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Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors

Long-term neurodevelopmental impairment in infants born preterm: Epidemiology and risk factors
Literature review current through: May 2024.
This topic last updated: May 29, 2024.

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

The epidemiology and risk factors for long-term NDI among survivors of preterm birth will be reviewed here. Issues related to follow-up care for preterm infants, including neurodevelopmental surveillance and early intervention, are discussed separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention" and "Care of the neonatal intensive care unit graduate".)

Other outcomes (mortality, short-term complications, and other long-term complications) 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".)

DEFINITIONS

Preterm birth — Degrees of preterm birth are typically defined by birth weight (BW) or gestational age (GA); 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. (See "Intellectual disability (ID) in children: Clinical features, evaluation, and diagnosis", section on 'Assessment of infants and young children'.)

Moderate to severe cerebral palsy (CP) defined as a score of ≥2 on the Gross Motor Function Classification System (GMFCS). (See "Cerebral palsy: Classification and clinical features", section on 'Functional classification systems'.)

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).

In addition, behavioral, psychological, and functional outcomes are increasingly being recognized as important long-term neurodevelopmental outcomes and will be discussed within this review. Outcomes in early childhood are often reported in the context of corrected or postmenstrual age, which can be derived from a calculator (calculator 1).

LIMITATIONS OF THE DATA — Interpretation of the neonatal outcomes literature is challenging because of differences in clinical practice (particularly in providing active treatment for periviable infants), study design (study population, evaluation tools, and outcomes measured), and changes in perinatal care over time. The challenge was illustrated in an analysis of three systematic reviews, which identified 107 different cohorts, but the individual studies varied considerably such that only eight cohorts were included in all three reviews [1].

Differences in study design

Study population – Differences in defining the study population make it challenging to compare data from different studies.

Birth weight (BW) classification versus gestational age (GA) can be problematic, as the population may include relatively more mature infants with intrauterine growth retardation (IUGR) within a given BW category. Outcome results may be impacted if there are a significant number of patients with IUGR because these infants have a greater risk of neonatal morbidities and poorer outcomes compared with their appropriate gestational age (AGA) counterparts, but typically have better outcomes compared with more preterm infants at equivalent BW [2,3] (see "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns"). As dating techniques have improved, GA classifications have become predominant. Although GA groupings may allow for inclusion of large and small for GA infants in the same group, groups defined by this method are more likely to be at similar embryologic/fetal development stages than classification based on BW. As a result, GA classification is more commonly used in reporting of long-term outcome of preterm infants.

Outborn versus inborn infants – Morbidity and mortality appear to be worse for preterm infants born at a center without a tertiary neonatal intensive care unit (NICU) requiring neonatal transport compared with inborn infants who do not require transfer [4-6]. In particular, infants with physiological instability during transport are at risk for significant neurodevelopmental impairment (NDI) and mortality [7]. Therefore, the mix of inborn and outborn infants between studies may impact on survival and long-term outcome.

Definitions of outcome measures – Differing definitions of outcome, particularly the definition of severe NDI, alter results [8,9]. This was illustrated in an analysis of the database for preterm infants (GA 23 to 28 weeks) from the Canadian Neonatal Follow-up Network that reported the incidence of severe NDI ranged from 3.5 to 14.9 percent depending on the definition used for severe NDI [8]. (See 'Definitions' above.)

Evaluation methods – There is variability in the evaluation tools used to assess outcomes in studies and results may not be directly comparable. For example, several studies have shown that results from the third edition of Bayley Scales of Infant Development (BSID III, 2006) resulted in higher cognitive scores than the 2nd edition (1992) [10-13]. The available data suggest that a cutoff of <85 on the cognitive score on BSID III is comparable to a cutoff of <70 on the former Bayley II MDII [14-16]. The former cutoff is used in the contemporary definition of moderate to severe NDI. (See 'Definitions' above.)

The fourth edition of the BSID was released in September 2019 and uses reporting methods consistent with the BSID III but with a different reference group. To date, there are no studies that compare the Bayley IV with previous versions in assessing preterm survivors. Additional details regarding these and other tools are provided separately. (See "Intellectual disability (ID) in children: Clinical features, evaluation, and diagnosis", section on 'Assessment of infants and young children'.)

Subsequent confounding factors – Subsequent factors that may affect neurodevelopmental development and school readiness include sociodemographic factors (eg, maternal education), household income (eg, Medicaid insurance as a marker of poverty), ongoing health issues, and participation in early intervention programs. The presence of these factors may vary, making it challenging to compare results from different studies. (See "School readiness for children in the United States", section on 'Factors related to a child's ability to learn'.)

Impact of improved survival — For extremely preterm (EPT; GA <28 weeks) infants, overall survival has improved dramatically as result of improved perinatal and neonatal care [17]. However, survival without NDI among EPT infants has not improved at the same pace as overall survival. This is because many surviving infants, particularly those at the limits of viability, have neurodevelopmental sequelae.

Data are inconsistent regarding whether neurodevelopmental outcomes for preterm infants have improved with advances in perinatal care. Some studies reported improved neurodevelopmental outcomes in later era cohorts (eg, infants born after 2005) compared with earlier cohorts (eg, infants born in the 1990s) [18-26], others did not find a difference [27,28]. Conflicting results may be explained by differences in GA, as discussed below. (See 'Risk of NDI by gestational age' below.)

Changes in practice over time — Observed changes in practices over time are felt to be major contributors to both improved neonatal survival and possibly neurodevelopmental outcome [17-21,29-31]. As a result, comparisons between birth cohort eras should be interpreted with caution. This is of particular importance when comparing adult prematurity outcomes with more recent birth cohorts because management of an EPT infant in the modern era is considerably different compared with an infant born in the 1990s.

In addition, there are variations in outcome across regions that persist after adjusting for known population, maternal, and infant factors [32,33]. Further work is needed to understand the impact of practice variation and regional disparities on outcomes.

Active treatment for periviable infants — Periviability refers to the earliest stage of fetal maturity wherein there is reasonable, though not high, chance of extrauterine survival (generally defined as GA between 22 and <26 weeks). There are global and regional differences in the level of initial care provided to periviable infants [34-37]. These differences in clinical practice impact survival neurodevelopmental outcomes (table 2A-B). As a result, it is challenging to compare survival and neurodevelopmental outcomes from studies that may differ in their approach to resuscitation for periviable infants and to interpret these data as it applies to individual patients. (See "Periviable birth (limit of viability)", section on 'Outcomes'.)

Issues regarding interpreting the data for periviable infants are discussed in greater detail separately. (See "Periviable birth (limit of viability)", section on 'Limitations of the data'.)

Specific interventions — Advances in perinatal and neonatal care have improved outcomes for preterm infants either directly or indirectly (by reducing associated complications such as periventricular-intraventricular hemorrhage [PIVH]). Examples include:

Antenatal corticosteroid therapy, which is associated with reduced need for mechanical ventilation, reduced rates of risk of severe PIVH, and improved survival without NDI, including reduced rates of moderate to severe cerebral palsy (CP) [38-41]. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on 'Evidence of efficacy'.)

Limiting postnatal corticosteroid therapy, which may impact neurodevelopmental outcome [42-49]. The long-term effect of postnatal use of corticosteroid therapy is discussed in greater detail separately. (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

Advances in neonatal ventilation, particularly increased use of noninvasive modalities (eg, continuous positive airway pressure [cPAP]), which has improved survival and reduced morbidity (eg, bronchopulmonary dysplasia [BPD], severe PIVH, and pulmonary air leak), which may impact neurodevelopmental outcome. (See 'Comorbid conditions' below and "Overview of mechanical ventilation in neonates" and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome", section on 'Long-term neurodevelopmental outcomes' and "Pulmonary air leak in the newborn" and "Bronchopulmonary dysplasia (BPD): Management and outcome", section on 'Neurodevelopmental outcomes'.)

Surfactant, which has been associated with increased survival, especially for extremely preterm infants. However, surfactant therapy has not been directly associated with improved neurodevelopment outcome. (See "Respiratory distress syndrome (RDS) in preterm infants: Management".)

Antenatal magnesium sulfate, which has been associated with decreased risk of CP and severe motor dysfunction. Clinical trials have shown that preterm infants whose mothers receive magnesium sulfate have a lower risk of CP and severe motor dysfunction compared with nonexposed infants. (See "Neuroprotective effects of in utero exposure to magnesium sulfate", section on 'Evidence of efficacy from randomized trials and meta-analyses'.)

RISK OF NDI BY GESTATIONAL AGE — The risk of NDI increases with decreasing gestational age (GA) and birth weight (BW) [38,50-60].

The following sections review neurodevelopmental outcomes for survivors based on GA categories.

Periviable infants — Neurodevelopmental outcomes for infants born between 22 to 25 weeks GA are summarized in the table (table 2B) and discussed detail separately. (See "Periviable birth (limit of viability)", section on 'Neurodevelopmental outcome'.)

Extremely preterm infant — Among extremely preterm (EPT; GA <28 weeks) and/or extremely low birth weight (ELBW; birth weight <1000 g) infants, the likelihood of surviving without NDI decreases with decreasing GA (table 2B). For EPT survivors, impairments in cognition, motor function, vision, and/or hearing are common, may be severe, and can persist into school age and adulthood [61]. (See 'Outcomes in adulthood' below.)

The following is a summary of the outcomes we discuss with parents and care providers of EPT infants based upon the available literature. As noted above, synthesizing the information is challenging due to differences in study design and differences between older and more recent birth cohorts. (See 'Limitations of the data' above.)

Major disability – Approximately 15 to 25 percent of surviving EPT infants have major disability (ie, severe NDI), defined as any of the following, when evaluated at 18 to 24 months corrected age; the relative frequencies for each type of disability are as follows [17,25,26,62]:

Significant cognitive and/or motor impairment (ie, a score >2 standard deviations below the mean on a standardized test) – 10 to 15 percent

Cerebral palsy (CP) - 6 to 12 percent

Hearing loss requiring amplification devices – 1 to 3 percent

Blindness – 1 to 2 percent

Infants with severe NDI at 18 to 24 months are likely to have persistent disability throughout childhood [63], however, some may have improvement in cognitive function [64]. Infants with milder disability are more likely to improve as they age.

Neurodevelopmental outcome is assessed more accurately at school age than in early childhood because there may be cognitive recovery over time as the brain continues to develop and/or the assessment tools used at two years of life are not as accurate in assessing cognition [63,65,66]. In one cohort of 802 surviving EPT infants born between 2002 and 2004, neurodevelopmental status at age 10 years improved in 27 percent, worsened in 5 percent, and remained unchanged in 67 percent compared with assessments performed at age 2 years [64]. Of note, one-third of individuals who were initially classified as having severe NDI improved to a milder degree of disability by age 10 years. Other studies evaluating EPT survivors at school age (ie, 6 to 10 years of age) reported rates of severe NDI ranging from 13 to 21 percent [63,67-69].

The estimates presented above are based upon data from cohorts of EPT infants born after 2005. Earlier cohorts reported higher rates of major disability (as high as 30 percent) [25,26].

Less severe disability – Milder disabilities are more common than severe disability. In a prospective cohort study of 486 surviving EPT infants born between 2004 to 2007 who were evaluated at 6.5 years of age, 36 percent had no disability, 30 percent had mild disability, 20 percent had moderate disability, and 13 percent had severe disability [69]. In another study of 1021 surviving EPT infants, 10 percent were diagnosed with CP by age five years [70]. Among children without a diagnosis of CP, 32 percent were found to have mild motor abnormalities on standardized testing, including difficulties with balance, manual dexterity, and aiming and catching.

Learning disability and need for specialized educational intervention and services – Children born EPT are more likely to have learning difficulties in reading and mathematics and have lower teacher ratings [71-74]. These children often need additional educational intervention and special services [72,75].

Adult outcome – Data on adult outcomes for EPT infants are limited. In one report of a birth cohort from 1995, 60 percent of individuals at nineteen years of age had at least one impairment in general cognitive functioning and visuomotor abilities, and a third had deficits in four or more domains [76]. Cognitive impairment was observed in 45 percent of EPT adults compared with 3 percent of controls. (See 'Outcomes in adulthood' below.)

Very preterm infant — The risk of severe NDI among very preterm (VPT, GA 28 to <32 weeks) or very low birth weight (VLBW) infants (BW <1500 g) infants is less than that of EPT or ELBW survivors. However, approximately 30 to 40 percent of VPT infants have some degree of NDI [26,75,77-84]. The findings in studies of VLBW infants may differ because the relative proportion of ELBW patients within each cohort varies. (See 'Differences in study design' above.)

In a prospective cohort of 441 VPT infants born in 1997, 36 percent had neurodevelopmental disabilities and 30 percent used special healthcare resources (eg, physiotherapy, speech therapy, occupational therapy, psychologist, and psychiatrist) at five years of age [75]. Even children without moderate or severe neurologic disabilities at discharge remained at risk for global developmental delay and discrepancies in academic achievement compared with full-term controls [77,78]. Risk factors for impaired outcome included lower GA at birth, presence of cerebral lesions on brain imaging, being born with intrauterine growth failure, lack of breastfeeding, and low parental socioeconomic status. In a subsequent cohort of infants born in 2011, 4.2 percent of infants born at 27 to 31 weeks of gestation had cerebral palsy (CP) and 41 percent had developmental delay at two years of age [26].

In a meta-analysis of individual participant data from eight birth cohorts of 2135 adults, individuals who were born very preterm or very low birth weight had lower intelligence quotient (IQ) scores than those born at term [85]. After adjusting for sex, maternal education, and excluding those with neurosensory impairment, mean IQ Z-scores were -0.65 standard deviation (95% CI -0.76 to -0.55 SD), which is equivalent to 9.8 IQ points. Other studies have reported VPT school-age children have poorer scores in memory and are more likely to have academic difficulties than those children born at term [60,83,86].

Moderate to late preterm infants — Moderate (GA between 32 and 33 6/7 weeks) and late preterm infants (GA between 34 and less than 37 weeks) are more likely to have long-term neurodevelopmental impairment compared with full-term infants [87]. Children born moderately preterm appear to be particularly at increased risk for cerebral palsy and global developmental delay [88]. In a meta-analysis of 76 studies from mostly high income countries, the prevalence of CP in children born moderately preterm, late preterm, and at term was 17, 3, 0.5 per 1000, respectively [88]. The prevalence of global developmental delay was 350, 132, and 66 per 1000, respectively.

Longitudinal international studies of moderate to late preterm infants have also reported the following neurodevelopmental impairment based on age at assessment [88-97]:

Two years of age – Poor cognitive testing, neuropsychological functioning and neurosensory impairment [89,97,98].

Preschool – Developmental delay at preschool age based on parent report [91].

School age – Not school ready, poor cognitive testing, need for special educational services, and lower than expected grade level achievement on academic test or in teacher assessments [88,93,94,99,100].

A more complete discussion on the long-term neurodevelopmental outcome of late preterm infants (GA between 34 and 36 weeks) is presented separately. (See "Late preterm infants", section on 'Neurodevelopmental outcome'.)

RISK FACTORS FOR NDI — As discussed in the previous section, gestational age (GA) is one of the most important factors in determining risk of NDI in preterm infants.

Additional risk factors include male sex, twin pregnancy, congenital malformations, comorbid neonatal conditions, socioeconomic factors, and lack of adequate antenatal care [54,84,85,101,102]. These are summarized in the following sections. The approach to assessing risk of NDI in preterm infants is discussed in greater detail separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Identifying at-risk infants' and "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Tools'.)

Environmental factors — Although the association between preterm birth and NDI is well established, far less is known about the role of environment and experience in moderating the association. Several studies have reported that certain environmental factors (eg, higher maternal education level, parental interventions, home environment, daycare environment) have beneficial effects on cognition, speech, and language development [103-108]. Similarly, adverse early childhood experiences may negatively impact neurodevelopmental outcomes. In particular, there is an increased risk for cognitive delay at two years of age for infants who are discharged from the hospital with child protection service supervision [109].

Studies evaluating neurodevelopmental outcomes in preterm infants often attempt to control for some of these confounding factors (particularly maternal education level); however, it may be challenging to adequately control for all relevant environmental variables. (See 'Limitations of the data' above.)

Comorbid conditions — The risk of NDI is increased in preterm infants who have any of the following comorbidities:

Bronchopulmonary dysplasia (BPD) [62,110,111].

In addition, postnatal use of glucocorticoids to treat BPD is associated with an increased risk of cerebral palsy (CP). (See "Postnatal use of glucocorticoids for prevention of bronchopulmonary dysplasia (BPD) in preterm infants".)

Perinatal infections, including [62,112,113]:

Maternal intra-amniotic infection (clinical chorioamnionitis) (see "Clinical chorioamnionitis", section on 'Neurodevelopmental impairment')

Necrotizing enterocolitis (NEC) (see "Neonatal necrotizing enterocolitis: Management and prognosis", section on 'Long-term sequelae')

Sepsis (see "Treatment and prevention of bacterial sepsis in preterm infants <34 weeks gestation", section on 'Morbidity')

Meningitis (see "Bacterial meningitis in the neonate: Treatment and outcome", section on 'Outcome')

Retinopathy of prematurity (ROP). (See "Retinopathy of prematurity (ROP): Risk factors, classification, and screening".)

Intraventricular hemorrhage (IVH). (See "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Management and outcome", section on 'Outcome'.)

Fetal growth restriction. (See "Fetal growth restriction (FGR) and small for gestational age (SGA) newborns", section on 'Neurodevelopmental impairment (NDI)'.)

Poor postnatal growth – In very preterm infants, growth impairment, including poor head growth, has been associated with impaired cognitive and motor performance [114-116]. In extremely low birth weight (ELBW) infants, better weight gain during neonatal intensive care unit (NICU) hospitalization is associated with reduced risk of CP and better scores on cognitive testing at 18 to 22 months corrected age [117]. In contrast, greater weight loss and delay in regain of birthweight in such infants are associated with lower scores on cognitive and motor testing at 24 months corrected age, respectively [118].

Congenital anomalies – Preterm survivors with congenital anomalies are more likely to have a cognitive impairment and motor and neurosensory deficits [119].

Twin gestation for ELBW infants [120]. Similar data on higher order gestation are not available.

Surgical procedures during birth hospitalization [121].

Maternal comorbidities may also affect the risk of NDI. As an example, in extremely preterm infants, exposure to maternal hypertension has been associated with increased risk of NDI at 24 months postmenstrual age, and this risk is heightened in those who are also small for gestational age (SGA) [122].

Care factors — The risk of NDI is increased in preterm infants born to mothers without adequate prenatal and perinatal care (eg, lack of antenatal corticosteroids). (See 'Specific interventions' above.)

OTHER NEURODEVELOPMENTAL SEQUELAE

Structural brain injury — Preterm survivors with severe neonatal brain injury, defined as abnormalities detected by head ultrasound, have the most severe neurodevelopment impairment (eg, requiring additional school services and major disability with motor, cognitive, or neurosensory impairments [such as CP]) [123-126]. Neonatal brain injury may also be associated with increased risk for psychiatric disorders (eg, major depression and obsessive-compulsive disorder [OCD]) in adolescence [127].

Subsequent structural brain changes in former preterm infants have been documented by magnetic resonance imaging (MRI) at school age, adolescence, and adulthood. These include thinning of the corpus callosum, decreased brain volume, increased ventricular volume, and abnormal white matter development [128-139]. In MRI studies comparing term versus very preterm children, preterm birth was associated with white matter and cortical thickness reductions at 0, 7, and 13 years of age [138,139]. These alterations were associated with motor, language, and memory function.

Additional details about the prognostic value of neuroimaging in preterm survivors are provided separately. (See "Long-term neurodevelopmental impairment in infants born preterm: Risk assessment, follow-up care, and early intervention", section on 'Neuroimaging'.)

Speech and language delays — Speech and language impairments are common among preterm survivors, with risk and severity inversely proportional to GA. Delays may be observed in acquisition of expressive and/or receptive language, and articulation [11,103,140-142]. There is evidence of partial preterm catch-up in speech language functions compared with term controls, which increases with environmental factors such as maternal level of education [103,104]. Language outcomes are related to cognitive function, hearing, prenatal and postnatal socioeconomic status, environment, ethnicity, and structural changes at the level of the larynx related to prior intubation [142-145]. (See "Evaluation and treatment of speech and language disorders in children".)

Behavioral and mental health problems — Children who were born preterm, especially those who were extremely or very preterm, are more likely than children born full term to have behavioral and mental health problems [146].

Extremely preterm and very preterm infants – Children who are born extremely or very preterm are more likely than children who were born at term to have behavioral and emotional problems. A study from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network of extremely preterm infants (gestational age <27 weeks) born between 2008 and 2012 reported one-third of the cohort had behavioral problems and one-quarter had deficits in socioemotional competence at 18 to 22 months corrected age [147]. Sociodemographic factors (eg, mothers with less than a high school education and lower maternal age) and deficits in cognitive and language function increase the risk of problems in behavior and socioemotional competence. However, preterm adolescent and young adult survivors tend to engage in less risky behavior and be shier than those born full term [148-152].

The following behavioral and emotional problems are more commonly observed in children and adolescents who were born extremely or very preterm compared with peers who were born full term.

Difficulties in attention [148,152-162].

Poor peer interaction [149,156-158,162,163].

Hyperactivity [152,154-157,159-161,164].

Emotional and conduct problems, including anxiety, depression, being withdrawn, and somatic complaints [148,152-154,156-158,160,161,165,166].

Autism spectrum disorders [160,167-169].

Psychiatric disorders [165,170,171].

Moderate to late preterm infants – Although data are limited, moderate to late preterm infants at preschool age are at increased risk of behavioral and emotional problems, including attention deficit hyperactivity disorder and autism spectrum disorder, compared with peers born at term based on parental assessment [88,169,172-175].

Functional disabilities — School-age children who were extremely or very preterm have a greater risk for functional disabilities that impact on completing daily activities and quality of life compared with peers born at term. These may be subtle deficits that include problems with motor coordination (developmental coordination disorder, also referred to as noncerebral palsy motor impairment) [176,177], social interactive skills, and executive function (working memory, problem-solving, planning, and organization) [80,99,162,178-182]. The risk for functional disabilities increases with decreasing gestational age (GA) and is reported to occur in 40 percent of children born before 26 weeks gestation [71,80]. Compared with peers born at term, children born moderate to late preterm also appear to have a higher risk of visual and hearing impairment, although the latter appear be more statistically significant in those born at 37 to 38 weeks gestation [88]. In some affected individuals, these deficits may contribute to academic, motor, and behavioral outcomes. (See "Developmental coordination disorder: Clinical features and diagnosis".)

OUTCOMES IN ADULTHOOD

Disabilities — In former preterm infants, the risk of adulthood medical and social disabilities increases with decreasing gestational age (GA).

Several studies have reported lower rates of educational achievement, independent living, lower net income, and permanent employment in preterm adult survivors compared with those born full term [183-188]. These results are most likely due to poor cognitive skills leading to impaired learning, especially in adults with birth weights (BW) below 1500 g or GA below 32 weeks, and increased risk of medical disabilities (cerebral palsy [CP], psychiatric and behavioral disorders, and physical disability) [183,189-191]. Higher socioeconomic status appears to decrease the effect of GA upon cognitive test scores [189].

In contrast, other studies suggest that despite their increased risk of neurodevelopmental disability, adults who were born preterm may overcome these difficulties and become functional young adults at a comparable rate to those who were born full term. These studies report similar rates of high school graduation, pursuit of postsecondary education, employment, independent living, marriage, and parenthood [192,193]. Differences in outcome among these studies have been attributed to higher socioeconomic status of the study population, an increase in educational support, or benefit from a national healthcare system [194].

Quality of life — Young adults who were born preterm and their parents report a greater prevalence and complexity of functional limitations than controls born at term and their parents/caregivers [195]. Longitudinal studies have reported that individuals born very preterm have lower health-related quality of life based on assessment using the Health Utility Index Mark 3 questionnaire [195-198]. In one systemic review of the literature, adults born preterm were less likely to experience romantic and sexual partnerships and parenting [199]. Nevertheless, in several studies, preterm adults and their families report a satisfactory quality of life similar to those who are born at term [200-204].

In addition, patients and their parents have a better perception of their quality of life than healthcare professionals [205]. As a result, it is important for healthcare providers to be aware of this discrepancy so that they do not only focus narrowly on neurodevelopmental disabilities of their patients but broaden their consideration of outcome to include the ability of adult survivors to overcome their limitations with a positive self-perception of their quality of life [192,206,207].

SUMMARY AND RECOMMENDATIONS

Definition – Neurodevelopmental impairment (NDI) is a composite term that includes cognitive, motor, sensory, behavioral, and/or psychologic impairments. Outcomes in early childhood are reported in the context of corrected or postmenstrual age (calculator 1). (See 'Definitions' above.)

Severe NDI is generally defined as having any of the following:

Significant cognitive and/or motor impairment (ie, a score >2 standard deviations below the mean on a standardized test)

Cerebral palsy (CP)

Hearing loss requiring amplification devices

Blindness

Risk of NDI in preterm infants – Individuals born preterm are at increased risk for NDI compared with those born at term. The risk of NDI increases with decreasing gestational age (GA) (see 'Risk of NDI by gestational age' above):

Periviable infants (GA 22 to 25 weeks) – Neurodevelopmental outcomes for infants born between 22 to 25 weeks GA are summarized in the table (table 2B) and discussed detail separately. (See "Periviable birth (limit of viability)", section on 'Neurodevelopmental outcome'.)

Extremely preterm infants (EPT, GA <28 weeks) – For EPT survivors, NDI is common, may be severe, and can persist into school age and adulthood. Severe disability is seen in approximately 15 to 25 percent of surviving EPT infants; mild to moderate disability is seen in an additional 40 to 50 percent. (See 'Extremely preterm infant' above.)

Very preterm infants (VPT, GA 28 to <32 weeks) – Approximately 30 to 40 percent of VPT infants have some degree of NDI; however, severe NDI is less common in VPT infants compared with EPT infants. (See 'Very preterm infant' above.)

Moderate (GA between 32 and 33 6/7 weeks) and late preterm infants (GA between 34 and less than 37 weeks) – Infants in these categories are more likely to have long-term NDI compared with full-term infants. Severe NDI is more common when there are other risk factors. (See 'Moderate to late preterm infants' above and "Late preterm infants", section on 'Neurodevelopmental outcome'.)

Risk factors for NDI – Risk factors for NDI include GA, twin pregnancy, male sex, congenital malformations, comorbid neonatal conditions, socioeconomic factors, and lack of adequate antenatal care. (See 'Risk factors for NDI' above.)

Other neurodevelopmental sequelae – In addition to the disabilities discussed above, individuals born preterm commonly experience the following problems (see 'Other neurodevelopmental sequelae' above):

Speech and language delays, including delays in acquisition of expressive and/or receptive language, and articulation. (See 'Speech and language delays' above.)

Behavioral and emotional problems, including attention deficit hyperactivity disorder (ADHD), difficulty in peer interactions, general anxiety and depression, and autism spectrum disorder. (See 'Behavioral and mental health problems' above.)

Functional disabilities, including problems of motor coordination, social skills, and executive function that impact managing daily activities. (See 'Functional disabilities' above.)

Outcomes in adulthood – Adults who were born preterm are more likely to have medical and social disabilities compared with those born full term. Nevertheless, many report that they have a satisfactory quality of life similar to those who were born at term. (See 'Outcomes in adulthood' above.)

Limitations of the data – Interpretation of data on long-term outcomes in preterm infants is challenging because of differences in clinical practice (particularly in providing active treatment for periviable infants), study design (study population, evaluation tools, and outcomes measured), and changes in perinatal care over time. These factors should be considered when using the data to inform decision-making in clinical practice. (See 'Limitations of the data' above.)

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

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Topic 4967 Version 99.0

References

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