To support decision-making in the primary care medical home, this clinical report links preterm birth and perinatal complications to early childhood developmental disability risks. It consolidates extensive contemporary outcome research from 2005 onward into an easy-to-use framework and stratifies prematurity and NICU experiences by degree of risk for developmental impairments. This framework informs and prioritizes point-of-care screening and surveillance strategies for pediatricians caring for children born preterm, guides additional assessment and referral for appropriate therapies, and offers opportunities for reassurance (when applicable) in office settings.

One in 10 infants is born preterm at less than 37 weeks’ gestation.1  Preterm birth and its complications are the leading causes of neonatal mortality and morbidity in the United States.2  Other perinatal conditions, such as hypoxic-ischemic encephalopathy (HIE), occur more commonly in late preterm and term infants and, as in preterm infants, carry a high burden of neurodevelopmental morbidity.3  Advances in perinatal and neonatal interventions have resulted in a decrease of overall infant mortality4,5  with improved survival of extremely preterm infants6  and late preterm and term infants with HIE.7  However, early identification of neurodevelopmental morbidity in NICU graduates remains a priority.8 

In the policy statement “Hospital Discharge of the High-Risk Neonate” (reaffirmed 2018), the American Academy of Pediatrics (AAP) recommends that primary care pediatricians provide longitudinal developmental monitoring of high-risk infants and consider collaborations with multidisciplinary clinics as comprehensive follow-up options for those infants identified at hospital discharge as requiring the care of multiple disciplines.9,10  Directors of 183 academic and private multidisciplinary high-risk infant follow-up clinics in the United States reported 50% to 80% attendance of infants referred to high-risk clinics; however, no-show rates increased with subsequent follow-up appointments and clinics were mostly attended by children born very or extremely preterm (less than 30–32 weeks’ gestation). As a result, the vast majority of children born preterm received management in primary care.11  Many high-risk neonatal follow-up clinics are located in urban areas, and in 2018 more than half of the surveyed NICU programs in the United States lacked a plan for meeting the needs of families living in rural and underserved areas.12  Care for children and families living in rural and underserved areas may, however, be changing with the emergence of telehealth access to multidisciplinary pediatric medical subspecialists. Moderate and late preterm (32–36 weeks’ gestation) infants who are often not eligible for follow-up clinics constitute the majority of all infants born preterm. Thus, primary care pediatricians care for the majority of infants, children, and youth with a history of preterm birth and almost exclusively follow the 75% of preterm infants who were born between 34 and 36 weeks’ gestation and who are at increased risk for neurodevelopmental problems compared with their term counterparts.13  Of note, the term primary care pediatricians (PCPs) is used throughout this paper but it also recognizes other clinicians who may care for children born preterm, including family physicians and nurse practitioners or physician assistants.

Although a substantial amount of literature addresses severe neurodevelopmental disabilities associated with preterm birth and its complications, such as cerebral palsy, intellectual disability (ID), visual impairment, and hearing loss, extrapolating large studies about the risk and clinical decision-making for individual patients can be challenging.14  Further, it is difficult to know how to respond to infant risk factors as they relate to less severe developmental disabilities (such as specific learning disability, developmental coordination disorder, speech and language impairment, emotional problems, and neurobehavioral issues). PCPs play a critical role in the longitudinal, timely, and coordinated care needed by high-risk infants during their early childhood years—assessing growth, development, feeding, and behavior; mitigating functional limitations; and determining appropriate medical subspecialty and community level supports.10,15  Additionally, the role of PCP in assessing and mitigating effects of social determinants of health that may add to perinatal risk factors is receiving increasing recognition.16  PCPs also follow a growing percentage of high-risk infants who develop without severe disability17  and whose family and caregivers benefit from reassurance when diminishing risk is evident. This clinical report links preterm birth and its complications to early childhood developmental disability prevalence data and consolidates them into an easy-to-use, point-of-care framework that supports pediatricians with enhanced childhood surveillance and clinical decision-making for infants born preterm. The clinical report focuses on preterm birth and associated perinatal conditions that affect neurodevelopmental outcomes and does not specifically account for other risk factors (eg, prenatal alcohol exposure).

Changes in prenatal and infant care practices have substantially improved preterm infant survival since the mid-1990s, with the introduction of antenatal steroid use to induce lung maturity,18  surfactant use to improve preterm infant lung function,19  and hypothermia to address neonatal hypoxic ischemic encephalopathy.7  Contemporary studies of infants born preterm who benefited from these interventions and others are most relevant for the purposes of developmental risk stratification.20  As studies often include a wide range of gestational ages, birth weights, neonatal complications, and ages at follow-up, outcomes may include wide ranges of prevalence of developmental disabilities. More recently, use of specific gestational age groups has clarified risk estimations and informed clinician performance.21 

Low birth weight and decreased gestational age are known to be strong predictors of abnormal developmental outcomes. However, other neonatal complications, including chronic lung disease, severe intraventricular hemorrhage, HIE, and neonatal infections, further increase the risk for adverse sequelae. Neonatal conditions that carry a higher probability of early presentation of severe neurodevelopmental disabilities provide a foundation for risk stratification during infancy, childhood, and early adulthood.22,23  The developmental consequences associated with high-severity, low-frequency neonatal conditions are manifested as functional limitations (eg, delayed or atypical developmental milestones) in infants and during early childhood, highlighting the important role of the pediatrician in health supervision, developmental screening, and developmental surveillance.24  Standardized developmental screening, adjusted for a child’s corrected age (if under 24 months), is particularly crucial in infants with higher risk of developmental delays. Developmental surveillance is an important process that involves eliciting caregiver concerns, recording milestone attainment, observing behavior, examination, and applying clinical judgment during health supervision visits.25  With a history of preterm birth, clinicians seek to personalize a child’s risk for functional limitations based on the nature of child’s prematurity and presence or absence of neonatal complications.

Increased awareness of individual risk optimizes timely developmental surveillance, referral to early intervention (EI) programs and caregiver and family support services, and clinical decision-making and may decrease the likelihood of medical complications.10  Further, developmental surveillance in the context of a medical home can mitigate postnatal psychosocial complications (family and caregiver mental health conditions, lead exposure, other social determinants of health, etc) associated with developmental sequelae.26  Medical care coordination and community-based supports informed by documented perinatal course and linked to primary care developmental screening and surveillance are evidence of a coordinated continuous system of care.15,24,25  Ultimately, the PCP must weigh the risks related to the pre- and perinatal course, the family’s capacity to support the child, and service availability in the local community to optimize recommendations for individual families.

Preterm birth and its co-occurring conditions are the most common contributors to a high-risk neonatal course. Infants born preterm, by definition are born before 37 weeks’ gestation and are further categorized by gestational groups as late (34–36 weeks) and moderately preterm (32–33 weeks), very preterm (28–31 weeks), and extremely preterm (<28 weeks) infants. Less common high-risk neonatal conditions that result in developmental disabilities include term or preterm infants born with congenital infections (such as cytomegalovirus), fetal exposure to substances such as alcohol or medications, anomalies (such as congenital heart disease, diaphragmatic hernia, or structural brain disorders), or genetic conditions. Late preterm and term HIE (less than 1% of all deliveries) also carry risks for early presentation of developmental disabilities.7 

This report’s framework for assessing risk is informed by the last 2 decades of research on preterm outcomes. The Appendix compiles contemporary outcome studies summarizing the prevalence ranges for severe developmental disabilities associated with prematurity and neonatal complications in developed countries. The Appendix also lists the prevalence of developmental disabilities in the general pediatric population.

In the framework (Fig 1), risk is stratified by how much more prevalent a developmental disability is in a population of children with a history of prematurity or its neonatal complications, in comparison with the risk for the general pediatric population (GPP). Although the degree-of-risk categories defined below are somewhat arbitrary, they are clinically relevant. Conditions that have at least a 10 times greater risk of a disability than the GPP are labeled “VERY HIGH RISK.” This group includes risks for conditions that are as high as 40 times greater than the GPP risk. The next lower “HIGH RISK” category reflects risks of disability that are 5 to 9.9 times greater than the risk of the GPP. The range of “MODERATE-LOW RISK” reflects risks 1.1 to 4.9 times the GPP risk. None of the conditions had risks at or less than the GPP risk, so the isolated term of “low risk” was omitted.

  • VERY HIGH RISK: disability prevalence is 10 or more times greater than expected in the GPP.

  • HIGH RISK: disability prevalence is 5.0 to 9.9 times greater than expected in the GPP.

  • MODERATE-LOW RISK: disability prevalence is 1.1 to 4.9 times greater than expected in the GPP.

To put the risk framework into perspective for the reader, we will describe the risk for cerebral palsy (CP) in children with a history of preterm delivery without other neonatal complications. The general pediatric population born at term has a CP prevalence of approximately 0.31%. For a child born extremely preterm (<28 weeks’ gestation and a published prevalence of CP between 7.2% to 14% for this patient population), the risk of CP is categorized as VERY HIGH risk, or 23 to 45 times greater risk of CP than the GPP. A very preterm infant (born at 28–31 weeks’ gestation with a published prevalence of CP between 6.2% to 8.7% for this patient population) still is categorized as VERY HIGH risk or 20 to 28 times greater risk of CP than the GPP. An infant born at greater than 32 but less than 37 weeks’ gestation, for whom the published prevalence of CP is 0.67% to 0.8%, is categorized as MODERATE-LOW risk, or 2 times greater risk of CP than the GPP.

The prevalence of developmental disabilities in the GPP in the United States (Appendix) is described in the 2019 National Health Interview Survey (NHIS), a nationally representative survey of children27  3 through 17 years of age. Developmental disabilities for which prevalence were reported included CP (0.31%), ID (1.1% to 2.5%), deafness or severe hearing loss (0.3%), blindness or severe vision impairment (0.16%), and autism spectrum disorder (ASD [1.74%]). The NHIS prevalence for ID did not include children identified with early childhood developmental delay or global developmental delay and, thus, likely underestimates the GPP for ID. For this report, we used a more inclusive GPP prevalence for early childhood cognitive delays of 2.5%.28  For hearing loss, the NHIS included a broad range of impairments. Thus, we used more specific data for the prevalence of deafness or severe hearing loss29  for the purposes of risk stratification (Appendix). Unlike other prevalence data, ASD prevalence was not provided by the NHIS; up-to-date data can be obtained through the Centers for Disease Control and Prevention Autism Developmental Disabilities Monitoring Network. The Autism Developmental Disabilities Monitoring Network reports the prevalence of autism by 8 years of age is 23.0 per 1000 children or 1 in 44.30 

In Fig 1, PCPs using information from a child’s NICU Discharge Summary or other neonatal hospital discharge documentation may proceed down the left side of the framework until their patient’s degree of prematurity or presence of a neonatal complication is identified and follow the arrow to degrees of risk (very high, high, moderate-low) for severe developmental disabilities presenting in early childhood. PCPs can then use the color-coded risk-satisfaction information to discuss care plans with family, document clinical decision-making, and/or determine the need for additional subspecialty providers or multidisciplinary care. Figure 1 offers a practical and pragmatic algorithm to risk assessment and supports the PCP in the role of performing early childhood screening,24  close developmental surveillance at all visits, and targeted assessments for developmental concerns when indicated.31  The authors consolidated extensive literature (Appendix) into this framework (Fig 1) to facilitate pediatric assessment of developmental risk in patients born preterm. The framework is meant to link degree of risk based on published data to clinician action for individual patients and is not formally validated. Thus, if PCPs suspect developmental delay such as CP, in the absence of significant risk, they should use their judgement to address concerns and consider referral to pediatric neurology or other professionals for comprehensive assessments, as appropriate.

Neurodevelopmental disabilities presenting in early childhood are more likely to be considered severe, to occur at lower frequency, and to be diagnosed by physicians. These early presentations include vision impairment and hearing loss, CP, and significant cognitive adaptive delays (such as global developmental delay). Milder forms of cognitive disabilities may not be identified until school age in some children. Conditions that present later in childhood, often after school entry, are of lower severity and of higher frequency and are more likely to be identified by other professionals, such as teachers and therapists or families and caregivers. Examples of high-frequency, lower-severity “later” presentations include learning disabilities, language impairments, developmental coordination disorder, and concerns about behavior or mental health. The classifications of “severe versus mild,” “high- versus lower-frequency,” “major versus minor,” or “early versus later” are imperfect and occasionally misleading because some more severe presentations are identified later, and disabilities that usually present later may be problematic enough to emerge in early childhood.14  Further, children born preterm or with neonatal complications who do not present with early severe disabilities may have multiple co-occurring mild disabilities, and although individually these conditions may be less severe, the constellation of co-occurring conditions can be functionally impairing.

A brief review of the nature of prematurity and the neonatal complications associated with preterm birth and their risk relationship to developmental disabilities is presented in the following section, followed by descriptions of primary signs and symptoms in early childhood that suggest risks for severe developmental disabilities, including a guide to specific developmental surveillance considerations based on the age at the time of the office visit (Fig 2).

The degree of prematurity is a strong and consistent risk factor for all neurodevelopmental disabilities, and at lowest gestational ages, there is an inverse relationship between the risk for disability and gestational age.32  Extreme preterm birth (<28 weeks’ gestation) accounts for less than 1% of all deliveries but contributes to the greatest rates of neurodevelopmental disabilities. The risk for severe neurodevelopmental disabilities with neonatal complications such as intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and necrotizing enterocolitis (NEC) increases with decreasing gestational age. When present, these diagnoses contribute significant additive risk to gestational-age risks alone.

The framework (Fig 1) indicates very high risks in children born extremely preterm (<28 weeks’ gestation) for all developmental disabilities, and the risk remains very high for CP and ID in children born at 28 to 31 weeks’ gestation. Infants born at 28 to 31 weeks’ gestation continue to carry a very high risk for CP and a high risk for ID and hearing loss but a moderate risk for vision impairments. Moderately and late preterm infants (32–36 weeks’ gestation) have a moderate-low risk for ID, CP, hearing loss, and vision impairment compared with the GPP.

IVH and white matter injury or periventricular leukomalacia (PVL) contribute to increased risk of neurodevelopmental disabilities, with higher grades of injury conferring greater risk. IVH occurs when fragile premature vessels of the germinal matrix rupture perinatally.33  In Fig 1, grade III to IV IVH confers a very high risk of severe developmental disability, particularly when grade IV IVH, bilateral disease, or need for ventriculoperitoneal shunting is present. The prevalence of CP in infants with a history of grade III to IV IVH is significantly greater than gestational age-matched controls and confers additional risks for ID, hearing loss, and vision impairment.3235  Grade I to II IVH is associated with less risk than grade III to IV IVH but still a very high risk (greater than 10 times the GPP) for CP and hearing loss.33,36  Neuroimaging modalities such as MRI have improved the abilities to detect more subtle white matter injury, leading to a broader range of risk assessments. PVL is a result of hypoperfusion of border zone regions in the brain, resulting in periventricular focal necrosis, cystic formation, or diffuse white matter injury.3  Cystic periventricular leukomalacia has been associated with a very high risk of CP and ID.37  However, with the ability to detect more subtle white matter changes, this relationship is likely blunted with less severe white matter injury. Additional neuroimaging findings such as severity of PVL,38  white matter abnormalities,37,39  requirement for shunt,35  ventricular dilation,40,41  cerebellar injury,42  and volume loss further increase an infant’s risk for adverse neurodevelopmental outcomes. There is some evidence for an association between IVH or white matter injury and sensory impairments and/or later-onset, less severe developmental disabilities, although the attributable risk is difficult to quantify based on the current literature.

HIE can occur when there is an interruption of cerebral blood flow in the fetus, the etiology of which can be maternal, placental, or fetal in origin.43  Various perinatal signs, such as low 5-minute Apgar score, neonatal seizures, and blood acidosis, predict the severity of HIE.44  HIE of any degree (mild, moderate, or severe) occurs in 1 to 2 per 1000 births.45  The risk for disability and impaired cognitive development correlates with the severity of HIE. Despite advances in perinatal care, moderate-to-severe HIE in late preterm and term infants remains an important cause of mortality and subsequent long-term neurodevelopmental disability.46  Therapeutic hypothermia (TH) is recommended in neonates ≥35 weeks’ gestation with moderate to severe HIE.47  Despite continued very high risk for severe developmental disability overall (greater than 10 times that for GPP), TH has been shown to have increased survival with normal neurologic function at 18 months of life in infants with HIE compared with those who do not receive TH intervention.7  Infants with mild HIE, representing 50% of all HIE, are perceived as low risk for neurodevelopmental disability at this time, and TH is currently not the standard of care.48  However, up to 25% of infants with mild HIE have recently been studied and have atypical outcomes.49,50  There is a growing trend to use TH in neonates with mild HIE, although it is unclear whether risks outweigh benefits at this time.51 

In the past, BPD associated with preterm birth was attributed to unintended effects of barotrauma and oxygen toxicity.52  In current neonatology practice, BPD is attributed to atypical development of the preterm lung, seen almost exclusively in infants with extremely low birth weight.53  Continued need for oxygen supplementation by the infant at 36 weeks’ postmenstrual age (PMA) is most often identified as the marker for chronic lung disease attributable to BPD.

As with other neonatal conditions, mortality attributable to BPD has diminished in the past 2 decades, but its morbidity has increased from 32% in 1993 to 47% in 2012.32  Children with BPD frequently develop additional chronic co-occurring conditions as they age, including recurrent respiratory illnesses and hospitalizations, growth failure, and increased risk for developmental delay.54 

In a summary of numerous preschooler outcome studies, “the impact of BPD is similar in magnitude to, and independent of, the impact of significant perinatal brain injury or retinopathy of prematurity.”54  However, risk varies, even within cohorts of infants discharged with BPD; higher risk is associated with increased respiratory supports, such as need for tracheostomy55  and prolonged duration of mechanical ventilation.56,57  In outcome studies of school-aged children, BPD also predicts continued risk for other less severe neurodevelopmental disabilities such as poor motor outcomes (both gross and fine motor), postural and coordination problems, and behavioral difficulties.58  The long-term effects of poor pulmonary function impact exercise capacity, which itself is associated with poorer cognitive and behavioral outcomes.59 

ROP is a disease that affects the immature vasculature in the eye of the preterm infant (like IVH, almost exclusively in infants born before 32 weeks’ gestation in the United States).60  ROP is defined by the anatomic location of disease, referred to as zones (I, II, and III) and the vascular abnormalities identified as stages 1 (mild) to 5 (retinal detachment). When ROP is severe or referred to as type 1 (6% to 13% of total ROP cases), management often progresses to surgical intervention, such as laser therapy, or more recently, bevacizumab injections. More commonly, when ROP is determined to be mild or moderate disease, referred to as type 2 (88% to 94% of total ROP cases), infants are usually monitored until typical maturation occurs.61 

Severe ROP results in bilateral blindness with no or poor functional vision (less than 20/20 in both eyes) and occurs in 3% to 5% of infants born before 30 weeks’ gestation. Severe ROP appears to be part of a “clustering effect”62  and, when present, predicts significant risk of blindness, bilateral hearing loss, cerebral palsy, ID, and death or severe disability (neurodevelopmental impairment [NDI]) at age 11 years.63,64  In addition to ROP, infants born preterm, including moderate and late preterm infants, are more commonly at risk for less severe visual impairments, such as strabismus, amblyopia, high refractive errors, cataracts, and effects of cerebral (cortical) visual impairment.65 

NEC is a perinatal condition with a frequency inversely related to gestational age. It occurs in 3% to 9% of preterm infants and can occur rarely in term infants.66  When present, it portends at least an additive risk of mortality and neurodevelopmental morbidity in infants with other co-occurring perinatal conditions. In a large national cohort, extremely low birth weight infants with NEC had significantly higher rates of morbidity at 18 to 24 months compared with those without NEC. The need for surgical intervention for NEC identifies the most severely ill infants, with 38% of survivors demonstrating severe developmental disabilities.67  The presence of surgically treated (versus medically treated) NEC identifies infants with independent risk of mortality and long-term severe NDI, separate from other risk factors related to prematurity and perinatal course.6870 

NDI is a term for severe developmental disabilities associated with preterm birth that most often presents early in infancy or during toddler years. For research purposes, NDI is defined as children at 2 years’ corrected age with the composite outcome of a Bayley Scales of Infant Development III cognitive score <70, a Bayley Scales of Infant Development III motor score <70, a Gross Motor Function Classification Scale level ≥2 (with or without moderate or severe cerebral palsy), bilateral blindness, and/or severe hearing loss.8  NDI is most often experienced by extremely premature infants. As a general rule, the more severe the neurodevelopmental outcome, the earlier in life NDI will present with functional limitations or delayed developmental milestones. For example, children who are diagnosed later in childhood with severe ID usually present in their first year with global developmental delays, whereas features of mild ID may not be apparent until school age, with persistent delays in language, problem solving, and adaptive or daily living skills. Neurodevelopmental outcomes that present later in childhood are often of lower severity and include problems with academic underachievement, speech intelligibility, executive function (eg, attention deficit/hyperactivity disorder), emotional regulation (eg, anxiety), neuromotor skill acquisition (such as developmental coordination disorder), milder neurosensory dysfunction (eg, strabismus, hearing loss), and quality of life.14,71 

CP is caused by disturbances to the developing brain and is defined as a disorder of movement and posture that limits activity.72,73  The prevalence of CP in the United States is approximately 3.1 in 1000 children.27  The greatest preponderance of CP in infants born preterm is spastic in nature, and within the spasticity group, three-quarters have bilateral findings.74  CP has historically been identified between 12 to 24 months of age; however, newer diagnostic tools such as MRI neuroimaging, Prechtl’s general movement assessment, and the Hammersmith Infant Neurologic Examination are effective in earlier detection of CP72  and are being used before discharge from the NICU and in the newborn period to identify infants at risk for motor disabilities. CP is most often suspected by observation of delayed acquisition of gross or fine motor milestones, by asymmetry of function, or by atypical tone or posture. Screening for motor disorders is recommended at 9, 18, 30, and 48 months of age in all children.24,75  Before 9 months of age, pediatricians can use developmental surveillance to observe infant examinations for any asymmetry, persistent fisting, and/or no reaching, early atypical rolling, and inability to prop sit, which may be signs of abnormal tone. For children with very high risk of CP, at visits even before the routine 9-month motor screening visit, earlier developmental surveillance of motor disability may be present, including excessive head lag, posturing, persistent primitive reflexes, asymmetry of movement, motor delay, or gross motor milestones that appear to be acquired excessively early or in an unusual sequence, such as rolling by arching back at the age of 1 month. Early milestone acquisition may be driven by unusually strong primitive reflexes or tone abnormalities, which are associated with CP. Atypical infant motor milestones achieved out of sequence can include the ability to roll before achieving prone position on the elbows, or to crawl or stand before sitting, and may signify tone abnormalities. Similarly, atypical tone is suggested by asymmetry in sitting or crawling without reciprocal movement of all 4 limbs.75 

At the 9-month visit, recommended screening24  should ensure that children are able to roll to both sides, sit well without support, demonstrate motor symmetry, and grasp and transfer. Children who are at high-risk for CP and are seen by their pediatrician between the routine 9- and 18-month screening visits benefit from sensitive observation and developmental surveillance of gross and fine motor skills (Table 1). For example, handedness is unusual before 18 months of age and may indicate asymmetry of tone and function on the opposite side. Acquisition of grasp is refined in the final months of the first year such that a neat pincer and finger manipulation should be present by 12 months. Similarly, delayed walking or asymmetry in heel strike or persistent toe walking may be indicators of abnormal motor development.

Atypical or delayed motor skills should prompt referral to EI services and, if accessible, to a NICU follow-up clinic or specialty service (such as pediatric neurology) that performs early detection examinations (Table 1). At the 18-month well-child visit, general developmental screening identifies typical motor skills that should be achieved, including ability to sit, stand, walk independently, grasp, and manipulate small objects.

ID occurs in approximately 1.14% to 2.5% of US children27,28  and carries lifelong disability of varying severity. Children who are ultimately diagnosed with mild ID reach medical attention because of family/caregiver appraisal of delayed development, delays identified in developmental screening and surveillance, or teacher appraisal of academic delays. Often the presenting concerns are delayed understanding of language, delayed play or interaction, and the paucity of expressive vocabulary. Children with both language and nonverbal problem solving delays or visual motor and play delays are often diagnosed in early childhood with “developmental delay.” Developmental delay is the slow acquisition of milestones in any one stream of development, whereas global developmental delay is diagnosed when 2 or more streams (domains) of development are delayed.28  A description of global developmental delay is often used in children too young for reliable IQ testing and frequently describes children who later receive a diagnosis of ID. Ultimately, the diagnosis of ID requires documentation of IQ with measures below 70 to 75 and similarly low adaptive functions,76  which can be measured after 3 to 4 years of age and are usually stable after 5 to 7 years of age. It is difficult to assess for ID during infancy. As children age, monitoring and repeated screening for delayed milestone acquisition are most likely to detect manifestations of mild or moderate global delays (Table 1). Recognition of delay should be followed by referral to an EI program, where available, for confirmation and quantification of delay in all developmental domains. Quantification of delay determines eligibility for publicly funded EI services, including child therapies, family/caregiver support, and resource coordination, although eligibility varies across states.77  Developmental evaluations can occur through Individuals with Disabilities Education Act Part C EI services (if child is under age 36 months) and Part B, ideally between 30 to 36 months, to alleviate any gap in services, if a child is transitioning from EI to publicly funded special education. Referral for audiology assessment is imperative for all children with language delay (though it may be difficult to access in some locations), even if a newborn hearing assessment was performed, to ensure that hearing loss is not the underlying cause of language delays.78 

Children who are blind or have severe visual impairment are at increased lifetime risk for developmental delays, frequent hospitalization, socioeconomic problems, and death compared with children with sight.79  As a result of high rates of ROP, in its revised 2018 policy, the AAP recommends that infants born with birth weight ≤1500 g or at <31 weeks’ gestational age receive retinal screening examinations to detect ROP during the NICU stay.80  Children born very preterm, even those without ROP, are 3 to 4 times more likely to have poor visual acuity and nearly 10 times more likely to have strabismus than term-born children. Risks for ocular morbidity decrease but are still higher than the GPP for infants born moderately and late preterm.81 

Much of the risk for visual impairments in infants born preterm does not occur for 1 to 3 years after NICU stays. As part of comprehensive health supervision, PCPs can provide longitudinal developmental surveillance of red flags for visual impairment, including nystagmus or poor tracking of items close to infant’s or child’s face, and evidence of strabismus or low vision during the preschool years (Table 1). Referral to an ophthalmologic specialist is appropriate if the PCP has concerns or at any time if families or caregivers have concerns about their child’s vision.

Hearing loss, defined as bilateral loss >40 dB, occurs in 1% to 2% of screened newborn infants in population studies in North America and European countries.82  Infants admitted to a NICU have a 6.9 times higher rate of hearing loss than those who do not require NICU care.83  In 2007, the AAP, as a member of the Joint Committee on Infant Hearing, endorsed a comprehensive early hearing detection and intervention position statement, including the recommendation that all infants who spend more than 5 days in a NICU receive automated auditory brainstem response screening84  because of their increased risk for hearing loss from bilateral sensorineural or permanent conductive and to include aural neuropathies (which otoacoustic emissions tests cannot detect). One of the best ways to be reassured of intact hearing in infants is to confirm the infant’s appropriate performance on a newborn hearing screen.82  Additionally, the updated 2019 Joint Committee on Infant Hearing and early hearing detection and intervention position statement emphasized the importance of the PCP in reinforcing targeted screening and continuous surveillance for those at-risk, such that all infants have received a newborn screening by 1 month of age, and if the hearing screen is failed, have received assessment by 3 months of age, and if needed, are in EI services by 6 months of age.85  Any preterm infant who demonstrates delayed auditory and/or communication skills development or for whom a caregiver expresses concern, even if the child passed the newborn hearing screening, should receive an audiologic evaluation.78 

Developmental screening and surveillance for ASD in all children is a priority and should not be missed in children with a history of preterm birth. The overall prevalence of ASD is evolving and yet unrefined, particularly in children who were born late- or moderately preterm (thus, not included in Fig 1 or Appendix). Stronger evidence demonstrates a 7% prevalence of ASD86  for children born at <32 weeks’ gestation, compared with an overall prevalence of 1.7% to 1.9% in the United States.27,30  The risk of ASD is also higher in children with a diagnosis of cognitive dysfunction, seizures, or CP.87  The risk for ASD in infants born preterm appears to be most associated with younger gestational ages, lower birth weights, and abnormal neuroimaging.8890  Currently, the AAP recommends screening for ASD in all children at 18 to 24 months of age.24  Screening for ASD should be interpreted carefully in children born at less than 31 weeks’ gestation, because rates of positive screens are very high (21% to 41%) in this population when followed to 2 years of age89,91  and are particularly high in preterm children with motor, cognitive, vision, and hearing deficits.92  Confounding the diagnosis of ASD in children with a history of preterm birth is a common preterm behavioral phenotype that is characterized by difficulty with attention, emotion, peer relations, and social skills. In the absence of cognitive disability, children who were born extremely preterm were 4 times more likely at 10 years of age to have an elevated Social Responsiveness Scale and demonstrate deficits in attention, language, communication, and emotion.93  The overall prevalence of the preterm behavioral phenotype in older children who were born preterm is approximately 20%.94  Positive results on an ASD screener at 18 and 24 months of age, even if the child does not receive a diagnosis of ASD, identifies children with a range of other developmental delays who may benefit from EI services.95 

By 24 to 30 months’ corrected age, the vast majority of children who have NDI associated with severe developmental disabilities will have been identified with signs of delayed or atypical development, CP,72  or cognitive impairment. Severe sensory impairments, such as blindness or severe hearing loss, if present, should have been identified in the first year of life. Children should be walking and running with symmetry and strength by 18 to 24 months’ corrected age. For optimal outcome, growth and head circumference should be approaching age-matched peers.96,97  ASD screening at 18 and 24 months24,98  should guide referral or reassurance. Otherwise, most caregivers are anxiously waiting to be reassured that their child with a history of preterm birth and/or neonatal complications is no longer at risk for severe neurodevelopmental disabilities. PCPs can share growth and developmental progress with caregivers and discuss the receding risks for severe developmental disabilities associated with preterm birth. However, caregivers, educators, and pediatricians need to remain vigilant for high-frequency, lower-severity conditions that present later in preschool years or even at school age.14,71,99  Although also common in the GPP, significantly more children born preterm who have average IQs experience academic underachievement, language and speech disorders, grade retention, developmental coordination disorder, attention deficit/hyperactivity disorder, visual motor integration problems, other visual impairments, internalizing and externalizing behaviors, and poor social interactions.14,71,99  ASD, without ID or language delay, may also present later in childhood. Of note, children whose date of birth and “due date” cross school entry dates may be disadvantaged by starting school a full academic year earlier than they would have if born at term.14  For these children, remembering their perinatal course and monitoring them more frequently during early childhood is prudent.

Preterm birth and its complications have a potent effect on neurodevelopmental outcomes. Immature brains are vulnerable to injury, inflammation, and infection.6,8,13,17,22,23,26,71  Underpinning the perinatal process, and even contributing to disparities of prematurity, are longitudinal and transactional processes attributed to social determinants of health experienced during periods of prenatal and postnatal brain growth and development.100,101  These processes include individual, family, and community factors affecting maternal health and pregnancy, as well as postnatal child experiences with caregivers and the degree to which children are being raised in safe, stable, nurturing, language-rich environments. If children are spared neurodevelopmental impairment associated with effects of perinatal conditions, their overall long-term neurodevelopmental outcome is most strongly associated to early childhood experiences (both positive and negative) and social determinants of health (maternal education, poverty, teenage pregnancy, health disparities attributable to racism, etc).102 

The risk stratification framework (Fig 1) is designed to provide easy decision-making support to PCPs who, in addition to offering preventive care in alignment with Bright Futures: Guidelines for Health Supervision of Infants, Children, and Adolescents (4th Edition) for all children,10  can provide enhanced monitoring in early childhood for children born preterm.26  The framework consolidates extensive contemporary developmental outcome data (Appendix) to inform more individualized developmental surveillance and timely referral for additional assessments or interventions when a patient’s degree of risk for developmental disability is substantial.

All PCPs who care for children born preterm should have access to a consulting neonatologist and/or multidisciplinary high-risk infant follow-up (HRIF) programs.15  Maintaining up-to-date contact with a local neonatology service or local HRIF clinic (where available) and being aware of the program’s criteria to ensure that eligible children in their practice participate in a HRIF program is advised. For many programs around the country, the HRIF program can reciprocally support pediatricians in their patients’ local care coordination as well as provide expertise in clinical management, such as oxygen support, feeding, vaccinations, and specific therapy services.

In addition to maintaining a collaborative relationship with neonatology services and HRIF clinics, PCPs can confidently implement appropriate next steps for ALL children born preterm, which may include:

  • Referral to EI services for eligibility of services. Even when children born preterm are medically stable, EI programs often provide additional supports for caregivers, relational and infant mental health, and other social supports.77 

  • Heightened developmental screening24  and surveillance, as outlined in Fig 2.

  • Discussion with family of developmental risks associated with prematurity and reiteration of conversations that likely occurred during NICU stay but may have been difficult to understand or retain at that time.

For children with increasing degrees of risk for developmental disabilities, additional action by the pediatrician may include:

  • HRIF referral and resources.

  • Timely referral or follow-up to ophthalmology and audiology assessments.

  • Caregiver education about episodes that may be signs of a seizure disorder (to optimize referral to pediatric neurology, if suspected).

  • Referral to physical therapy (for gross motor, coordination concerns), speech-language pathology (feeding, communication concerns), and/or occupational therapy (fine motor, feeding, regulation concerns) to clarify nature of developmental concerns. If a developmental disorder is suspected, further assessment and subspecialty referral may be warranted (such as developmental and behavioral pediatrics, physical medicine and rehabilitation, CP clinic, neurology).

Collaborative relationships with HRIF teams and community providers, such as EI programs, can assist pediatricians in decision-making support, including (1) provision of timely reassurance that severe neurodevelopmental disabilities associated with preterm birth are not present, when appropriate; and (2) the determination when developmental differences cannot be solely attributed to being “born early” and additional etiologies (ie, genetic, social determinants of health) of neurodevelopmental problems should be considered and addressed. Pediatricians are ideally poised to recognize developmental risk factors other than preterm birth, such as pre- and postnatal psychosocial adversity (foster or kinship care, which are recognized markers of prior childhood adversity) and other social determinants of health (such as housing insecurity, teenage parenthood, family and caregiver mental health conditions, or substance use, poverty, food insecurity, families new to the United States, etc) and can provide additional wrap-around care coordination for caregivers, such as financial supports, cultural navigation, transportation, etc.

The PCP’s role in health supervision of infants born preterm entails an enhanced awareness of increased developmental risk factors, consideration of additional mitigators of developmental impairment, including effects of family relational health103  and social determinants of health, and when indicated, confident timely reassurance of the absence of adverse neurodevelopmental outcomes. In keeping with the tenets of family-centered care and the medical home, the use of ongoing developmental surveillance, coordinated care, shared decision-making, strengths-based guidance, and advocacy for appropriate habilitative and rehabilitative services are the premises of trusted care and are consistent with the recommendations of the AAP.10  Benefits of risk awareness based on history of perinatal conditions can empower pediatricians to prioritize healthy development at each and every encounter. Increased awareness coupled with heightened developmental surveillance between routine health supervision and validated screening visits will optimize early identification and referral of at-risk children who demonstrate concerning signs or symptoms of developmental differences. Another benefit of linking perinatal risk awareness to neurodevelopmental outcomes is to prompt clinicians to seek additional information when developmental delays exceed anticipated risks, and require consideration of other etiologies (eg, family and caregiver mental health conditions, genetic or acquired conditions, and social determinants of health). For example, findings of ID should not be dismissively attributed to a child born moderately or late preterm without neonatal complications and should trigger further investigation. Similarly, severe dyskinetic CP is not an expected outcome of a preterm infant with mild BPD. In these cases, when outcomes do not align with risk, etiologic workup (such as referral to pediatric neurology) should be performed as it would for a child without an established risk factor, such as preterm birth or a perinatal condition.

As provider concerns wane, reassurance that severe neurodevelopmental disability is absent in a child born preterm can be invaluable to families. The timeline for developmental reassurance is dictated by developmental milestone acquisition at the typical anticipated rate and sequence, usually when the child is 24 to 30 months’ corrected age. Discussing waning risks for severe developmental disabilities and promoting a strengths-based outlook delivered as developmentally informed, confident reassurance is a gift to caregivers who carry a burden of worry for their children born preterm.104 

The reassurance of the absence of severe neurodevelopmental impairments and the cautious acknowledgment of the continued risk of less-severe, high-frequency neurodevelopmental sequelae is a delicate but necessary balance. Although the majority of preterm infants survive without severe impairments, very few do not have lower-severity morbidities. Language delays, learning disabilities, motor coordination disorders, emotional and behavioral disorders, and social skill deficits are more often recognized in school-aged children with a history of preterm birth than their low-risk, term counterparts.105  Moreover, when several low-severity neurodevelopmental disabilities co-occur, even though mild, the constellation may be functionally impairing. Continued awareness of the risk of these developmental sequelae into school-age years for children with history of preterm birth and/or neonatal complications should prompt pediatricians to recommend community-based assessments and supports, such as consideration for special education, related services, and/or prescribing pediatric therapies.106  Reassessment of hearing and vision may be considered, along with a heightened awareness for other disabilities, such as a seizure disorder. The role of the PCP in the care of children born at risk for neurodevelopmental impairments attributable to preterm birth is a long-term commitment to vigilant surveillance. Some PCPs are finding that children with special health care needs and some children with a history of preterm birth often require more than typical health supervision visits and are adding an extra visit between regularly scheduled visits to specifically address developmental surveillance and family and caregiver concerns.29 

Beth Ellen Davis, MD, MPH, FAAP

Mary O’Connor Leppert, MD, FAAP

Kendell German, MD, FAAP

Christoph U. Lehmann, MD, FAAP

Ira Adams-Chapman, MD, MPH, FAAP

Garey Noritz, MD, FAAP, FACP, Chairperson

Rishi Agrawal, MD, MPH, FAAP

Jessica E. A. Foster, MD, MPH, FAAP

Ellen Fremion, MD, FAAP, FACP

Sheryl Frierson, MD, MEd, FAAP

Michelle Melicosta, MD, MPH, FAAP

Barbara S. Saunders, DO, FAAP

Siddharth Srivastava, MD, FAAP

Christopher Stille, MD, MPH, FAAP

Jilda Vargus-Adams, MD, MSc, FAAP

Katharine Zuckerman, MD, MPH, FAAP

Dennis Z. Kuo, MD, MHS, FAAP, Immediate Past Chairperson

Jeffrey Brosco, MD, PhD, FAAP – Maternal and Child Health Bureau

Jennifer Poon, MD, FAAP – Section on Developmental and Behavioral Pediatrics

Matthew Sadof MD, FAAP – Section on Home Care

Allysa Ware, PhD, MSW – Family Voices

Marshalyn Yeargin-Allsopp, MD, FAAP – Centers for Disease Control and Prevention

Alexandra Kuznetsov

Christoph U. Lehmann, MD, FAAP

Eric Eichenwald, MD, Chairperson

Namasivayam Ambalavanan, MD

Charleta Guillory, MD

Mark Hudak, MD

David Kaufman, MD

Camilia Martin, MD

Ashley Lucke, MD

Margaret Parker, MD

Arun Pramanik, MD

Kelly Wade, MD

Timothy Jancelewicz, MD – AAP Section on Surgery

Michael Narvey, MD – Canadian Pediatric Society

Russell Miller, MD – American College of Obstetricians and Gynecologists

RADM Wanda Barfield, MD, MPH – Centers for Disease Control and Prevention

Lisa Grisham, APRN, NNP-BC – National Association of Neonatal Nurses

Jim Couto, MA

All authors participated in conception, design, drafting, and critical revision of the clinical report and approved the final manuscript as submitted.

Clinical reports from the American Academy of Pediatrics benefit from expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of Pediatrics may not reflect the views of the liaisons or the organizations or government agencies that they represent.

The guidance in this statement does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication.

AAP

American Academy of Pediatrics

BPD

bronchopulmonary dysplasia

EI

early intervention

ELBW

extremely low birth weight

GPP

general pediatric population

HIE

hypoxic-ischemic encephalopathy

HRIF

high-risk infant follow-up

IVH

intraventricular hemorrhage

NEC

necrotizing enterocolitis

NHIS

National Health Interview Survey

PCP

primary care pediatrician

PMA

postmenstrual age

PVL

periventricular leukomalacia

ROP

retinopathy of prematurity

TH

therapeutic hypothermia

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