Technical advances and improvements in perinatal care have been mainly responsible for the improved survival of high-risk neonates ( Fig. 19-1 , Table 19-1 , and Appendix C). A major concern persists, however, that neonatal intensive care results in an increase in the number of permanently handicapped children.
| Gestational Age (wk) | Survival (%) | NDI (%) | Survival Without NDI (%) |
|---|---|---|---|
| 22 | 5 | 80 | 1 |
| 23 | 26 | 65 | 9 |
| 24 | 56 | 50 | 28 |
| 25 | 76 | 39 | 46 |
The initial follow-up studies of preterm infants in the early 1970s described a decrease in unfavorable neurodevelopmental sequelae compared with the era before neonatal intensive care. Despite the continued decrease in mortality rates, the incidence of neurosensory and developmental handicaps initially remained constant in the 1980s; however, morbidity increased in the 1990s following a further decrease in mortality, which was associated with antenatal steroid and surfactant therapies introduced in the early 1990s. These treatments resulted in the survival of high-risk infants who previously would have died. Furthermore postnatal steroid therapy, which was widely used to prevent or treat bronchopulmonary dysplasia, resulted in higher rates of cerebral palsy. The absolute number of both healthy and neurologically impaired children in the population thus increased in the 1990s. Additional morbidity resulted from increased infection, necrotizing enterocolitis, and poor physical growth in infants of extremely low birth weight (<1 kg) and short gestation (<26 weeks).
Since 2000, the outcomes of children with a birth weight of less than 1 kg have improved; this improvement has resulted from a significant decrease in nosocomial infections and intraventricular hemorrhage, together with a decrease in the use of postnatal steroid therapy.
When outcome results are evaluated, considerable variation is noted in the results cited in different reports. One reason is that selection of patients by birth weight does not guarantee a homogeneous group, and populations studied in one center may differ considerably from those studied in another center. There are several causes for these differences. One of the most important factors is the pattern of referral to the neonatal intensive care unit (NICU). Units that receive admissions from numerous outlying hospitals have a selected population that may contain a disproportionate number of the sickest babies or may include only those infants deemed well enough to transport. In addition, patients treated in an “inborn” unit have the advantage of consistent and, presumably, good obstetric care coupled with the opportunity for immediate postnatal resuscitation and management. Inadequate resuscitation at birth and prolonged hypoxia and acidemia, together with the cold stress associated with transport that may be seen in referred patients, influence not only the outcome in the period immediately after birth but also the type and frequency of developmental sequelae. Other factors that may influence outcome include (1) the socioeconomic profile of the parents, (2) the proportion of infants with intrauterine growth restriction, (3) the incidence of extreme prematurity, (4) a selective admission policy, (5) a selective treatment policy, and (6) changes in therapy during the study period.
The major clinical outcomes that are important to preterm infants and their families are not only survival, but survival accompanied by normal long-term neurodevelopment. These goals are not easily attainable; however, the landscape has improved over the past two decades, and there are now more intact survivors who attend mainstream schools and ultimately live independently. How to preserve brain function and permit normal brain development ex utero remain enormous challenges. The period between 20 and 32 weeks after conception is one of rapid brain growth and development. Illness, hemorrhage, ischemia, metabolic disturbances such as hypoglycemia, hyperbilirubinemia, undernutrition, and infection during this time may compromise neurodevelopment. Indeed, events leading to the premature birth such as chorioamnionitis may have stimulated the release of cytokines that in turn injure the developing brain. Scores of publications continue to demonstrate inferior intellect and function in the most immature babies compared with their term peers.
Follow-up of graduates from the intensive care unit has shed the orphan role it had for so long and is now a genuine and legitimate component of neonatology. Indeed, neurodevelopmental status on follow-up has become an integral part of the primary outcome measure in most prospective randomized interventional trials involving both term and preterm infants. Absence of harm and normal long-term neurodevelopment are the desired outcome.
Measures of outcomes of neonatal care include the rate of mortality before and after discharge from the neonatal intensive care nursery, rate of rehospitalizations, and incidence of chronic medical conditions such as asthma and growth failure. Neurodevelopmental sequelae include subnormal and borderline cognitive (mental) function and neurosensory deficits such as cerebral palsy, deafness, and blindness. These sequelae have traditionally been used as outcome measures. Other outcomes include functional abilities and the ability to perform the activities of daily living. Additional measures involve special health care requirements such as the need for technologic aids, frequent physician visits and medications for chronic conditions, occupational and physical therapy, and special education and counseling. Other measures may include impact on the family, quality of life, and cost of care.
Regional outcome studies provide the most accurate data because they include all infants born in a region rather than hospital-based results. Such studies have rarely been undertaken in the United States, although they have been performed in Canada, the United Kingdom, and Australia. Results may also be reported from multigroup studies or randomized controlled trials of various therapies ( Box 19-1 ).
| Survival |
|
| Medical morbidity |
|
| Neurodevelopmental outcome |
|
| Functional outcomes |
|
| Quality of life |
| Impact on family |
| Cost of care |
The risk of neurodevelopmental problems increases as birth weight and gestational age decrease. Additional risk factors include the occurrence of neonatal seizures; severe periventricular hemorrhage ; periventricular leukomalacia ; bronchopulmonary dysplasia, defined as an oxygen requirement at 36 weeks’ postconceptional age; and severe intrauterine or neonatal growth failure, specifically a subnormal head circumference (≤2 standard deviations [SDs] from the mean) at discharge. Children born to mothers who have a low educational level or live in poverty demonstrate the additional detrimental effects of the environment. Among term-born children, risk factors for later neurologic and developmental sequelae also include perinatal asphyxia, neonatal seizures, an abnormal neurologic finding at discharge, and persistent pulmonary hypertension requiring prolonged ventilator therapy, nitric oxide therapy, or extracorporeal membrane oxygenation. Children born with multiple major malformations also constitute a group that generally has a poor developmental outcome ( Box 19-2 ).
| Birth weight <750 g or <26 weeks’ gestation |
| Periventricular hemorrhage (grade III or IV) |
| Periventricular leukomalacia or other echodense lesions |
| Persistent ventricular dilatation |
| Neonatal seizures |
| Chronic lung disease |
| Neonatal meningitis |
| Subnormal head circumference |
| Poverty or parental deprivation Congenital malformations |
Importance of Follow-Up for High-Risk Infants
Follow-up clinics should be an integral part of every NICU. Specialized care for problems of growth, sequelae of bronchopulmonary dysplasia, and adaptation is best provided within the setting of a neonatal follow-up program. This care should initially be provided by the neonatal department and then gradually transferred to developmental and educational specialists. The initial continuity of care is important to the family, who will find reassurance in the fact that the same people who were responsible for the life-saving decisions early in the infant’s life are continuing to assume responsibility for the child’s adaptation into home life. There is also a moral obligation to maintain this contact. Furthermore, even if the neonatologist does not continue the follow-up for an extended period, he or she will benefit greatly by maintaining contact with the nursery graduates and recognizing the sequelae of the early neonatal interventions.
When growth and neurodevelopmental outcomes are assessed, it is important to correct the child’s age to account for the preterm birth. This should be done at least until the child is 3 years of age. For extremely immature infants (i.e., those born at 23 to 25 weeks’ gestation), such age correction may be necessary until at least 5 years of age.
Minor Transient Problems
The first few months after the neonate’s discharge can be considered a period of convalescence for the infant and parents as well. Many infants have minor problems specifically related to being born preterm, but these may seem major problems to their parents. These problems include anemia of prematurity, umbilical and inguinal hernias, relatively large, dolichocephalic, “preemie-shaped” heads, and subtle behavioral differences. Most healthy preterm infants are discharged home at 36 to 37 weeks’ gestational age (or when they weigh about 1.9 kg). At this age they still tend to sleep most of the day, waking only for feedings; to feed slowly and not always to demonstrate hunger; to sometimes be jittery; and to have “preemie” vocalizations, which include grunts and a relatively high-pitched cry.
Transient Neurologic Abnormality
There is a very high incidence of transient neurologic abnormality during the first year of life, ranging from 40% to 80% among preterm infants. These include abnormalities of muscle tone such as hypotonia or hypertonia. Such abnormalities present as poor head control at 40 weeks’ corrected age (the expected term date), poor back support at 4 to 8 months, and sometimes a slight increase in the tone of the upper extremities. Because there is normally some degree of hypertonia during the first 3 months after term, it is difficult to diagnose the early developing spasticity related to cerebral palsy. Children in whom cerebral palsy later develops show hypotonia (poor head control and back support) initially and only later manifest spasticity of the extremities combined with truncal hypotonia. Spasticity during the first 3 to 4 months of life is an indicator of poor prognosis. Mild hypertonia or hypotonia persisting at 8 months usually resolves by the second year of life. Persistence of primitive reflexes beyond 4 months’ corrected age might be a sign of early cerebral palsy. Major neurologic handicap presents during the first 6 to 8 months after term in about 10% of newborns in the most high-risk categories; however, 90% of high-risk newborns will be or become neurologically normal after the first year of life.
Persistent Neurologic Sequelae
Major neurologic handicap can usually be defined during the latter part of the first year of life or even earlier if severe. It is usually classified as cerebral palsy (spastic diplegia, spastic quadriplegia, or spastic hemiplegia or paresis); hydrocephalus (with or without accompanying cerebral palsy or sensory deficits); blindness (usually caused by retinopathy of prematurity); or deafness. Blindness currently occurs very rarely because laser treatment or cryotherapy for severe retinopathy of prematurity may prevent the progression of this disease. The developmental and intellectual outcomes differ according to the severity of cerebral palsy. For example, children with spastic quadriplegia usually have severe mental retardation, whereas children with spastic diplegia or hemiplegia may have relatively intact mental functioning. Mental functioning is not always measurable in these children until after 2 to 3 years of age.
Cerebral palsy is an umbrella term encompassing a group of nonprogressive, noncontagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement. Most health care providers are familiar with the high rates and risk of cerebral palsy in preterm infants. Nonetheless, numerically it is term and near-term infants who account for the majority of cases of cerebral palsy despite their significantly lower risk.
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