot. Is this a sign of illness?
• When and how do I take my baby's temperature?
• Is it bad that my baby has not had a bowel movement for 2 days?

A predischarge meeting of the NICU staff and the family can help ease the transition home. That said, the PCP must realize that questions such as those listed above are common and may seem numerous. Many answers simply involve common sense. To the authors' knowledge, no complete collection of the typical questions parents asked has been published. Therefore, few or no reference sources are available for PCPs. Practical experience is perhaps the only way to become comfortable in addressing many of these questions.

Many concerns may emanate from the parents' perception that their child is vulnerable to a number of physical and intellectual challenges. This view may be obvious to both the PCP and the parents at the time of discharge. The PCP must recognize patients at risk of becoming vulnerable children because the parents feel guilt or are overprotective. This topic is important enough that it is covered specifically in The Vulnerable Child.

Parents may wish to learn more about their baby's potential problems or disease than what time allows in the NICU or in the physician's office. The parents may seek information about community, state, or national resources to help their infant or child. Tertiary sponsored follow-up clinics can also be resources, as can governmental or private agencies involved in specialized care or rehabilitation. Helping parents to gain access to information or resources is an important function of the PCP. Resources for Parents and Caregivers provides resources that may be useful to parents.

Assessment and Management of Medical Disorders in the NICU Graduate

Medical disorders in neonatal ICU (NICU) graduates cover a wide range of disease states. The conditions covered in this article include disorders uniquely encountered in premature infants.^30,31 The care of infants with major malformations, chromosomal disorders, syndromes, or sequences, disorders of metabolism, and infectious diseases are covered in other articles in the Pediatrics section of the eMedicine journal.

Anemia of prematurity

Anemia of prematurity is one of the most common and important problems that the primary care physician (PCP) must address in the NICU graduate. After birth, hemoglobin concentrations decrease more rapidly and more severely in premature infants than in term neonates, and the lowest hemoglobin levels are observed in extremely low birth weight infants (ELBW) infants.⁸³

The PCP absolutely must know the patient's hemoglobin value, hematocrit, and reticulocyte count at the time of discharge. The PCP must be aware of the sign and symptoms of anemia and manage it appropriately. In a hospital-based study, liberal use of blood may have improved neurologic outcome compared with restricted transfusion.⁸⁴ The PCP should frequently (eg, weekly or biweekly) obtain hemoglobin levels, hematocrits, and reticulocyte counts after discharge until they suggest that the patient's anemia is resolving. For ELBW infants, hematocrits usually stabilize and begin to rise by age 3-6 months. Treatment of severe anemia after hospital discharge is discussed in Anemia of Prematurity.

Apnea and bradycardia of prematurity

The National Institute of Child and Human Development (NICHD) reviewed issues related to apnea of prematurity.⁸⁵ The severity of apnea and bradycardia in prematurely born infants is inversely proportional to their gestational age. Causes of apnea include immature central regulation of breathing; obstruction due to immature airway reflexes; and/or delayed coordination of sucking, swallowing, and breathing responses. However, the PCP must consider other diagnoses when apnea and/or bradycardia are the presenting signs or symptoms after discharge.

Such conditions include, but are not limited to, profound anemia, severe gastroesophageal reflux (GER), hypoxia or bronchospasm related to chronic lung disease (CLD), infection (especially respiratory syncytial virus (RSV) infection), malfunctioning or infection of a ventriculoperitoneal shunt, and seizures. Apnea can recur in preterm infants after they are hospitalized or after they receive general anesthesia for a surgical procedure (eg, inguinal hernia repair).

Apnea and bradycardia of prematurity may occur at home, even in an infant who was free of apneic episodes for more than a week before discharge.⁸⁶ In this instance, the PCP may have to consider rehospitalization if an acute life-threatening event has occurred. If no cause for the apnea is found and if the infant is not receiving a methylxanthine, use of theophylline or caffeine may be considered in conjunction with a cardiorespiratory monitoring. Some premature infants may be discharged with cardiorespiratory monitoring and one of these medications. 

Much discussion has focused on whether home monitoring helps in preventing death in preterm infants.⁸⁰ Because of advertising in the lay media, parents may request or demand home monitoring. Clinicians must explain to such parents that home monitoring does not prevent sudden infant death syndrome (SIDS), although monitoring for apnea and bradycardia might avert the sequelae of hypoxia-related events.⁸⁰

Late causes of apnea, as described above, should be excluded before an infant is discharged with home monitoring. For infants discharged with home monitoring and methylxanthines, the PCP may wish to have the infant outgrow medication during monitoring. Regardless of whether the methylxanthine is weaned in this manner or formally stopped, monitoring must be continued for at least 1-2 weeks before its cessation is considered.

One criterion for stopping home monitoring is a 4-week to 8-week period with no clinical apnea, no cyanotic episodes, and no history of monitor alarms. Some PCPs may wish to download and review event recordings before stopping monitoring. A scheme for judging the cessation of home monitoring has been published.⁸⁷ The AAP suggests that home monitoring for a preterm infant with apnea of prematurity may be stopped by 43 weeks' postmenstrual age.⁸⁰ Infants who were born at 22-24 weeks of gestation may not be ready for discharge until this postmenstrual age. A study in Israel showed that 80% infants with apnea of prematurity terminated monitoring at 40-44 weeks postconceptual age, and the authors recommended that home monitoring be discontinued at 45 weeks.⁸⁸

Chronic lung disease of prematurity

Initially called bronchopulmonary dysplasia, chronic lung disease of prematurity and its manifestations have changed over recent years.⁸⁹ The incidence of chronic lung disease of prematurity, or the "new bronchopulmonary dysplasia," is more than 60% among infants who weighed 500-600 g at birth,^89,37 and its incidence approaches 100% in those who weighted less than 500 g at birth.

Investigators recently reviewed the pathophysiology of the "new bronchopulmonary dysplasia,"^90,91 and a comprehensive overview has been published.⁹²

Factors that define chronic lung disease include a typical radiographic appearance of cystic emphysema and fibrosis or subtle changes of diffuse interstitial edema and a requirement for inspired oxygen at the 28th day of life or the 36th week of postconceptual age. The preferred definition may be an oxygen requirement at 36 weeks’ postconceptual age.

The infant presenting in the PCP’s office while receiving home oxygen therapy and multiple medications is at high risk for developing cardiopulmonary complications after discharge. To prevent cor pulmonale, intermittent or persistent hypoxemia and clinically significant hypercarbia must be prevented after discharge. A pediatric pulmonologist, in addition to the PCP, should monitor infants discharged home with considerable need for oxygen and substantial renal correction of respiratory acidosis.

Home oxygen therapy is a safe and cost-effective treatment and may reduce complications (eg, cor pulmonale) in infants with chronic lung disease.^93,94 Oxygen therapy also appears to facilitate the growth of infants with bronchopulmonary dysplasia.⁹⁵

In the PCP’s office, oxygen saturations must be monitored with pulse oximetry. The level of inspired oxygen required to prevent hypoxemia indicates the severity of disease and whether the patient's condition is improving.

Adjunctive therapy for bronchopulmonary dysplasia may include inhaled bronchodilators and/or steroids, oral corticosteroids, and diuretics.⁹⁶ Management of chronic lung disease may involve oxygen, medications, complex technologies, and attention to superb nutrition.^97,98,99 Issues have arisen regarding whether corticosteroids inhibit normal growth of the lung and brain and whether it causes future pulmonary or neurodevelopmental disabilities. Grier and Halliday propose an appropriate use of corticosteroids in severe bronchopulmonary dysplasia that may be life saving and that may also minimize adverse responses in the developing brain.¹⁰⁰

Infants receiving diuretics to treat chronic lung disease require periodic evaluation of their electrolyte status. Bumetanide may be associated with fewer electrolyte abnormalities, especially if dosing occurs on alternate days.⁹⁶  Furosemide therapy for chronic lung disease predisposes these infants to nephrocalcinosis. The PCP may need to screen patients for nephrocalcinosis by performing serial renal ultrasonography, by assessing calcium-to-creatinine ratios in the urine, or by examining the urine for erythrocytes (microscopic hematuria).

No current therapy effectively resolves nephrocalcinosis in preterm infants. Prevention may be the key. Furosemide should be used only when this diuretic is proven effective. When nephrocalcinosis is present, every attempt should be made to stop furosemide or other drugs that cause excessive urinary excretion of calcium. Nephrocalcinosis spontaneously resolved in many, but not all, infants in the first year of life. Other diuretics such as Aldactone and Diuril may be used as they are effect in controlling pulmonary edema secondary to bronchopulmonary dysplasia and they conserve or prevent lost of calcium in the urine.

Infants who have chronic lung disease may require more than 120-150 kcal/kg/d for weight gain because of their increased work of breathing.⁹⁸ Therefore, either breast milk with added fortifier or a formula with high energy density may be needed for nutritional support. Infants with chronic lung disease may also need restrictions in fluid intake, a therapeutic strategy that may further impair their growth. On occasion, infants with chronic lung disease may be discharged with home monitoring, which may include pulse oximetry for infants who have the most severe illness.

These infants are candidates for immunoglobulin therapy to prevent or ameliorate RSV infection (see Healthcare Maintenance of the NICU Graduate). Other pulmonary infections should also be managed with attentiveness and concern.

GI diseases

The 2 prominent intestinal problems encountered in premature infants discharged from the NICU are GER and complications arising from necrotizing enterocolitis (NEC). Reviews of GER^101,102 and NEC have recently been published.^103,104

GER can be suspected in premature and term infants who have repeated regurgitation or emesis after feedings, apnea after feedings, fussiness or painful crying during or after feedings, arching of the head and neck during or after feedings, a nasogastric or orogastric feeding tube, or rumination. Each of these signs or symptoms takes on additional importance  if the child's growth is poor.

GER has been associated with esophageal or duodenal atresia, diaphragmatic hernia, brain injury due to hypoxic-ischemic encephalopathy, prematurity whether chronic lung disease is present or absent, and many other neonatal conditions. Recent data have suggested that GER has no role in apnea of prematurity,¹⁰⁵ whereas an endoscopic study indicated that GER may be responsible for laryngeal edema, apnea, and bradycardia.¹⁰⁶

Testing to confirm GER has been the subject of contentious debate.⁴³ Diagnostic tests for GER include contrast-enhanced studies of the esophagus and upper GI tract, radiolabeled scanning after feedings, monitoring of esophageal pH (optimally done with dual high and low probes), and esophagoscopy with or without biopsy. Before a reliable pH probe test can be performed, medications that raise gastric pH must be withdrawn for several days (eg, 2-4 days). In the ideal situation, the patient's gastric pH should be known before a pH probe examination is performed. Some pediatric gastroenterologists recommend adding hydrochloric acid to the feedings during pH probe testing to avoid false-negative results due to high gastric pH.

The success rate of medical therapy for GER is less than ideal. Treatment may include prokinetic agents (eg, metoclopramide, erythromycin which have not proven effective in GER treatment), H2-receptor blockers or proton-pump inhibitors, thickened feedings, and positioning to facilitate gastric emptying. A study indicated that GER was worst when preterm infants were treated with metoclopramide. Data suggest that erythromycin 1.5-2.5 mg/kg given every 6 hours may effectively treat GER in some preterm infants.^107,108 However, reports suggest that erythromycin therapy increases the risk of hypertrophic pyloric stenosis. Erythromycin-induced hypertrophic pyloric stenosis may be more frequent when the antibiotic is intravenously administered at therapeutic doses rather than at the low oral doses used to treat GER. Therefore, if erythromycin is used to treat GER, the PCP should watch for symptoms associated with hypertrophic pyloric stenosis.

Thickened feedings and positioning have had mixed success in treating GER in neonatal clinical trials. Thickened feedings effectively decrease GER;^109,110 therefore, a resurgence in their use has occurred. Although GER may be a life-long problem in some infants (eg, term infants with profound brain injury due to hypoxic-ischemic encephalopathy), premature infants generally have self-limited disease that improves as the gastroesophageal sphincter and gastroduodenal motility matures. Infants with severe GER associated with hypoxic-ischemic encephalopathy may be candidates for treatment with gastric fundoplication. A pediatric gastroenterologist should collaborate with the PCP in caring for infants with severe GER.

For graduates of the NICU who have had NEC, the PCP must be alert for later problems. Complications of NEC include a need for ostomy care, malabsorption, intestinal dysmotility, a need for parenteral nutrition despite enteral feedings, cholestasis, infections of the ascending biliary tract, biliary calculi, late partial or complete bowel obstruction, and short bowel syndrome.

The prognosis of patients with short bowel syndrome is guarded,¹¹¹ and the PCP must follow up with these infants, as should a pediatric gastroenterologist and surgeon. Some of these complications may be present at discharge from the NICU, and some require continued surveillance. Poor growth is a frequent outcome. Dumping syndrome is observed in infants with ostomies or severe diarrhea during GI infections (eg, those due to rotavirus). Dumping syndrome may cause rapid dehydration and electrolyte imbalance. Strong evidence suggests that NEC is associated with increased occurrence of adverse neurologic outcomes.^112,113

The PCP must be diligent in recognizing growth failure, fluid imbalance, and electrolyte abnormalities in infants with GI disease. Scarring after neonatal GI surgery can cause partial or complete bowel obstruction after discharge. Repeated emesis, particularly if it is bilious, and/or a sudden onset of abdominal distension must always be investigated. Polymicrobial sepsis may be another indicator of partial or complete bowel obstruction after NEC or GI malformations.

When short bowel syndrome necessitates parenteral nutrition at home, catheter or gut-related bacteremia is a major risk factor and must be suspected, even if the patient has only subtle signs of infection (eg, irritability, low-grade fever, apnea). A pediatric gastroenterologist should monitor infants who have clinically significant complications secondary to NEC and other GI diseases. In particular, short bowel syndrome occurs in ELBW infants as a complication of NEC and has a high mortality rate.¹¹⁴ These infants have complex conditions and require management at a major pediatric gastroenterology or transplant center.

CNS disorders

The most common and serious CNS disorders that may be present in premature infants at the time of discharge are posthemorrhagic hydrocephalus, postmeningitic hydrocephalus, periventricular leukomalacia (PVL), and seizures. These disorders place the NICU graduate at high risk for poor long-term neurologic outcomes. Infants with these problems should be followed up in the NICU follow-up clinic. The discussion below is limited to CNS complications that most commonly affect infants born prematurely. Other common conditions affecting the CNS of NICU graduates include developmental defects in the brain and/or spinal cord. These conditions are discussed in other articles in the eMedicine journal.

Despite past beliefs, ELBW preterm infants with grade I subependymal or II intraventricular hemorrhage may have poor neurodevelopmental outcomes.^115,116 Grade III intraventricular or grade IV intracortical hemorrhage is associated with the least favorable neurodevelopmental results, but the degree of prematurity and the presence of chorioamnionitis may also be major contributors to severe long-term disabilities. Intraventricular hemorrhage may lead to posthemorrhagic hydrocephalus. In turn, intracortical hemorrhage causes cerebral infarction and may culminate in cerebral or cerebellar porencephaly. Porencephaly and posthemorrhagic hydrocephalus are among the most devastating CNS events in premature infants.¹¹⁷

The risk of these conditions is inversely proportional to gestational age. For example, 35% of infants with birth weights of 500-600 g have severe intracranial hemorrhage.³⁷ If posthemorrhagic ventricular dilatation occurs after intraventricular hemorrhage does, it is usually apparent on cranial ultrasonography within 2-3 weeks. Hemorrhagic cerebral events are occasionally observed in term neonates. Such hemorrhage in term infants carries an ominous prognosis. Infants who have had intracranial hemorrhage must always be monitored in neurodevelopmental follow-up clinics. They should also be referred to community services because rehabilitation is frequently necessary.

Although ventricular dilitation may be reversible, infants with severe intraventricular hemorrhage with posthemorrhagic ventricular enlargement are at high risk for neurodevelopmental handicap.¹¹⁸  The PCP must be informed of this clinical scenario. Rapidly progressive posthemorrhagic hydrocephalus may require permanent placement of a cerebrospinal fluid (CSF) shunt.¹¹⁹ The long-term neurodevelopment of ELBW infants who require shunt insertion is very unfavorable compared with ELBW infants with intraventricular hemorrhage who do not have ventricular enlargement.¹²⁰  

If a ventriculoperitoneal shunt is needed, the PCP must monitor the NICU graduate for shunt infections or malfunctions. Malfunctions are typically due to an occlusion of the proximal or distal cannula with a subsequent increase in intracranial pressure. Poor feeding, vomiting, irritability, lethargy, sleepiness, apnea, and seizures may be signs and symptoms of shunt blockage. If fever or a septic appearance is also present, the PCP also should suspect shunt infection and meningitis. The PCP should monitor the patient's head circumference for rapid or slow growth.

PVL is caused by an ischemic infarction of the white matter, most commonly adjacent to the lateral ventricles. PVL can be observed in either preterm or term infants. The pathogenesis of cerebral white matter injury in preterm infants has been reviewed.¹²¹  Antenatal or intrapartum hemorrhage and severe placental disease (eg, chorioamnionitis) have been associated with PVL.¹²² Postnatal sepsis or NEC are associated with white matter abnormalities on MRI at term gestation and adverse neurodevelopmental outcomes.¹²³  

Other postnatal events leading to PVL include CSF infections or intraventricular hemorrhage, life-threatening apnea and bradycardia, and cardiorespiratory arrest. The quality of general movements of preterm infants at age 3 months can often identify white matter pathology.¹²⁴  The condition is otherwise identified on cranial sonograms as echogenic areas in the periventricular white matter. Injuries in these areas evolve into cysts.¹²⁵  PVL is highly associated with subsequent neurodevelopmental disabilities, particularly cerebral palsy (motor dysfunction of infancy or spastic paresis). Persistence of cysts is known to increase the risk of severe neuromotor abnormalities. PVL is always a reason to schedule appointments in a neurodevelopmental follow-up clinic. Affected infants should also be referred to community services that provide early intervention and rehabilitation.

Preterm infants whose cranial sonograms show reduced growth of the corpus callosum during the patient's NICU stay are at increased risk for psychomotor delays and cerebral palsy.¹²⁶ Moreover, abnormal findings on MRIs obtained at term in very preterm infant are predictive of adverse neurologic outcomes at 2 years of age.¹²⁷ Some investigators believe that identification of neuroanatomic abnormalities on MRI can predict the need for early interventions.¹²⁸  The PCP should be advised about any imaging findings that suggest the possibility of an unfavorable neurodevelopmental outcome before the patient is discharged home, and the parents should be fully counseled about the findings. Whether this knowledge, when conferred to parents, enhances or diminishes parental involvement in their infant's rehabilitation is controversial.

A history of neonatal seizures is another finding associated with long-term psychomotor or neuromotor handicaps.¹²⁹ Reasons for neonatal seizures include hypoxic-ischemic injury, direct cerebral trauma, intracranial hemorrhage, metabolic abnormalities, malformations, and infections. Neurodevelopmental outcomes after neonatal seizures are clearly related to the etiology of the seizures. However, in some patients, a specific cause is never determined. When known, the cause may be predictive of the ease or difficulty with which the seizures can be controlled with anticonvulsants.  Phenobarbital is the mainstay of anticonvulsant therapy for neonatal seizures.¹³⁰ However, published proceedings of a neurology group on neonatal seizures have recommended that clinical trials be conducted to evaluate phenobarbital therapy.¹³¹  

The duration of treatment for neonatal seizures is controversial, partly because of concerns that anticonvulsants may hinder brain development. Among infants without signs and symptoms, and in the absence of electroencephalographically recorded seizures, pediatric neurologists may recommend discontinuing anticonvulsants before the patient's discharge or shortly thereafter. Before anticonvulsants are withdrawn, electroencephalography must be performed to exclude subclinical seizures. A neurologist should evaluate any NICU graduate who has persistent or difficult-to-control seizures. These infants should also be monitored in neurodevelopmental follow-up clinics and referred to appropriate community services.

A common neurologic condition associated with neonatal seizures is hypoxic-ischemic encephalopathy. Maternal intrapartum conditions that commonly result in profound hypoxic-ischemic encephalopathy include placental abruption, uterine rupture, and prolonged cord compression. Hypoxic-ischemic encephalopathy is a devastating event that most often affects term neonates. Survivors of hypoxic-ischemic encephalopathy have long-term sequelae more commonly than survivors of extreme prematurity. All neonates with Sarnat stages 2 (moderate) and 3 (severe) should be enrolled in follow-up programs.¹³² The PCP should be aware of whether the hypoxic-ischemic encephalopathy was treated with head or whole body cooling.¹³³

If infants have profound damage (often in association with a burst-suppression pattern on initial electroencephalography and an abnormal MRI finding), extensive home care and community services may be required. The PCP must monitor the patient for recurrence of seizures many months after anticonvulsants are discontinued. The PCP has the responsibility for coordinating the complex care infants with hypoxic-ischemic encephalopathy require.

Eye problems

Retinopathy of prematurity (ROP) is an important problem that the PCP must monitor. One of the most devastating complications of preterm birth is blindness secondary to ROP. This condition is complex in its pathophysiology. Certain clinical conditions, such as infections, increase the risk of ROP. Its association with oxygen therapy is long known, but this causal relationship is complex. One firmly established etiologic factor is the degree of prematurity. Therefore, the infants at highest risk are those who were born prematurely with an ELBW.

The AAP published guidelines for ROP screening.¹³ However, some neonatologists take a view more conservative than of the AAP and perform screening in large or relatively mature preterm infants, especially if they received prolonged oxygen therapy and/or assisted ventilation. A subspecialist trained to recognize neonatal retinal diseases must perform the screening for ROP. The subspecialist must continue to examine the patient and make recommendations for follow-up examination of the neonatal retina until it is fully vascularized. 

Complete vascularization usually occurs by 44-48 weeks after conception but occasionally takes longer than this time interval. Screening examinations are important because, if retinal detachment (ie, threshold disease) is a risk, the infant may be referred for laser therapy of the retina to prevent it. Recent studies from the United Kingdom have proposed more aggressive criteria for intervention when preterm infants have ROP.

Retinal detachment can also occur relatively late in life. Again, this is particularly common in premature ELBW infants. Preterm infants who have had evidence of ROP must also be screened for refractive disorders and for amblyopia at 6 months after discharge, at age 2-3 years, before they begin school, during grade school, and during adolescence when rapid growth of the ocular globe is occurring. Infants with a history of ROP are at increased risk for myopia. In later life, glaucoma may also be more common in preterm infants than in their term counterparts. When a PCP examines premature infants younger than 1 year, the PCP must assess the baby for strabismus.

Hearing problems

The incidence of hearing loss increases in NICU graduates compared with the general population of well neonates. Many factors can contribute to such hearing loss, including hypoxia, certain drugs used alone or in combination, and infections. Silent congenital, symptomatic congenital, or postnatally acquired cytomegaloviral (CMV) infection is highly associated with hearing loss in later life. The hearing loss caused by CMV infection may progress over time. Most intensive care units in the United States use only CMV-seronegative blood for RBC transfusions. This practice has lowered the incidence of acquired postnatal CMV infection among hospitalized neonates, but infants might still be infected with CMV from platelet or plasma-derived blood products.

All NICU graduates must undergo a hearing evaluation before leaving the hospital. A number of devices are now available for this purpose. The PCP should be informed at discharge whether the patient passed the hearing screen. If the infant did not, he or she must be referred to an audiologist who practices with a pediatric otolaryngology specialist.

Developmental Follow-Up: General Concepts

Methodologic problems in follow-up studies have produced conflicting data about the sequelae of being born early.¹³⁵ As the total number of survivors at potential risk for neurodevelopmental morbidity increases, many clinical research questions with major ramifications on medical care have evolved. These questions can be answered only by performing long-term follow-up studies.¹³⁶

Although neurodevelopmental outcomes are increasingly used to determine the efficacy of medical interventions in infants born preterm, long-term follow-up studies are infrequently performed because of cost and subject dropout. The bias of neurodevelopmental data is that they are not as precise as radiographic or biologic measurements. In addition, confusion occurs because of (1) the frequent disconnections between adverse perinatal experiences and later outcomes, (2) the moderator and mediator effects of socioeconomic status and other environmental influences, and (3) the long time lag necessary to complete longitudinal assessments.^137,134

Besides initial biologic risks, perinatal interventions designed to address these risks may substantially affect later development. Therefore, extended follow-up is critical to identify possible negative effects that a medical intervention or the standard of care might have on the child’s brain that might not be obvious in the first years of life. This point was clearly demonstrated in the use of postnatal steroids to treat chronic lung disease and in late visual impairment and developmental delays with the use of oxygen.^138,139 Of interest, standardized guidelines about follow-up services for high-risk infants in tertiary care centers are lacking despite the requirement for approved neonatal fellowship training programs to include experience in follow-up clinics and the increasing number of centers involved in networks.

Areas of concern include social issues and neurologic, cognitive, behavioral, physical, health-related quality-of-life, and functional outcomes. This discussion is restricted to cognitive and neuropsychological outcomes, which are sometimes considered neurodevelopmental. Outcome studies have primarily emphasized the incidence of major disabilities such as moderate-to-severe mental retardation, sensorineural effects (eg, hearing loss, blindness), cerebral palsy, and epilepsy. Babies born with low birth weight (LBW), less than 2500 g, have a 6-8% incidence of developing these major disabilities.

Those born at very low birth weight (VLBW), less than 1500 g, have a 14%-17% incidence; whereas extremely low birth weight (ELBW) infants, less than 1000 g, have a 20-25% rate. Therefore, as birth weights decline, disabilities increase.^140,141 In comparison, major disabilities occur in 5% of infants born full term. These rates have remained relatively constant over the last decade.

The situation is complex because the parents' social, ethnic, and educational backgrounds may also influence the prevalence of these disabilities. In addition, though major disabilities are often identified during infancy, high-prevalence and low-severity dysfunctions become most obvious as the child reaches school age. Further compounding the issue is that no good predictors of these subtle problems can be identified during infancy or preschool age.

Early in infancy, whether problems are transient and result from continuing recovery or catch-up from the negative effects of preterm birth or whether they reflect the emergence of a permanent handicap is extremely difficult to determine. Many functional outcomes cannot be adequately gauged until the child encounters broad, complex demands and situations that require developmentally complex functions. Preexisting deficits in these functions become apparent only when they are challenged directly.¹³⁷ This situation again substantiates the necessity of longitudinal follow-up.

Developmental Follow-Up: Specific Strategies

Follow-up protocols vary in terms of patients who should be followed up, levels and frequencies of follow-up, and testing and outcomes.

Patients Who Require Follow-up

Clinicians should consider birth weight and gestational age when determining who should be followed up. Gestational groups are divided into less than 28 weeks' gestation (extremely premature), 28-32 weeks' gestation (very premature), or 33-36 weeks' gestation (premature). Consideration of birth weight alone may result in the inclusion of infants who are relatively mature but whose growth was restricted because of an adverse intrauterine environment. Also, use of birth weight alone may bias evaluations or biomedical findings because conditions such as periventricular leukomalacia (PVL) are relatively infrequent in growth-restricted fetuses.

Extremely low birth weight (ELBW) infants need follow-up assessments because they are subject to 2-hit CNS involvement. The CNS of the at-risk infant is potentially subject to developmental disruption, insult, or both. Premature birth changes the spatial and temporal progression of brain structures (eg, migration, organization and differentiation, myelination) and alters brain architecture and connectivity. Also compounding the disrupted brain development are altered postnatal visual, auditory, tactile, and vestibular-proprioceptive experiences. The CNS of high-risk fetuses and neonates are frequently subject to second insults, such as maternal infections, hypoxic-ischemic encephalopathy, intraventricular hemorrhage, or PVL. Extreme prematurity (weight <1000 g or age 28 wk or younger), regardless of other factors, increases the risk of CNS insults, including grade III or IV intraventricular hemorrhage, PVL, and seizures.

Risk criteria differ depending on whether the infant was born preterm or at full term. Moreover, medical conditions can exacerbate the risk; examples of such conditions are extracranial or intracranial trauma, respiratory disorders, infections, birth weight, young gestational age, hyperbilirubinemia that requires exchange transfusion, encephalopathy, fetal growth restriction, and other complex medical problems. Likewise, interventions to deal with specific disease states (eg, resuscitation, prolonged ventilation, postnatal steroids, total parenteral nutrition) can also raise the risk. Also contributory are social and/or environmental risks; these often occur in conjunction with biologic risks and place infants at double jeopardy.¹⁴⁷

Levels of Follow-up

As indicated in the National Institute of Child and Human Development–National Institute of Neurological Disorders and Stroke (NINDS) workshop,¹³⁶ levels of follow-up differ. Level I could consist of a telephone interview from a designated neonatal ICU (NICU) staff member or use of a screening instrument such as the Cognitive Adaptive Test and Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS))¹⁴⁸ or the Ages and Stages Questionnaire.¹⁴⁹ Subsequent referrals could be made as needed. Level II could involve a clinic visit with the use of one of the aforementioned screening instruments or a hands-on test, such as the Bayley Infant Neurodevelopmental Screener (BINS).¹⁵⁰ Additional allied professionals, such as a dietitian and physical, occupational, and speech therapists, may or may not also evaluate the child. Level III can entail comprehensive serial assessments by a multidisciplinary team.

Frequency of Follow-up

The frequency of follow-up contact is superimposed on the level. Patients at high risk or those in whom neurodevelopmental problems have already been identified should be evaluated soon after discharge from the NICU and frequently thereafter. In general, serial contact is recommended whether follow-up is for surveillance (eg, quality assurance) or for research purposes and regardless of the level of follow-up.

The frequency of follow-up involves 2 issues: the optimal ages for assessment and the intensity or level of follow-up, which also depends on constraints such as cost, personnel, and/or unique characteristics of the center. Some have found that beginning follow-up visits shortly after discharge enhances the likelihood the family will continue with subsequent visits.

Corrected age 6 months

Evaluation at age 6 months offers a window during which indicators of severe handicaps can be identified. An evaluation at this time also provides early contact with the family, enhancing continuity of contact and helping to ensure that children are involved in early intervention services.

Conversely, the influence of many medical and/or biologic issues is decreasing. In the converse, recovery from medical procedures, feeding difficulties, and subsequent hospitalizations and procedures may still affect neurodevelopmental assessments. Tone, neurosensory (eg, auditory, visual) functions, gross and fine motor coordination, early verbal skills, interactive capacities, and some cognitive processes can be evaluated. Use of assessment before this age is questionable. Screening with tests such as the BINS may be sufficient, but this approach again underscores the interplay between the frequency and level of follow-up.

Corrected age 12 months

Environmental factors do not exert a major influence at this age, and biomedical issues, such as oxygen supplementation for chronic lung disease, tend to resolve and lose their effect on testing. By 12 months corrected age, a varied behavioral repertoire is emerging, and cognitive processes and developing language skills can be assessed. However, at this age, cognitive and motor functions are still highly intertwined, and this period of developmental acquisition is a time of variability as well. Some neurologic abnormalities identified in the first year of life are now transient or improving. In the converse, findings in some infants worsen over time.

Corrected age 18-24 months

By 18-24 months, environmental factors exert increasing influences on evaluation results. Cognitive and motor abilities diverge, language and reasoning skills develop, and the ability to predict early school performance improves. However, many intelligence tests have weak floors at this age, restricting assessment to only developmental tests. As a result, impairments may be underestimated. Test refusals may invalidate results or produce false-positive results. Judging performance at 2 years on the basis of corrected age (chronologic age minus weeks born prematurely) rather than actual age is controversial but generally accepted. Standard follow-up protocols in many multicenter networks specify how the age at evaluation is calculated.

Corrected age 3-4 years

Intelligence can first be assessed at 3-4 years. Intelligence includes concept development, pre-academic readiness skills, early indicators of executive function and attention, and abilities in visual-motor integration. Verbal and nonverbal skills can be differentiated. Moreover, the predictability of later intelligent quotient (IQ) on the basis of scores at this age is acceptable. Environment and social support, as well as other factors, broadly influence test results most strongly from this age onward.

Age 6 years

By age 6 years, additional tests and procedures can be used to access attention problems, academic skills (at approximately the first-grade level), socialization, and neuropsychological functions. The selection of possible tests that can be used is more limited at age 5 years than at age 6 years.

Age 8 years

Intelligence, neuropsychological functions, learning disabilities, school performance, and social and behavioral adjustment can be adequately assessed by age 8 years (approximately the third grade in school). The predictive validity of IQ scores is highest now compared with earlier ages.

Summary of the frequency of evaluation

Evaluation after age 3-4 years is often not feasible in many follow-up programs whose main focus is surveillance. This is when the primary care physician (PCP) should monitor the child's school performance and periodically review developmental, cognitive, academic, and behavioral concerns.

A hybrid, parallel model is used at the authors' institution. In a developmental continuity clinic, infants at greatest biologic risk (eg, 1250 g or less or 28 weeks' gestation or younger) or those undergoing clinically significant interventions (eg, for intraventricular hemorrhage, asphyxia, prolonged mechanical ventilation, necrotizing enterocolitis [NEC], retinopathy of prematurity [ROP]) are examined at age 6 months, 12 months, 24 months, and 36 months (with the first 3 ages corrected for prematurity). At the first 3 appointments, the BINS instrument is applied, occupational-physical and speech-language evaluations are made, and medical examination is performed. At age 36 months, detailed developmental or cognitive evaluation substitutes for the BINS (ie, Bayley Scales of Infant and Toddler Development). The developmental continuity clinic serves both surveillance and research functions.

Children treated in the author's NICU who do not meet the predetermined level of risk are seen by nurses in the regular, serial follow-up clinic and screened using the BINS. This clinic has a lowered level of intensity. However, if concerns are identified during screening, the children are referred for early intervention services and for inclusion in the intensive, parallel developmental continuity clinic for ongoing assessment. In both clinics, the PCP receives written communication about the findings and the appropriate strategies for rehabilitation.

Individual program staff must decide on the possible combinations of levels and frequency of follow-up, which depend on the needs and the constraints of a given NICU.

Testing and Outcomes of NICU Graduates

In addition to obvious moderate-to-severe disabilities, other suboptimal outcomes can occur in high-risk infants. These include motor and neurologic deficits, reduced intelligence, learning disorders, language difficulties, visuomotor problems, impaired executive function, and attention deficit hyperactivity disorder (ADHD).

Motor and neurologic deficits

Motor and neurologic outcomes are major concerns when they arise as a high-risk infant matures. Different risk factors may affect these outcomes.^136,151 The link between perinatal problems and deficits in these areas also appears to be relatively direct. The incidence of dystonia in preterm infants peaks at 7 months corrected age, with a prevalence of 21-36%.^152,153

Noteworthy is the fact that children with dystonia have an increased risk of later cognitive and motor problems. Often recognized are neurologic soft signs (eg, motor, sensory, or integrative functions but not localized brain dysfunctions). These deficits increase the risk of subnormal IQ or learning disabilities (particularly reading) in children with normal IQs. Upper-extremity motor tasks involving visually guided ballistic arm movements (eg, bouncing, catching, throwing) are particularly affected.¹⁵⁴ The purported mechanism is that parallel "mental" dysfunction involves circuits in the neighborhood of motor tracts that also sustain damage, but these abnormalities are not apparent until later in life. Motor injury is more self-correcting, whereas cognitive abnormalities are not.

Learning disorders

More than one half of all former very low birth weight (VLBW) infants and 60-70% of ELBW infants require special assistance in school. By middle school, ELBW infants are 3-5 times more likely than those born at term to have a learning problem in reading, spelling, writing, or mathematics, with mathematics and broad reading most disrupted.^157,146 Approximately 16-20% of children born with a birth weight less than 1500 g repeat a grade, and 20% are taught in self-contained classrooms for students with learning disabilities. Almost one third are in mainstream classrooms, but these children are functioning more than 1 grade below their placement.¹⁴⁶ Many children born prematurely later develop nonverbal learning disabilities.¹⁵⁸ Environment, gender, and heredity also have moderating effects, and learning disorders are likely related to both medical-biologic and environmental risks. The prevalence of learning disorders appears to increase 4-fold in children born at risk.¹³⁷

Language difficulties

For LBW infants, many language functions are in the average range, particularly vocabulary, receptive language, verbal fluency, and memory for prose. In the converse, relatively complex and subtle verbal processes or measures, such as understanding syntax, abstract verbal skills, verb production, mean length of utterance, auditory discrimination, difficulty following complex instructions, organization, and language processing and reasoning are deficient in preterm versus term infants.^159,160 Deficits in verbal working memory may also be present.

Functional MRI and event-related potentials studies indicate differences in the way auditory and language functions are carried out in patients born prematurely.^161,162

Language is also susceptible to negative environmental influences.

Visuomotor problems

Most VLBW and ELBW babies manifest later visuomotor problems.^163,164 Copying, perceptual matching, spatial processing, finger tapping, pegboard performance, visual memory, spatial organization and visuosequential memory, and handwriting speed and legibility are affected.^165,166,167 Many of these preterm patients are left handed, and their probability of needing glasses is 3-fold greater than that of healthy full-term infants.

Impaired executive function

Executive function is a broad term that refers to coordination of many interrelated processes. It involves purposeful, goal-directed behavior that is instrumental to cognitive, behavioral and social functions. Problems in executive function are reported in children born prematurely, especially if they have white matter pathology.^168,164,169 Preterm infants reportedly have increased difficulty in starting activities, displaying flexibility in generating ideas and strategies for problem solving, holding information in short-term or working memory, planning a sequence of actions, and organizing information. These deficits appear to be in the so-called "cool" metacognitive processes compared with the "hot", behavioral regulation of executive functions (ie, inhibition, shifts in emotional control).

Attention deficit hyperactivity disorder

Interest in the incidence of autism spectrum disorders (ASDs) in very preterm infants is increasing. In a study from Limperopoulis et al, 20% of 91 toddlers who were born VLBW infants had positive results on the Modified Checklist for Autism in Infants and Toddlers (M-CHAT).¹⁷³  Although the M-CHAT does not diagnose an ASD, positive findings raise concerns.

Schendel and Bhasin report data from a longitudinal surveillance study that indicate a 2-3 fold increase in ASDs in infants born as either LBW or preterm infants compared with peers.¹⁷⁴  An increased tendency was observed toward ASD and mental retardation, intellectual disability, and/or developmental disability compared with ASD alone. Moster et al  used data from the National Registries of Norway and followed more than 900,000 individuals into adulthood.¹⁷⁵  These investigators reported an odds ratio (OR) of 9.7 for ASD in those born at 23-27 weeks' gestation, and 7.3 for those born at a postconceptual age of 28-30 weeks. Therefore, the prevalence of ASD in those born prematurely is 2-3 times greater than in the general population and perhaps 7-9 times greater in ELBW infants. ASD in these children may be more severe and may be accompanied by other disabilities compared with higher functioning ASD that occurs in isolation. This trend underscores the need for ASD screening at the 18-24 month NICU follow-up visit.

Late preterm infants

Another area of increased interest involves infants born in the late preterm range (32-34 weeks' gestation and older [ie, <37 weeks' gestation or term]). In the last 6-8 weeks of gestation, a 35% increase in brain size and a 5-fold increase in white matter volume occurs. Neuronal connectivity, dendritic arborization, synaptic junction formation, and maturation of neurochemical and enzymatic processes occur.¹⁷⁶  Chyi et al reported that late preterm (LPT) infants had lower reading and math scores than their term counterparts in kindergarten and first grade and lower teacher ratings of reading from kindergarten through fifth grade.¹⁷⁷  The likelihood of special education involvement was 1.4-2.1 higher. Huddy et al  reported that one-third of their sample of children born at 32-35 weeks' gestation had special education needs,¹⁷⁸ whereas Moster et al documented a risk ratio (RR) of 1.6 for mental retardation/intellectual disability and 1.5 for psychologic, developmental, or emotional disorders in late preterm infants.¹⁷⁵  These data suggest that late preterm infants have an incidence of sequelae that falls on a continuum between those born at younger gestational ages and those born at term. A selection process for late preterm infants that has high predictive accuracy for neurodevelopmental delays or school problems is not currently available.

Areas of Assessment and Assessment Tools

Proper assessment is critical to evaluate the aforementioned areas of function that are associated an increased probability of problems. In both research and clinical surveillance programs, the ideal situation is to extend assessment beyond traditional intelligence quotient (IQ) and achievement testing. Global scores may not help in identifying subtle problems that can interfere with a child’s learning and development.
 
Tests or rating scales should be directed at measuring the following areas that are likely to be deficient:^142,136

• Intelligence, including verbal and nonverbal function
• Achievement
• Attention and executive functions - Planning, organization, monitoring, inhibition, working memory
• Language - Phonologic awareness, syntax, verbal fluency, comprehension of instructions, high-order abstracting functions)
• Sensorimotor functions - Visuomotor precision, fine motor speed
• Visuospatial processes - Design copying, visual closure, visuospatial planning, handwriting
• Memory and learning - List learning, delayed recall, narrative memory, assessment of semantic and strategic and rote and episodic verbal and visual functions
• Behavioral adjustment - Attention deficit hyperactivity disorder (ADHD), internalizing and externalizing problems
• Functional status - Self-care, mobility, communication

Detailed evaluation obviously raises costs, which may be difficult to justify and therefore unfeasible in many clinical or research settings. A compromise is to use representative tests to measure areas of function that are likely to be problematic in children born prematurely or to assess certain functions at different times.

Options for comprehensive cognitive-assessment protocol are as follows:¹³⁶

• Age 6 months, 12 months, and 13-24 months
  • Bayley Scales of Infant Development, 2nd edition - Mental Development Index and Psychomotor Development Index
  • Bayley Scales of Infant Development, 3rd edition - Cognitive language, motor, social-emotional, and adaptive
• Age 3-4 years
  • Differential Ability Scales
  • Bayley Scales of Infant Development, 2nd or 3rd edition (at 3 y)
  • Stanford-Binet Intelligence Scales, 5th edition
  • Wechsler Preschool and Primary Scale of Intelligence, 3rd edition
  • McCarthy scales
  • Bracken Basic Concept Scale-Revised
  • Kaufman Assessment Battery for Children, 2nd edition
  • Behavior Rating Inventory of Executive Function
• Age 6 years
  • Wechsler Abbreviated Scale of Intelligence
  • Stanford-Binet Intelligence Scales, 5th edition
  • Wechsler Intelligence Scale for Children, 4th edition
  • Developmental Test of Visual-Motor Integration
  • Developmental Neuropsychological Assessment
  • Continuous Performance Test
  • Behavior Rating Inventory of Executive Function
  • Rating scale - Kaufman Assessment Battery for Children, 2nd edition
• Age 8 years
  • Wechsler Intelligence Scale for Children, 4th edition
  • Wechsler Abbreviated Scale of Intelligence
  • Stanford-Binet Intelligence Scales, 5th edition
  • Developmental Neuropsychological Assessment
  • Behavior Rating Inventory of Executive Function
  • Continuous Performance Test
  • Rating scales - Wide Range Assessment of Memory and Learning, 2nd edition; Children’s Memory Scale; California Verbal Learning Test-Children’s Version

The protocols can be altered in frequency, areas assessed, depth of evaluation, and evaluation instruments. Examiners should select specific tests from these lists, tailoring the protocol to the follow-up program of the particular patient. Scaled-down cognitive-neuropyschological protocols are as follows:¹³⁶

• Age 6 months, 12 months, and 18-24 months
  • Bayley Infant Neurodevelopmental Screener
  • Ages and Stages questionnaire
  • Cognitive Adaptive Test and Clinical Linguistic and Auditory Milestone Scale
  • Bayley Scales of Infant and Toddler Development Screener, 3rd edition
• Age 3-4 years
  • Kaufman Brief Intelligence Test, 2nd edition
  • Stanford-Binet Intelligence Scales, 5th edition, Abbreviated Battery IQ
  • Kaufman Assessment Battery for Children, Short Form
  • Developmental Test of Visual-Motor Integration
• Age 6 years
  • Wechsler Abbreviated Scale of Intelligence
  • Stanford-Binet Intelligence Scales, 5th edition, Abbreviated Battery IQ
  • Kaufman Brief Intelligence Test, 2nd edition
  • Wechsler Intelligence Scale for Children, 4th edition
  • Continuous Performance Test
  • Developmental Test of Visual-Motor Integration
• Age 8 years
  • Wechsler Abbreviated Scale of Intelligence
  • Stanford-Binet Intelligence Scales, 5th edition, Abbreviated Battery
  • Kaufman Brief Intelligence Test, 2nd edition
  • Developmental Neuropsychological Assessment, selected subtests
  • Continuous Performance Test
  • Developmental Test of Visual-Motor Integration

In summary, developmental follow-up is a critical component of the overall care of high-risk infants. Numerous options are available in terms of level, frequency, and patient age at the time of assessment. Follow-up of high-risk infants can be undertaken for surveillance, research, or both. However, serial evaluation is necessary because of rapid developmental changes during infancy, silent periods, and increasing environmental and educational demands that may uncover previously unidentified deficits. Medical status and quality of life should also be monitored. The child’s family and the primary care physician (PCP) should be active partners in this entire process.

Counseling Caregivers During and After the NICU Stay

General concepts

Whether they are dealing with extreme prematurity or serious malformations, parents of high-risk neonates typically ask 2 basic questions during counseling: "Will my baby survive?" and "Will my baby be normal?" These questions cannot be easily addressed, and the answers depend on circumstances of the individual infant. Therefore, answers may need to be given in general terms, which can be frustrating for parents. These questions may arise again during the infant's hospital stay, although parents may be reluctant to ask them again because of their fears about the potential answers.

When an infant arrives in the neonatal ICU (NICU), or in the office during follow-up visits, another important question is, “Is my baby gaining weight or growing?” Parents often reduce their fear and apprehension to these simple terms. The psychological trauma parents experience when their infant is hospitalized in the NICU cannot be underestimated.^183,184

One of the most difficult and perhaps most overlooked aspects of care of the high-risk neonate is effective, timely, and compassionate delivery of information to parents and family members by the medical staff involved. Although most members of the medical team are well prepared to meet the physiologic and medical needs of the infants they care for, the psychological, emotional, and spiritual needs of the family members can be ineffectually met when concern is directed primarily toward the infant.

The goal of communication is to provide information to all who need it in an efficient and compassionate manner. Parents are often the first people to whom a change in the patient's status and in future plans should be directed, but others may also require this information. Social service agencies, state and federal agencies, and pastoral support staff may also require timely updates according to the desires of the particular parents.

To effectively counsel parents of high-risk neonates requires, caregivers should identify the specific needs of the family early in the infant’s hospitalization. Also, members of the medical team should be aware of their individual skills and responsibilities in interacting with parents and extended family members.

A helpful approach is to plan a visit occurring immediately before or soon after discharge to ascertain the parent’s expectations regarding their child's outcome and follow-up care. As risk factors for later problems are identified, they must immediately be explained to parents and other care providers in a manner that is understandable and complete. Healthcare providers be able to collaborate with parents who may feel isolated and who be in various stages of grieving.

By suggesting support services or parental support groups, providers may assist parents in coping with the stresses of uncertainty regarding their individual situation and their child's anticipated outcomes. Programs for social service contacts, developmental disability services, home nursing, and economic assistance are addressed in Resources for Parents and Healthcare Professionals.¹⁸⁵

By the time of discharge, the staff should have established the parent’s understanding about their infant’s status and potential outcome. Medical conditions that require close follow-up should be identified and communicated, and care plans should be developed, as noted in Discharge Planning. Providers must understand and accept cultural diversity in childcare, and skilled medical interpreters should be available when necessary. Each medical provider must listen carefully to the parents’ questions to answer them as well as any implied questions.

The medical team can anticipate that parents will have new questions regarding their child’s potential outcome and abilities at subsequent visits. Goals of medical and other professionals should be to explain previous problems and risks in relation to current physical and developmental findings. Avoiding medical jargon and using language appropriate to each parent’s level of understanding is important. For example, early use of the term cerebral palsy to explain motor dysfunction of infancy or spastic paresis desensitizes parents to it and may open avenues of explanation regarding neurologic dysfunction and therapeutic intervention. The phrase "out of the normal range" must often be carefully explained. Although the phrase may be distressing to parents, its use may allow an infant to qualify for interventional services earlier than otherwise possible.

Providers must often explain the difference between medical and parental responsibilities. Initial counseling should be directed at the importance of maintaining the discharge plans, including preventive healthcare. Routine healthcare, including immunizations and safety counseling, should be addressed at each visit. The need for respiratory syncytial virus (RSV) prophylaxis and influenza vaccination may be important points of discussion for infants with chronic lung disease.

Regular multidisciplinary neurodevelopmental evaluation must be reinforced, as well as the necessity for preplanned or future referrals to medical specialists. The potential need for periodic or regular evaluations by gastroenterologists, nutritionists, neurologists, rehabilitation specialists, orthopedic surgeons, physical therapists, occupational therapists, and speech therapists should be introduced in the discussions about outcome. In the process of discharge planning and follow-up, providers should stress the uncertainty of outcomes for specific neurologic risks in the extremely low birth weight (ELBW) infant. The propensity for later dysfunction should be discussed, even if an infant appears to be doing well during early follow-up.^140,186

Although the relative statistical risks associated with some of the previously described conditions should be discussed, clinicians must carefully explain that definitive medical diagnoses can be appreciated only over an extended period.

Physicians must be candid in discussing abnormalities found on examinations in the NICU or during early follow-up visits, especially if they increase the risk of an adverse outcome. Providers may want to avoid sharing this information because it creates sadness and anger in the parents and other caregivers. Nevertheless, the provider must undertake this task because the parents may later claim that they were never told our infant was affected or at risk. Avoiding the truth about potential neuromotor and psychomotor disabilities may destroy the relationship and future collaboration between providers and caregivers. Honesty regarding an unfavorable outcome also enables parents and other caregivers to understand what interventions and therapeutic plans are needed.

The counseling process is often complicated because of denial of the apparent facts by the parents and family members. Although honesty regarding anticipated outcomes is always wise, stressing that many high-risk situations change in ways that are not initially evident is prudent. Unrealistic parental hopes can be gently addressed and should not be ridiculed or disparaged. The authors emphasize that a stable and consistent home environment almost always improves the infant's outcomes. Guilt over a poor neuromotor and/or psychomotor outcome in an ELBW infant or an infant with a malformation syndrome that requires complex medical care can result in serious discord in the family. The provider must always be aware of this potential situation and be ready to intervene with counseling. Disruption of the family unit only potentiates unfavorable outcomes for the infant or child.

Asking parents what they want or expect, particularly early in the evaluation, is unwise. Rather, suggest to parents that, in the opinion of the multidisciplinary team, certain adverse physical or developmental outcomes might be anticipated and that therapies will be recommended if these outcomes occur. Asking parents what they feel about such outcomes and plans opens communication and helps them participate, even if they do not completely understand what is being discussed.

Each family unit eventually decides on the degree to which they wish to participate in the healthcare of their child. As parents learn about their child’s condition and take on advocacy roles, they may become active participants. However, some parents are never able or willing to actively participate in planning. Caution should be taken to avoid making parents feel guilty about too much, or too little, intervention.

As parents find healthcare providers with whom they can communicate, that individual may assume the role of coordinator of care.²⁷ Information must flow between this person and other providers. In the ideal situation, this individual is a primary care physician (PCP) but is often another healthcare professional participating in the child's care. A primary coordinator with whom parents can feel comfortable should be identified as the team leader because such a person facilitates parent-staff and interdisciplinary communication.

Seamless communication between public and private agencies, as well as parents and physicians, helps prevent duplication of services and provides parents the emotional and medical support that they require for the optimal care of their child. In some cases, the parent may become the best care coordinator for their child. If this situation occurs, they must be accepted as an active participant in the healthcare team.

Healthcare providers who are unwilling to allow active participation of informed parents in their child’s care create a difficult environment for continuing and optimizing care. Indeed, providers must always remember that the major goal of both parents and providers is to achieve the best outcome for the patients and families. With regard to keeping the family intact, the risk of divorce may increase among parents of NICU graduates, and the PCP should be alert for signs of family stress.¹⁸⁷

Specific recommendations

Today, counseling of parents often begins before birth.¹⁸⁸ The availability of prenatal biochemical screening tests, improved knowledge of genetic diseases and family histories, and the use of fetal ultrasonography have made the recognition and management of maternal and/or fetal disease more commonplace now than ever before.

Depending on the specific problems, counseling may entail one or more prenatal conferences with obstetricians, perinatologists, geneticists, surgical subspecialists, neonatologists, and the infant’s and family’s PCPs. The PCP should be kept informed about these consultations. These conferences should continue throughout the patient's NICU stay and during visits to the PCP’s office. Parents or caregivers must actively participate in decision-making. Many studies indicate that parental contribution to the physical and psychomotor welfare of their NICU graduate is the most important factor for a favorable long-term outcome.¹⁸⁹

The Internet has become an important source of information to find institutions that provide specialized care for NICU graduates. Care facilities are often near the family’s home. To identify local or national support groups, parents of infants with extreme prematurity, unusual or complex malformations, or rare metabolic diseases can consult social workers, PCPs, Web-based resources, and special agencies (eg, the March of Dimes). The PCP should take a proactive role in helping parents connect with other parents in similar situations.

The Vulnerable Child

An interesting and perplexing management problem in the follow-up of high-risk neonates is vulnerable child syndrome. In 1964, Morris Green, MD, described this syndrome.¹⁹⁰ Green summarized its nature in 1986.¹⁹¹ In brief, NICU graduates, especially those born prematurely, are at risk for developing behavioral problems as a consequence of excessive parental anxiety. Although some investigators have questioned whether this syndrome actually occurs,¹⁹² others have published strong evidence of its presence in neonatal ICU (NICU) graduates.^{193,194,195,196}

Some parents react with an overprotective response after dealing with the emotional stress of multiple medical problems or even simply the admission to the intensive care nursery. Vulnerable child syndrome is occasionally observed when children have a tentative diagnosis of a minor disorder or when physicians suggest that certain neonatal findings be reevaluated in the future.

The vulnerable child response often manifests as limitations in the child's contact with the environment. Parents may limit or prevent exposure with other people or family members. In the most severe form, parents become virtual recluses with their child, refusing to leave the child to care for himself or herself. An exaggerated fear of infection, hypoxia, injury, or ridicule may be the initiating factor for some parents.

Healthcare providers must reinforce the idea of normal interaction with other children, family members, and extended communities that is limited only by the child’s tolerance. A mistake practitioners frequently make is inadvertently reinforcing the parents' overprotective behavior by accentuating the risks of infection or injury in an infant with residual problems of prematurity, congenital heart disease, or neurologic injury.

Involving children with family members and with other infants is an increasingly important part of normal development. If a child is restricted because of technologic dependence or a real infectious risk, a reasonable plan of participation should be designed so that he or she can be involved in as many age-appropriate activities as possible.

Resources for Parents and Healthcare Professionals

Extensive concern for the neonatal ICU (NICU) graduate often compels parents and other caregivers to read about conditions that require special evaluation or care after the child is discharged from the hospital. Resources available to parents and caregivers today are diverse and include medical and lay journals, books and other print materials, videotapes, and Internet sites. The information below is provided without any endorsement of the resources. Articles in medical journals are usually peer reviewed (ie, evaluated and accepted by experts in the field) before publication. The accuracy of information provided in lay journals and on Internet sites can be suspect. Consultant experts may not review information from these sources. Physicians should always investigate the particular sites that parents are using to obtain information.

Because of the emotional turmoil that having an infant in an NICU can cause, patients and caregivers often find benefit in joining a support groups. Information about such groups are available, especially on the Internet. Support by hospital personnel and other parents may be the best therapy. One must remember that specialized units or hospitals (eg, Shriners Hospitals for Children, Variety Children's Hospitals) are available to manage some conditions.

Books and Pamphlets for Parents

The following books for parents are available from online and other book sellers:

• Harrison H, Kositsky A. The Premature Baby Book: A Parent's Guide to Coping and Caring in the First Years. New York, NY: St. Martin's Griffin; 1983.
• Klein A, Ganon JA. Caring for Your Premature Baby. HarperCollins Publishers, Inc., New York; 1998
• Madden SL. The Preemie Parents' Companion: The Essential Guide to Caring for Your Premature Baby in the Hospital, at Home, and Through the First Years. Blue Ridge Summit, PA: National Book Network; 2000.
• Naseef RA. Special Children, Challenged Parents: The Struggles and Rewards of Raising a Child With a Disability. Baltimore, MD: Brookes; 2001.
• Wechsler LD, Trenti PE, Wechsler M, Doron M. Preemies: The Essential Guide for Parents of Premature Babies. New York, NY: Pocket Books; 2000.

The following books, pamphlets, and videotapes may assist parents and healthcare professionals in the care of high-risk infants during and after hospital discharge:

• Brown L, Irwin L. Parent to Parent: Encouraging Connections between Parents of Children with Disabilities. Madison, WI: Wisconsin Department of Health and Social Services Birth to Three Program; 1992.
• Brown PH, Thurman K, Pearl LF. Family Centered Early Intervention with Infants and Toddlers: Innovative Cross Disciplinary Approaches. Baltimore, MD: Brookes; 1993.
• Bryant DM, Graham MA. Implementing Early Intervention: From Research to Effective Practice. New YorkNY: Guilford; 1993.
• Catlett C, Winton PJ. Resource Guide: Selected Early Childhood/Early Intervention Training Materials. 11th ed. Chapel Hill, NC: FPG Child Development FPG Child Development Institute, University of North Carolina at Chapel Hill; 2002.
• Ensher GL, Clark DA. Newborns at Risk: Medical Care and Psycho-educational Intervention. Gaithersburg, MD: Aspen; 1986.
• Geenstein D, Miner N, Kudela E. Backyards and Butterflies: Ways to Include Children with Disabilities in Outdoor Activities. Cambridge, MA: Brookline Books; 1997.
• Geralis E, ed. Children with Cerebral Palsy: A Parents Guide. Bethesda, MD: Woodbine House; 1998.
• Green M, ed. Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents. Arlington, VA: National Maternal and Child Health Clearinghouse, 1998.
• FlehmigI. Normal Infant Development and Borderline Deviations. New York, NY: Thieme Medical; 1992.
• Hagan Arnold J, Buschman Gemma P. A Child Dies: A Portrait of Family Grief. Philadelphia, PA: Charles; 1994.
• Hanson MJ. Atypical Infant Development. Austin, TX: Pro-Ed; 1996.
• Hanson MJ, Lynch EW. Early Intervention: Implementing Child and Family Services for Infants and Toddlers Who Are at Risk or Disabled. Austin, TX: Pro-Ed; 1995.
• Hanson MJ, Vandenberg KA. Homecoming for Babies after the Intensive Care Nursery: A Guide for Parents in Supporting Their Baby's Early Development. Austin, TX: Pro-Ed; 1993.
• Johnson BH, Jeppson ES, Redburn L. Caring for Children and Families: Guidelines for Hospitals. Bethesda, MD: Association for the Care of Children's Health; 1992.
• Judge SL, Parette HP. Assistive Technology for Children with Disabilities: A Guide to Family-Centered Services. Cambridge, MA: Brookline Books; 1998.
• Kurtz L, Batshaw M, Dowrick P, Levy SE, eds. Handbook of Developmental Disabilities: Resources for Interdisciplinary Care. Austin, TX: Pro-Ed; 2004.
• Meisells SJ, Provence S. Screening and Assessment: Guidelines for Identifying Young Disabled and Developmentally Vulnerable Children and Their Families. Washington, DC: NationalCenter for Clinical Infant Programs; 1989.
• Meyer D, Vadasy P. Living with A Brother or Sister with Special Needs: A Book for Sibs. Seattle, WA: University of Washington Press; 1996.
• National Early Childhood Technical Assistance System. Part H Updates (The program for children from birth to age 2). Chapel Hill, NC: National Early Childhood Technical Assistance System; 1998.
• Pediatric Projects. Support Groups for Parents of Children in Healthcare: A Bibliography of Professional and Popular Literature. Tarzana, CA: Pediatric Projects.
• Porkorni JL. Developmental Intervention for Hospitalized Infants: The Neonatal Intensive Care Unit (NICU) Series (7 videotapes or DVDs). Van Nuys, CA: Child Development Media, Inc.
• Schleichkorn J. Coping with Cerebral Palsy: Answers to Questions Parents Often Ask. Austin, TX: Pro-Ed; 1993.
• Sell E, Hill-Mangan S, Ratzan P. Your Baby and You: Understanding Your Baby's Behavior (video and manuals). San Antonio, TX: Communication Skill Builders; 1992.
• Stengle LJ. Laying Community Foundations for Your Child with a Disability: How to Establish Relationships that Will Support Your Child after You're Gone. Bethesda, MD: Woodbine House; 1996.
• Swan WW, Morgan JL. Collaborating For Comprehensive Services for Young Children and Their Families: The Local Interagency Coordinating Council. Baltimore, MD: Brookes; 1992.
• Thom V, Krahn G, Hale BJ, et al. Supporting Families and Their Prematurely Born Babies: A Guide for Training Care Providers. Portland, OR: Child Development and Rehabilitation Center, OregonHealthSciencesUniversity; 1990.
• Well SA. A Multicultural Education and Resource Guide for Occupational Therapy Educators and Practitioners. Bethesda, MD: American Occupational Therapy Association; 1994.
• Woodrich DL. Children's Psychological Testing: A Guide for Nonpsychologists. 3rd ed. Baltimore, MD: Brookes; 1997.
• Zipper IN, Weil M, Rounds K. Service Coordination for Early Intervention: Professionals and Parents. Cambridge, MA: Brookline; 1993.

• American Academy of Pediatrics (AAP) Web site: The AAP is a national organization of pediatricians that is devoted to the health and well-being of infants and children. The site has many policy statements regarding the proper care of infants and children and offers information about the care of premature infants and childhood immunizations. The AAP bookstore sells an extensive collection of pamphlets and books that cover the medical and psychosocial care of infants and children. Among the pamphlets is Early Arrival: Information for Parents of Premature Infants.
• Preemie Health Web site of Meriter Healthy Living: This site gives information about survival of prematurely born infants and the adverse effects of preterm birth. The Introduction to the NICU section includes a glossary that helps parents become oriented to the environment. It introduces the people, equipment, and language of the NICU. Common problems, diseases, and drugs are discussed. Topics also include issues related to discharge and the emotional support of parents, including questions parents may ask after their children are discharged from the hospital. Neurodevelopmental outcomes of preemies are also covered. The site has wide-ranging information useful to both parents and professionals.
• The Premature Birth Web site of the March of Dimes Foundation: This outstanding site for parents and professionals discusses preventing prematurity and diseases of pregnancy that cause preterm birth. The site offers information about the diseases infants might have, and it provides information about neonatal nutrition, including the importance of breastfeeding. The site addresses disabilities in prematurely born infants. Resources are available in Spanish.
• Shriners Hospitals for Children: The Shriners offer care to infants and children who have qualifying medical conditions, such as spina bifida, cleft lip and/or palate, and orthopedic anomalies. Clinicians or parents may call a toll-free patient-referral line to determine if a particular child qualifies; the referral numbers are 1-800-237-5055 in the UnitedStates and 1-800-361-7256 in Canada.
• A Primer on Preemies from the KidsHealth for Parents Web site by the Nemours Foundation: This site is sponsored by medical experts at the Nemours Foundation. It summarizes the NICU and conditions common to premature infants. Resources are available in Spanish.
• Parents of Premature Babies Inc (Preemie-L): This organization offers a good compendium of on-line and off-line resources.
• NatalDoc.com: This is a Spanish Web site for high-risk pregnancy and for neonatal and pediatric information.
• Child Care Resources: This is a Web site with a list of daycare requirements needed to establish programs for special needs children.

To obtain additional information or to finding support groups, parents can also ask the neonatologist, the nursing supervisor, and/or the social worker for resources in or near the hospital. Some facilities often give parents a pamphlet with this information when their child is admitted. Community agencies, such as the March of Dimes, and religious organizations may offer support services. Local and national support groups have been organized for infants and children with certain conditions. Examples include the Down Syndrome Foundation, the Cystic Fibrosis Foundation, the Little People of America (addressing dwarfism).

Keywords

follow-up of the NICU patient, follow-up of the neonatal intensive care unit patient, posthospital care of the NICU graduate, assessment and management of the NICU graduate, neonatal ICU, preterm infant, extreme prematurity, extremely low birth weight infant, ELBW infant, very low birth weight infants, late preterm infants, discharge planning for high-risk infants, discharge follow-up, special needs infants, hospice, neurodevelopment, psychomotor testing, neurodevelopmental testing, vulnerable child syndrome, primary care physician, bronchopulmonary dysplasia, posthemorrhagic hydrocephalus, intracranial hemorrhage, hypoxic-ischemic encephalopathy, autism, anemia, special needs infant, hepatocellular liver disease, myelodysplasia, growth failure

chronic pulmonary hypertension, trisomy 13, trisomy 18, cardiopulmonary resuscitation, gastrostomy feedings, total parenteral administration, monitor use, respiratory syncytial virus, RSV, retinopathy of prematurity, ROP, small for gestational age, SGA, osteopenia of prematurity, congenital heart disease, short-bowel syndrome, chronic renal disease, gastroesophageal reflux, necrotizing enterocolitis, protein intolerance, rickets, rib fractures, megaloblastic anemia, dermatitis, diarrhea, zinc deficiency, slow wound healing, acrodermatitis enteropathica, carnitine deficiency, failure to thrive, cardiomyopathy, recurrent infection, protein-related malnutrition, sudden infant death syndrome, SIDS, treatment, diagnosis

This article does not review follow-up procedures for newborns who have malformations, chromosomal disorders, or metabolic disorders. For information about these and other subjects, please see the appropriate eMedicine articles, including the following:

• Birth Trauma
• Kernicterus
• Neonatal Abstinence Syndrome
• Neural Tube Defects in the Neonatal Period
• Perinatal Asphyxia
• Perinatal Drug Abuse and Neonatal Drug Withdrawal
• Periventricular Hemorrhage-Intraventricular Hemorrhage
• Periventricular Leukomalacia

Follow-up of neonatal ICU (NICU) graduates occurs in diverse settings, such as private offices, university centers, community health clinics, governmental facilities, and/or charitable institutions (eg, Variety Children's Hospitals, ShinersHospitals for Children). Resources for these infants may vary from state to state, and systems for the follow-up of NICU patients may differ among international healthcare providers. Therefore, this article provides general information because of the diversity of resources available to NICU graduates.

Interventions that may facilitate an optimal psychomotor outcome are discussed in the sections Developmental Follow-Up and Counseling Caregivers During and After the NICU Stay.

In 2001, Gross demonstrated the major role that a family structure has on the academic achievement of NICU graduates during formal schooling. ¹⁰⁰ Subtle academic disabilities have also been identified in long-term follow-up of extremely low birth weight (ELBW) infants and are related to so-called executive functions, such as sequencing, planning, and scheduling. ¹⁶⁴

Stress on family members who are caring for the NICU graduate can be overwhelming, both immediately after discharge and for years to come (see The Vulnerable Child). Parents have an enormously important role in the neurodevelopmental outcome of their infant, and Resources for Parents and Caregivers lists some resources to assist them in the care of their child.

Sell and Ballard edited early textbooks on the topic of outcome or care of the NICU patient and graduate. ^197, 198 In 2000, Vohr edited a monograph on the outcome of infants born very prematurely. ¹⁹⁹ In 2000, Cowett edited a monograph on nutrition and metabolism in these infants. ²⁰⁰ The early textbooks Sell and Ballard wrote are valuable educational materials that offer a historical perspective. The article authored by Vohr in 2004 ¹³⁶ and the monograph written by Cowett in 2000 ²⁰⁰ provide the best perspective on NICU-related follow-up and post-discharge nutrition of the preterm infant, respectively.

Articles written by Vohr, ¹ O'Shea, ³ and Wright ⁴ and published in the 2001 NeoReviews, a Web-based collection from the AmericanAcademy of Pediatrics (AAP), emphasize the changing characteristics of neonatal follow-up programs. A review by Perlman provides an excellent summary of the pathophysiologic mechanisms responsible for neurologic deficits that are observed in preterm infants. ²⁰¹ Finally, a review by Aylward (2005) comprehensively covers the assessment and outcomes of NICU graduates in general terms. ¹⁹⁸

For excellent patient education resources, visit eMedicine's Children's Health Center. Also, see eMedicine's patient education article Sudden Infant Death Syndrome (SIDS) because neonates who were once treated in NICUs are at increased risk of SIDS, also known as cot death.

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• Sudden Infant Death Syndrome Overview

• Sudden Infant Death Syndrome Prevention -- A Model for NICUs