Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention

INTRODUCTION — Neurodevelopmental impairment (NDI) is a significant long-term complication associated with preterm birth; the risk of major disability increases with decreasing gestational age.

This topic will review the approach to risk assessment and follow-up care for preterm infants, including neurodevelopmental surveillance and early intervention. The epidemiology and risk factors for long-term NDI among survivors of preterm birth are discussed separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors".)

Other complications of preterm birth and other aspects of follow-up care are discussed separately:

●(See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality".)

●(See "Overview of short-term complications in preterm infants".)

●(See "Overview of the long-term complications of preterm birth".)

●(See "Care of the neonatal intensive care unit graduate".)

DEFINITIONS

Prematurity — Degrees of preterm birth are typically defined by gestational age (GA) or birth weight; the definitions are provided in the table (table 1).

Neurodevelopmental impairment (NDI) — The term NDI is a composite and typically includes cognitive, motor, sensory, behavioral, and/or psychologic impairments.

Moderate to severe NDI is commonly defined in research studies as the presence of any of the following:

●Cognitive delay, defined by scores on standardized cognitive tests. Severe cognitive delay is defined as scores that are >2 standard deviations (SD) below the mean. Moderate cognitive delay is defined as scores that are 1 to <2 SD below the mean. This would correspond to scores of ≤70 (for severe) and ≤85 (for moderate) on the cognitive scale of the Bayley Scales of Infant Development.

●Moderate to severe cerebral palsy (CP), defined as a score of ≥2 on the Gross Motor Function Classification System (GMFCS).

●Bilateral hearing deficit/loss requiring amplification.

●Severe visual impairment with visual acuity of 20/200 or less in the better-seeing eye with best conventional correction (definition of legal blindness).

PREDICTING OUTCOME

Challenges — Not all preterm survivors will have neurodevelopmental impairment (NDI) (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Risk of NDI by gestational age'). As a result, it would be optimal to identify those survivors at the greatest risk for significant neurodevelopmental disability who would most benefit from ongoing costly comprehensive neurodevelopmental assessment and early intervention services. However, early prediction of complex academic, behavioral, and functional outcomes for preterm infants is imprecise because of the limitations of available clinical tools to accurately prognosticate long-term neurodevelopmental outcome for individuals at school age, at adolescence, and as adults. The available clinical tools to predict outcome include:

●Neuroimaging (cranial ultrasonography and magnetic resonance imaging).

●Early childhood clinical assessment during the first two years of life consisting of neurologic examination and formal evaluation of cognitive and motor function, language, and social development and behavior.

Although these tools are useful in assessing population-based or large birth cohorts, they are not specific enough to be helpful in accurately predicting outcome for each individual survivor. Nevertheless, despite their limitations, these tools are the best ones available and are used to monitor the neurodevelopmental status of the individual survivor, who is at significant risk for NDI. Early identification of survivors who are likely to have moderate to severe neurodevelopmental deficits allows for early intervention. Further assessment through school age of survivors with or at-risk for significant impairment may detect other neurodevelopmental deficits, particularly more subtle behavioral and functional impairment. This allows for additional educational support as needed. (See 'Approach for follow-up care' below.)

Tools

Neuroimaging — Advances in the development and utilization of cranial ultrasound and magnetic resonance imaging (MRI) have enhanced detection of brain injury in preterm infants and improved the understanding of the links between brain injury and neurodevelopmental outcomes [1]. In particular, neuroimaging is able to identify preterm infants with significant brain injury, who are at-risk for NDI [1,2]. However, neuroimaging poorly predicts cognitive function for the individual patients later in life. As a result, neuroimaging should not be used as the sole accurate predictor of long-term neurodevelopmental outcome for individuals.

●Ultrasonography – Cranial ultrasonography is the primary neuroimaging modality used to evaluate intracranial pathology in preterm infants and predict long-term outcome [1]. It is considerably less expensive and more readily available than MRI, although it is less sensitive. In most neonatal intensive care units (NICUs), ultrasound is routinely performed for preterm infants with a gestational age (GA) <32 weeks typically within the first few days or week of life. Subsequent serial exams are used for ongoing surveillance.

Cranial ultrasonography using both anterior fontanelle and mastoid views can reliably detect germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) and periventricular leukomalacia [1]. Ultrasonography is not as sensitive as MRI in detecting diffuse white matter abnormalities or cerebellar abnormalities in the posterior fossa, particularly during the first month of life [3]. However, extremely preterm (EPT) infants (GA <28 weeks) with normal ultrasounds at term equivalent are unlikely to have moderate or severe white matter or gray matter abnormalities on MRI performed at term-age equivalent [4]. Abnormal late ultrasound findings (35 to 42 weeks postmenstrual age) associated with an increased risk of cognitive delay and/or psychomotor delay include moderate or severe ventriculomegaly, echolucency and echodensity, severe IVH (grade III or higher), and periventricular hemorrhage [2,5,6]. As a result, it is the most commonly used neuroimaging modality for the detection of brain injury. (See "Overview of cerebellar injury and malformations in neonates", section on 'Neuroimaging' and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis", section on 'Screening'.)

Although patients with neonatal cranial ultrasound abnormalities compared with those with normal studies are more likely to have long-term NDI, approximately one-fourth of EPT infants with a normal ultrasound may still have cognitive and psychomotor delay [5]. As a result, the lack of sensitivity in detecting all patients with long-term impairment by ultrasound must be taken into account.

It also uncertain whether low-grade (grade I or II) GMH-IVH detected by cranial ultrasonography is associated with poorer neurodevelopmental outcomes, especially in EPT infants. The controversy on the effect of grade I and II GMH-IVH based on different outcomes from observational studies is discussed separately. (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome", section on 'Low-grade GMH-IVH'.)

●MRI at term gestation – MRI at term gestation may be useful in predicting long-term neurodevelopmental outcome for preterm infants at risk for NDI. In our practice, we perform MRI selectively based upon clinical risk factors in the individual patient [7,8]. We do not perform routine MRI due to its increased costs, logistics, and potential for parental anxiety without accessible evidence-based interventions. (See 'Selective MRI imaging' below.)

Neonatal MRI studies have shown that most very preterm infants (GA ≤30 weeks) have white matter abnormalities, which include increasing ventricular size, decreasing white matter volume, increasing intensity of white matter signal, and evidence of decreasing myelination [9-12]. Studies have shown correlation between MRI findings at term equivalent and long-term neurodevelopmental outcomes, particularly if the MRI is grossly abnormal (predictive of poor neurodevelopmental outcome) or normal (predictive of favorable neurodevelopmental outcome) [2,9-11,13-19]. However, a prospective cohort study from a single center reported that while MRI findings at term were associated with neurodevelopmental outcomes in the short term (ie, at two years of age), many of the correlations did not persist to age 10 years [20]. The only domains for which early MRI findings continued to correlate with at age 10 years were motor skills and behavior, whereas the correlation with cognitive function was no longer significant. In this study, environmental factors (such as maternal level of education) were more predictive of cognitive function as children grew older.

In addition, not all children with white matter abnormalities on term MRI had severe impairment, and severe neurologic impairment can occur in children without white matter abnormalities. As a result, the use of neuroimaging alone is insufficient to determine long-term outcome and follow-up intervention for individual patients [8].

The cost and challenge of performing MRI in infants also limit the routine use of MRI. Infants need to be transported to the MRI suite and sedation may be required to minimize motion artifact, requiring personnel with expertise in neonatal transport and sedation. Accurate neonatal MRI readings require expertise by knowledgeable pediatric neuroradiologists. In particular, the ability to detect mild and moderate degrees of injury on MRI may need sophisticated scanning sequences as well as proficiency in the analysis of results.

Formal clinical assessment — For preterm survivors who are at-risk for NDI, early clinical assessment can identify moderate to severe impairments. Children with significant NDI in early childhood often have persistent disability at school age and may benefit from early intervention [21-24]. (See 'Early intervention programs' below.)

Comprehensive neurodevelopmental assessment is generally reserved for at-risk survivors because it is costly and time-consuming. (See 'Identifying at-risk infants' below.)

During the first two years of life, the formal clinical assessment for NDI includes all of the following. The approach is discussed in greater detail below. (See 'At-risk infants (including <30 weeks gestation)' below.)

●Detailed neurologic examination, focusing on identifying motor deficits (see "Neurologic examination of the newborn" and "Detailed neurologic assessment of infants and children", section on 'Neurologic examination').

●Visual assessment (see "Vision screening and assessment in infants and children").

●Hearing assessment (see "Hearing loss in children: Screening and evaluation").

●Standardized tests for cognitive and motor function, language, social development, and behavior (see "Intellectual disability (ID) in children: Clinical features, evaluation, and diagnosis", section on 'Assessment of infants and young children' and "Cerebral palsy: Evaluation and diagnosis", section on 'Examination and developmental assessment').

Electroencephalography: Unproven tool — There is limited poor-quality evidence based on observational data that amplitude-integrated electroencephalography (aEEG) or conventional electroencephalography (EEG) recorded within the first seven days of life may have potential as a predictor for subsequent neurodevelopmental outcome. However, a systematic review of the literature reported that the evidence, which is based on a small number of studies, is limited due to the high risk of bias and the wide variability in study design, including EEG criteria and outcome measures [25]. As a result, aEEG and EEG should not be used clinically and should be restricted as a research tool until there are high-quality studies that show that they are accurate predictors of neurodevelopmental outcome.

APPROACH FOR FOLLOW-UP CARE

Goals — At discharge, our overall goals of follow-up care for the neonatal intensive care unit (NICU) survivor and his/her family are to:

●Effectively manage long-term sequelae of preterm birth

●Facilitate optimal growth and development of the child

●Integrate the child into the family, school system, and targeted community services

Because of the need to provide optimal care to the infants discharged from the NICU, who are primarily preterm infants, guidelines for the primary care provider in the management of these patients from the American Academy of Pediatrics (AAP) and United Kingdom National Institute for Health and Care Excellence (NICE) have been developed [26,27]. Our approach is consistent with these guidelines, which include recommendations for screening, evaluation, and referral for hearing and vision loss and neurodevelopmental disorders. (See "Discharge planning for high-risk newborns" and "Care of the neonatal intensive care unit graduate".)

Identifying at-risk infants — Our approach to providing follow-up care is focused on identifying at-risk infants at discharge as they transition to the home environment. Risk factors at discharge for NDI include (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Risk factors for NDI'):

●Gestational age [GA] <30 weeks.

●Multisystem congenital malformations.

●Neonatal course that includes any of the following conditions:

•Severe asphyxia

•Intrauterine growth retardation

•Severe intraventricular hemorrhage (IVH)

•Periventricular leukomalacia or infarction

•Meningitis

•Seizures

•Respiratory failure requiring mechanical ventilation

•Poor growth (including head growth)

●Clinically significant neuroimaging abnormalities of (eg, severe intracranial hemorrhage, periventricular leukomalacia/infarction, other evidence of white matter abnormality) (see 'Neuroimaging' above).

●Postnatal environmental factors, including socioeconomic status and maternal level of education (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Environmental factors').

Selective MRI imaging — In our practice, we perform MRI at term gestation equivalent only for infants in the following clinical settings:

●To follow-up abnormal cranial ultrasound results (eg, severe intraventricular hemorrhage, periventricular leukomalacia, and hydrocephalus) [28].

●If the infant has concerning findings on neurologic examination.

●If a congenital or metabolic defect is suspected.

●If the infant loses previously achieved neurodevelopmental milestones.

We perform MRI selectively only in these circumstances because MRI is costly, often requires general anesthesia, and it offers limited predictive information for most individual infants. However, other centers routinely perform MRI at term in all infants with a GA <28 weeks in addition to the clinical scenarios listed above [1].

If MRI is obtained, it should be performed and reviewed by an experienced and knowledgeable pediatric neuroradiology team [7]. The results should be integrated with clinical information (physical examination findings, presence of other risk factors [eg, associated conditions such as bronchopulmonary dysplasia], and neurocognitive testing) to assess the risk for developmental delay for each individual patient. In our practice, these data are used to make decisions about the frequency and duration of follow-up and the need for early intervention. Results from one case series suggest that this multilevel approach (risk factor assessment and magnetic resonance imaging [MRI] evidence of white matter injury) may help identify specific cognitive and behavioral problems in children born very preterm [29].

Initial outpatient visit — Families need to be introduced to the concept of neonatal follow-up and partnership with their primary care provider prior to discharge. In some units, the follow-up medical team meets with the family once the infant is stable and provides information, including educational material (eg, brochures) to the family and stresses both the importance of follow-up and partnership with their primary care provider. The initial follow-up visit with the primary care provider should occur within a few days to a week after neonatal discharge depending on the infant's GA and clinical status. (See "Care of the neonatal intensive care unit graduate", section on 'Initial visit'.)

This visit should evaluate the adaptation to the home environment and troubleshoot any medical concerns. There should be specific assessment of the infant's feeding behavior, frequency, and volume; safe sleep positioning; and medication dosing and administration practices; and the parents' understanding of the home feeding plan, including the way to increase the calories of the breast milk (if needed) and/or mix the formula. In addition, the physical examination should include assessment of the infant's head control, muscle tone, level of alertness and activity, and presence of asymmetric neurologic findings. The general pediatrician may use screening tools such as the Ages and Stages Questionnaire [30] and Child Behavior Checklist to screen development (table 2) and behavior prior to referral for a neurodevelopmental assessment. (See "Care of the neonatal intensive care unit graduate", section on 'Initial visit' and "Neurologic examination of the newborn" and "Developmental-behavioral surveillance and screening in primary care".)

For any patient with any suspected developmental delay, a prompt referral for comprehensive evaluation to a pediatric neurologist and/or developmentalist and early intervention is warranted. In the United States, there is significant variability between states on eligibility and referral practices for early intervention. Pediatricians should familiarize themselves with local practices. (See 'Early intervention programs' below and "Developmental-behavioral surveillance and screening in primary care", section on 'Positive screen'.)

Follow-up based upon risk stratification

Infants ≥30 weeks gestation without additional risk factors — For infants with a GA ≥30 weeks and who have no other risk factors for NDI, we suggest routine follow-up with the primary care provider. Infants in this category are at low risk for developing significant NDI and they usually do not require early intervention. For these patients, the Ages and Stages Screening Tool is an appropriate tool to screen for developmental delay. However, primary care providers should be aware these former preterm infants, including late preterm infants, are still at greater risk for long-term neurodevelopment impairment than those born at term and should be alert to any sign or symptom of delay or neurologic abnormality. (See "Developmental-behavioral surveillance and screening in primary care".)

Children who fail a screening test or in whom there is a concern of delay or neurologic abnormality should be promptly referred for additional developmental assessment and evaluation. (See "Developmental-behavioral surveillance and screening in primary care", section on 'Positive screen'.)

At-risk infants (including <30 weeks gestation) — Care for at-risk infants (ie, GA <30 weeks, prolonged complicated NICU course, and/or other risk factors) should be provided collaboratively between the primary care provider and a high-risk neonatal follow-up program consisting of a multidisciplinary team with expertise in the care of ongoing medical problems (administration of multiple medications, severe chronic lung disease, and poor growth) and neurodevelopmental and nutritional/feeding follow-up assessment [27]. Newborn follow-up programs are also a readily available resource when concerns are identified during primary care visits. (See 'Identifying at-risk infants' above and "Care of the neonatal intensive care unit graduate".)

Follow-up schedule — In our center, the initial visits to the neonatal follow-up clinic consist of the following:

●Corrected age four months:

•Assess growth and nutritional needs

•Detect severe neurologic abnormalities that may require intervention (occupational or physical therapy)

●Corrected age 8 to 12 months:

•Evaluate for early signs suggestive of cerebral palsy (CP) or other neurologic abnormalities

•Hearing and vision assessments

•Perform initial formal neurodevelopmental assessment with a standardized tool

●Corrected age 18 to 24 months:

•Ongoing formal assessment of cognitive and language development

•Complete neurologic examination to confirm any persistent neurologic deficits, including CP

●After age two years – Additional follow-up is dependent on the needs of the child based on previous assessment and includes further cognitive testing; academic achievement standardized testing in mathematics, reading, and spelling starting at school age; and neurophysiologic evaluation (attention, executive function, memory, and fine and gross motor function).

Follow-up assessments

●Neurologic examination – Neurologic assessment during the first years of life focuses on identifying infants with the following:

•Muscle tone abnormalities – Early muscle tone abnormalities are common, ranging from 40 to 80 percent of preterm infants, and may become more apparent over time [31,32]. These include hypotonia with poor back support or hypertonia with slightly increased tone in the upper extremities. Abnormal tone at four months corrected age, especially hypertonia, is an indicator of poor prognosis. In addition, evaluation of infants in the sitting position at eight months corrected age may identify children with lower extremity hypertonia at risk for later CP, as they often will fall backward when placed to sitting. (See "Cerebral palsy: Classification and clinical features", section on 'Early signs of cerebral palsy' and "Detailed neurologic assessment of infants and children", section on 'Tone and strength'.)

•Abnormal head growth – By eight months corrected age, abnormal head growth (defined as falling off percentile curves or rapid acceleration with large fontanels) is strongly related to poor neurodevelopmental outcome. (See "Macrocephaly in infants and children: Etiology and evaluation" and "Microcephaly in infants and children: Etiology and evaluation".)

●Cerebral palsy – Clinicians should monitor very preterm infants during office visits for early neurologic signs of CP such as initial hypotonia, spasticity, abnormal postural reflexes, increased tone, abnormal body movements, and deep tendon reflexes.

Standardized motor assessments (eg, Prechtl's General Movements Assessment [GMA], Hammersmith Infant Neurological Examination [HINE]) can facilitate earlier detection and intervention for CP. These assessments may also correlate with cognitive outcomes in preterm infants, though with lower predictive validity than for neuromotor outcomes [33-37]. Early assessment and diagnosis of CP is discussed in greater detail separately. (See "Cerebral palsy: Evaluation and diagnosis", section on 'Examination and developmental assessment'.)

Patients demonstrating concerning findings should be referred for evaluation by a pediatric neurologist. Patients diagnosed with CP require further evaluation and care from a multidisciplinary team including neurologists and physical and occupational therapists. Children with the diagnosis of CP should also undergo functional assessments to determine the degree of impairment. (See "Cerebral palsy: Classification and clinical features" and "Cerebral palsy: Overview of management and prognosis".)

Data on the prevalence of CP among surviving preterm infants are presented separately. (See "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Prematurity'.)

●Hearing – NICU graduates should be screened for hearing loss using automated auditory brainstem response screening prior to discharge. Hearing screen should be repeated at five to six months corrected age or sooner if there are concerns about hearing loss. Formal audiologic assessment should be performed if the neonate does not pass the hearing screen. Patients who are found to have sensorineural hearing loss, auditory neuropathy, or permanent conductive hearing loss, should be referred to a multidisciplinary team (audiologists, otolaryngologists, and speech pathologists) for management. (See "Screening the newborn for hearing loss", section on 'Neonatal intensive care unit' and "Hearing loss in children: Screening and evaluation" and "Hearing loss in children: Treatment".)

●Vision – Very preterm infants are at increased risk for retinopathy of prematurity (ROP). At-risk infants (based upon GA, birth weight, and other risk factors) should undergo retinal screening during the NICU course. Indications for and frequency of screening for ROP are discussed separately. (See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening", section on 'Screening'.)

Former preterm infants are at risk for other ophthalmologic abnormalities including reduced visual acuity, strabismus, myopia, and astigmatism, and should be screened for these disorders by an ophthalmologist at 9 to 12 months of corrected age. A later assessment of visual acuity prior to the start of school is also indicated as the emergence of myopia may occur at this time. (See "Care of the neonatal intensive care unit graduate", section on 'Vision' and "Care of the neonatal intensive care unit graduate", section on 'Vision problems'.)

●Neurodevelopmental assessment – Screening for cognitive and motor impairment is imperative to identify infants who would benefit from early intervention and special educational accommodations. Preterm infants are also at risk for difficulties with complex language function [38]. The primary care provider may use screening tools such as the Ages and Stages Questionnaire [30] and Child Behavior Checklist to screen development (table 2) and behavior prior to referral for a neurodevelopmental assessment. (See "Developmental-behavioral surveillance and screening in primary care".)

In our neonatal follow-up clinic, the first formal developmental assessment is typically performed at eight months corrected age using the Bayley Scales of Infant Development. The Bayley Scales were developed for children 1 to 42 months of age and include evaluations of cognition, language, motor, and social-emotional and adaptive behavior. These scales yield developmental indices with a mean of 100. In the first year of life, motor skills are heavily weighted; however, by the second year, cognition, language, and behavior may be better assessed. Formal developmental assessment using the Bayley Scales is repeated at 18 to 24 months corrected age along with a neurologic examination.

Additional details regarding tests for assessing cognitive and adaptive functioning in infants and young children are provided in a separate topic review. (See "Intellectual disability (ID) in children: Clinical features, evaluation, and diagnosis", section on 'Assessment of infants and young children'.)

Early intervention programs — Early intervention (EI) programs appear to be effective at improving neurodevelopment in preterm infants through early childhood [39-42]. In a meta-analysis of 16 randomized and quasi-randomized trials, EI improved cognitive function in infancy and preschool age, but the differences were no longer statistically significant at school age [39]. A subsequent randomized trial found that a preventive EI program had minimal long-term effects of neurodevelopment (with the exception of improved achievement in mathematics); however, parents in the EI group were less likely to experience depressive symptoms [43]. There is also evidence that EI programs may improve the early childhood outcome of high-risk preterm children, especially those from marginalized socioeconomical groups [40]. EI programs vary in their timing, setting, duration, intensity, and focus, and it remains uncertain what components, if any, have significant long-term effects. (See "Developmental-behavioral surveillance and screening in primary care", section on 'Early intervention or special education services'.)

In the United States, the Individuals with Disabilities Education Act (IDEA), a federal law, mandates EI for eligible patients between birth and three years of age. Individual states are responsible for the delivery of EI. Primary care providers should be familiar with the state regulations of their community. (See "Definitions of specific learning disorder and laws pertaining to learning disorders in the United States", section on 'Individuals with Disabilities Education Act'.)

Each state is required to identify and evaluate patients at risk or who currently demonstrate developmental delays or disabilities. In most states, patients discharged from NICU meet the eligibility criteria for diagnostic evaluation, which consists of a multidisciplinary set of assessments (eg, medical, nutritional, speech/language, hearing, vision, development, and family). However, eligibility for EI differs from state to state and not all NICU graduates will qualify in some states. Unfortunately, many children undergo their initial assessment for early intervention and are found to have a normal neurologic exam and are thus discharged from EI program. It is important to evaluate children at subsequent time points for the emergence of possible developmental delay. (See "Developmental-behavioral surveillance and screening in primary care", section on 'Approach to screening'.)

SUMMARY AND RECOMMENDATIONS

●Definition – Preterm infants are at increased risk for neurodevelopmental impairment (NDI) compared with individuals born full term. NDI is a composite term that includes cognitive, motor, sensory, behavioral, and/or psychologic impairments. The risk of impairment increases with decreasing gestational age (GA). (See "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Risk of NDI by gestational age' and 'Definitions' above.)

●Identifying at-risk infants – Our approach to follow-up care is focused on identifying at-risk infants at discharge as they transition to the home environment. (See 'Identifying at-risk infants' above.)

Risk factors at discharge for NDI include (see "Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors", section on 'Risk factors for NDI'):

•GA <30 weeks

•Multisystem congenital malformations

•Abnormal findings on neuroimaging (see 'Neuroimaging' above)

•Neonatal course that includes any of the following conditions:

-Severe asphyxia

-Intrauterine growth retardation

-Severe intraventricular hemorrhage (IVH)

-Periventricular leukomalacia or infarction

-Meningitis

-Seizures

-Respiratory failure requiring mechanical ventilation

-Poor growth (including head growth)

●Follow-up for low-risk infants – For infants with a GA ≥30 weeks who have no other risk factors for NDI, we suggest routine follow-up with the primary care provider. However, preterm infants in this category are still at greater risk for NDI compared with term infants and they should undergo routine developmental surveillance. (See "Developmental-behavioral surveillance and screening in primary care".)

●Follow-up for at-risk infants – Care for at-risk infants should be provided collaboratively between the primary care provider and a high-risk neonatal follow-up program.

During the first two years of life, at-risk infants should undergo periodic clinical assessments for NDI, including all of the following (see 'At-risk infants (including <30 weeks gestation)' above):

•Detailed neurologic examination, focusing on identifying motor deficits (see "Detailed neurologic assessment of infants and children", section on 'Neurologic examination').

•Visual assessment (see "Vision screening and assessment in infants and children").

•Hearing assessment (see "Hearing loss in children: Screening and evaluation").

•Standardized tests for cognitive and motor function, language, social development, and behavior (see "Intellectual disability (ID) in children: Clinical features, evaluation, and diagnosis", section on 'Assessment of infants and young children' and "Cerebral palsy: Evaluation and diagnosis", section on 'Examination and developmental assessment').

●Selective magnetic resonance imaging (MRI) – In addition to the assessments listed above, we perform MRI at term gestation equivalent for infants in any of the following clinical settings (see 'Selective MRI imaging' above):

•Abnormal cranial ultrasound (eg, severe intraventricular hemorrhage, periventricular leukomalacia, and hydrocephalus)

•Concerning findings on neurologic examination

•Congenital or metabolic defect is suspected

•If the infant loses previously achieved neurodevelopmental milestones

●Early intervention – Early intervention (EI) programs appear to be effective at improving neurodevelopment in preterm infants through early childhood. Eligibility criteria for EI vary from region to region; however, most patients discharged from the NICU meet criteria for diagnostic evaluation. (See 'Early intervention programs' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Yvette Johnson, MD, MPH, who contributed to an earlier version of this topic review.