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Position statement

CPS

Follow-up care of the extremely preterm infant after discharge from the neonatal intensive care unit

Posted: Sep 23, 2022

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Principal author(s)

Leonora Hendson, Paige T. Church, Rudaina Banihani, Canadian Paediatric Society, Fetus and Newborn Committee

Paediatr Child Health 2022 27(6):359–364.

Abstract

The survival of babies born extremely preterm (EP, <28 weeks gestation) has improved over time, and many have good outcomes and quality of life. They remain at risk for health issues, including neurosensory and neurodevelopmental difficulties requiring monitoring by primary physicians, paediatricians, and specialty clinics. This statement reviews potential medical and neurodevelopmental consequences for EP infants in the first 2 years after discharge and provides strategies for counselling, early detection, and intervention. EP-related conditions to assess for early include bronchopulmonary dysplasia or respiratory morbidity, feeding and growth concerns, neurosensory development (vision and hearing), cerebral palsy, and autism spectrum disorder. Correction for gestational age should be used for growth and development until 36 months of age. Integral to quality care of the child born EP is attention to the emotional well-being of parents and caregivers.

Keywords: Autism spectrum disorder; Cerebral palsy; Extremely preterm; Neurodevelopmental outcomes; Neurosensory development

What are the impacts of extreme prematurity?

Advances in neonatal care in recent years have greatly increased infant survival at younger gestational ages (GAs) [1]. In Canada, the survival of extremely preterm (EP) newborns who receive active care and are admitted to a Canadian Neonatal Network (CNN) site is 40% for 22 weeks, 50% for 23 weeks, 73% for 24 weeks, 82% for 25 weeks, 90% for 26 weeks, 93% for 27 weeks, and 95% for 28 weeks [2].

Children born EP experience unique medical complications in the neonatal intensive care unit (NICU). Based on Canadian data, 81% of infants born at ≤24 weeks gestation, 77% at 25 weeks, 70% at 26 weeks, 53% at 27 weeks, and 41% at 28 weeks have a major neonatal morbidity, including one of the following: bronchopulmonary dysplasia (BPD), severe retinopathy of prematurity (ROP), neurological injury (NI), stage 2 or 3 necrotizing enterocolitis (NEC), or late-onset sepsis (LOS) [2]. Among EP infants, 39% born at <25 weeks, 23% at 25 to 26 weeks, and 11% at 27 to 28 weeks are sent home on oxygen. Of all these newborns, 1% have a tracheostomy tube, and 6% born at <25 weeks and 2% born at 25 to 28 weeks are discharged with a gastrostomy tube [2].

The Canadian Neonatal Follow-up Network (CNFUN) is a collaboration of neonatal and perinatal programs, in liaison with CNN, that follows infants born <29 weeks with assessment at 21 months corrected age (CA). Seventeen percent of these infants have a significant neurodevelopmental impairment (NDI), and 28.7% have a mild to moderate NDI (Table 1) [3][4]. Gestational age (GA), sex, outborn status (i.e., born outside of a tertiary centre), illness severity, BPD, NEC, LOS, ROP, NI, and site (i.e., location of the tertiary care NICU) were significantly associated with NDI [4].

This position statement highlights key aspects of the care of the EP graduate up to 2 years CA. Although EP infants are born <28 weeks, CNN/CNFUN data include infants born at 28 weeks, and their information is included.

Table 1. Neurodevelopmental outcomes for infants born <29 weeks (2009/17) at 21 months corrected age by significant versus mild to moderate neurodevelopmental impairment
Impairments Significant NDI % Mild to moderate NDI %
Any Any one of the conditions/domains below 16.7 Any one of the conditions/domains below 28.7
Motor Non-ambulatory CP, GMFCS 3 to 5 1.9 Ambulatory CP, GMFCS 1 or 2 3.4
  Bayley-III Motor Composite <70 6.5 Bayley-III Motor Composite 70 to 84 14.6
Cognitive Bayley-III Cognitive Composite <70 3.6 Bayley-III Cognitive Composite 70 to 84 11.8
Language Bayley-III Language Composite <70 11.7 Bayley-III Language Composite 70 to 84 24.7
Hearing Hearing aid or cochlear implant 2.0 Any sensorineural or mixed hearing impairment 4.2
Vision Bilateral visual impairment 1.0 Unilateral visual impairment 0.2

Data drawn from references 3,5

CP, cerebral palsy; GMFCS, Gross Motor Functional Classification System; NDI, neurodevelopmental impairment

What is recommended follow-up for EP infants?

In 2004, a framework for tertiary care follow-up clinics defined optimal assessments for high-risk infants, identified knowledge gaps, and prioritized research efforts [6]. In Canada, infant categories, timing of visits, standardized protocol of assessments, and the role of community and developmental paediatricians in neonatal/perinatal follow-up programs have also been established for some time [7]. Most Canadian neonatal/perinatal follow-up clinics comprise inter-professional teams who follow children born <29 weeks gestation [4] and provide enhanced developmental surveillance and support. Teams may include the following: neonatologist, paediatrician or developmental paediatrician; nurse or nurse practitioner; occupational therapist, physiotherapist, and speech-language therapist; educational or clinical psychologist and psychometrist; dietitian and social worker; orthoptist, ophthalmologist, and audiologist. Working together, such teams provide longitudinal assessment, early identification and treatment, referral to local resources, and quality assurance. Collaboration and coordination of care among primary physicians, paediatricians, and specialized services at key time points are essential to prevent gaps in care and the duplication of services, and ensure early referral for specialty and rehabilitation services, and access to funding and community resources [8]-[39] (Supplementary checklist).

Why use corrected age?

CA refers to chronological age minus the number of weeks born before 40 weeks gestation, and is the recommended measure before 3 years of age [40] for infants born <37 weeks for growth, development, and respiratory function [41]. Because of delayed maturation of the preterm brain, using chronological age results in diminished scores for preterm-born infants that are most apparent under 3 years and in those born at the earliest GA [42][43]. In this position statement, age references are in CA unless otherwise specified.

What are the health challenges of extreme prematurity?

One recent study found that in Canadian infants born ≤28 weeks, 20% needed assistive technology at home, including oxygen (16%), gavage feeding (4%), gastrostomy or jejunostomy (4%), non-invasive ventilation (0.9%), ileostomy or colostomy (0.8%), and tracheostomy (0.6%) [44]. These infants also had lower GA and birth weight and were more likely to have BPD, LOS, or surgical NEC. Further, re-hospitalization after discharge and up to 18 months CA was 60% among infants with medical complexity, and 29% in those without medical complexity. The most common reasons for re-hospitalization were respiratory or surgical [44].

Prescribed medication use was frequent for infants with medical complexity and those without, including inhaled steroids or bronchodilators (32% versus 16%), antibiotics (20% versus 14%), anti-reflux medication (20% versus 4%), diuretics (6% versus 1%), and anticonvulsants (3% versus 1%) [44]. Almost all these infants required outpatient services (physiatry, home-visiting nurse, dietitian, physiotherapist, occupation therapist, speech therapist, rehabilitation services) [44]. The risk for NDI was twofold higher in infants with medical complexity (OR 2.0, 95% CI 1.7 to 2.5) and almost threefold higher for significant NDI (OR 2.8, 95% CI 2.2 to 3.6) [44].

Nutrition is a key determinant for neonatal survival, growth, and neurodevelopment in infants born EP. At discharge, nutrition plans are individualized based on each infant’s needs. Human milk is preferred, exclusive direct breastfeeding when possible and desired, or expressed breast milk (EBM) [17]. Breastfeeding and EBM should be promoted before admission to NICU when possible, and continue after discharge for short-term benefits (e.g., host defense, gastro-intestinal development, feeding tolerance, optimal nutrition, reduced NEC and ROP risk) and long-term benefits (lower obesity rates, improved blood pressure, decreased insulin resistance, improved neurodevelopmental outcomes), and for maternal health at minimal cost to families [17]. For EP infants, especially those with a history of growth failure and underlying medical conditions, post-discharge preterm formula may be required to increase protein and energy intake [12][13]. The highest rates of catch-up growth and bone mineralization occur in the first few months post-discharge [12][13], but there is no consensus on how long post-discharge formulas should be continued.

Growth, feed intake, and quality of feeding should be assessed at discharge, then closely monitored at expected term and every 2 to 4 weeks after discharge until a trend on an appropriate growth curve is established [12][13]. The Fenton growth chart for preterm infants can be used in the early post-discharge setting [10]. Thereafter, monitoring of growth is measured using the World Health Organisation (WHO) Growth Standards [11]. Predominantly breastfed infants (i.e., >50% of intake), infants with persistent morbidities, and infants recently transitioned to a different type or mode of feeding should be monitored closely [12][13]. Parents should have access to a dietitian and/or lactation consultant, as needed.

Iron supplementation is needed to prevent or treat anemia of prematurity. Infants who are predominantly breastfed should receive an iron supplement of 2 mg/kg/day to 3 mg/kg/day elemental iron for the first year [19]. Infants who are predominantly formula-fed may not require iron supplementation if the formula is high in iron. Formula provides 2 mg/kg/day to 3 mg/kg/day of elemental iron (typical formulas designated for preterm infants contain 10 mg/L to 14 mg/L of iron) [19].

Infants who are born EP are at high risk of developing metabolic bone disease of prematurity needing supplementation in the NICU [45][46]. Infants who are exclusively or partially breastfed or formula-fed should receive a minimum of 400 IU/day vitamin D, and up to 800IU/day vitamin D when they are considered high risk (i.e., have darker skin pigmentation or live in northern communities) [20]. 

Paediatric feeding disorder (i.e., when oral intake is inappropriate for age and associated with a medical, nutritional, feeding skill, or psychosocial dysfunction) is common in infants born EP. Feeding disorder may be caused or complicated by BPD, vocal fold paralysis, NI, or adverse feeding experiences [47]. Feeding is a complex ongoing physiologic and behavioural achievement, and feeding skills continue to develop after discharge from the NICU. The WHO framework of International Classification of Functioning, Disability, and Health addresses four feeding domains (medical, nutritional, feeding skill, and/or psychosocial) to better define the needs of patients and families. Relevant specialty clinics and rehabilitative services may be needed to manage and support the parent-infant relationship [47][48].

What are the developmental challenges of extreme prematurity?

Significant NDIs are increased in EP children (Table 1) [3][4]. Much more common, however, are difficulties with emotional and behavioural regulation, and rates of cognitive, motor, and language delay, which increase as GA decreases [3].

Central to the neurodevelopmental presentation with EP birth are variations in critical aspects of brain development resulting from stresses of transition and the extrauterine environment. Despite attempts to optimize environment and minimize risk for injury, brain development for the EP infant continues to be characterized by dysmaturation. Behavioural phenotypes describe cognitive, motor, and social strengths and difficulties observed in a population with a common biological disorder. The behavioural phenotype of the EP infant and toddler is characterized by socio-emotional immaturity, lability, busy behaviour, language challenges, and atypical and delayed motor development [49]. Global developmental delay (at least 2 standard deviations (SDs) below mean) in two or more domains (motor, language, cognition, social/personal, activities of daily living) should be considered in children born EP. Early diagnosis is important to initiate supportive rehabilitative management and community services [27]. 

Cerebral palsy (CP) is a common physical disability that refers to a heterogeneous presentation characterized by impairments in motor function that limit activity. CP is caused by a disturbance to the developing fetal or infant brain [22]. Preterm infants are at higher risk for CP, which is typically associated with severe intraventricular hemorrhage (IVH) or periventricular white matter injury [23][26]. CP is confirmed in 6.2% of children born ≤28 weeks at 21 months CA [3], with risk increasing as GA decreases: 14.8% at 23 weeks, 10.2% at 24 weeks, 7.2% at 25 weeks, 5.6% at 26 weeks, and 4.8% at 27 and 28 weeks [3]. These rates compare with a CP rate of 0.2% to 0.3% in the general population in Canada [23].

Early signs of CP include hand preference, stiffness or tightness in the legs, inability to sit by 9 months, persistent fisting of hands beyond 4 months, and delayed or asymmetrical movement [23]. Diagnosis before 6 months CA is accurate when supported by neuroimaging and standardized neurological assessments administered through neonatal/perinatal follow-up clinics [24]. Timing is important because early interventions (such as constraint-induced movement therapy), and early detection of associated impairments (such as hip surveillance) are known to improve functional outcomes and enhance parent/caregiver well-being [24][25]. Recommended resources are often locally available through inter-professional neonatal/perinatal and specialized CP clinics.

Autism spectrum disorder (ASD) is characterized by impaired social communication, restricted interests, and repetitive patterns of behaviour. There is a four times higher prevalence of ASD among EP children compared with term children [50][51]. As with CP, risk for ASD increases with decreasing GA: an estimated 15.0% at 23 to 24 weeks, 6.5% for 25 to 26 weeks, and 3.4% for 27 weeks [51].

Early behavioural symptoms (language delay, lack of response to name, limited eye contact, repetitive or unusual play) may indicate risk for ASD [28]. Children can be diagnosed with ASD by 2 years of age [28], but screening the EP child for ASD is challenging because sensorimotor and cognitive impairments, and emotional/behavioural dysregulation can confound the diagnosis of [52], or be co-morbid with, ASD.

Three approaches are recommended for diagnosis: involving an experienced and trained sole paediatric care provider, a shared care model, and a team-based approach [53]. For the EP child presenting with ASD, neonatal/perinatal follow-up clinics should provide access to specialized assessment or referral (e.g., a psychologist), or be able to administer diagnostic tools. Neonatal/perinatal follow-up clinics may be able to assist with definitive diagnosis, identify co-morbidities, and determine the child’s overall level of adaptive functioning. Interventions for toddlers include behavioural and developmental approaches with support from therapists, mental health care professionals, and community service providers [54].

Visual impairment due to sequelae of severe ROP or (less often) cerebral visual impairment, is an important yet uncommon outcome in EP infants (Table 1) [3][32][33]. EP infants should have ongoing ophthalmological evaluation for refractive errors, amblyopia, and strabismus [32]. Hearing impairment can also affect EP infants (Table 1) [3]. Auditory neuropathy dys-synchrony has a higher prevalence in children born EP, requiring specific protocols for newborn hearing screening. Infants born EP require ongoing audiology evaluations for late-onset or progressive hearing loss [34][35].

What is the role of early intervention?

The short-term improvements arising from early intervention relate to the plasticity of the developing brain, which is highly adaptive and responsive to environmental stimulation [21]. Such responsiveness provides an opportunity for early, positive interventions.

The developing brain is also vulnerable to negative inputs, including stress, inflammation, pain, and malnutrition. Injurious events can have multiple developmental trajectories, depending on their timing, nature, and mode of recovery. A severe injury can be widespread, leaving no room for recovery. Mild and moderate injuries can have minimal impact, with observable recovery, but sometimes with a relapse after a period of apparent recovery (called a “sleeper effect”). The extent of injury only becomes apparent when the injured area becomes developmentally relevant [49]. This lag time may explain some evidence that the efficacy of early intervention may be limited over the longer term, and relate more to function than diagnosis. For example, early intervention does not alter the diagnosis of CP, but timely therapy is known to positively impact functionality in the child with CP [23][25]. There is clear evidence that early identification and intervention supports children living with ASD [54].

What is the impact on families of a child born EP?

Close attention to the emotional well-being of parents and caregivers is central to quality care. Rates of postnatal depression, post-traumatic stress disorder, and anxiety are significantly higher for parents of preterm children, and are estimated to range between 30% and 60% [8][9]. A parent is the infant’s primary regulator: setting the rhythms for feeding and sleeping, nurturing attachment, and providing family relationships and behaviours that are essential for healthy child development. Screening a parent’s mental health should be considered when they have had a child in the NICU [8][9]. Screening tools such as the Edinburgh Postnatal Depression Scale (EPDS) can be found online, or referral can be made to local perinatal mental health programs. Physicians and other health care providers can engage and build relationships with the families they see by assessing and assisting early relationships at home, and connecting families of children born EP with community resources and supportive services.  

Recommendations

  • Children born extremely preterm (EP) should have access to primary physicians with expertise in longitudinal screening, surveillance, and managed care for growth and nutrition, feeding, respiratory issues, developmental problems, and neurosensory needs. This level and range of care is best provided in association with interprofessional health care teams through neonatal/perinatal follow-up clinics, at key time points. Coordinating care includes early referral to specialty and rehabilitation services, accessing funding, and connecting families with community resources.  
  • Corrected age should be used to measure progress and assess development until a child born EP is at least 3 years of age. Immunizations should be based on chronological age.
  • Nutrition plans for the infant born EP should be individualized, with mother’s milk being the option preferred, and supplemented with formula as needed following discharge from hospital. Mothers should receive guidance and support for breastfeeding and expressing breast milk before, during, and after their stay in the NICU. Iron supplementation should continue for at least 1 year CA in infants who are predominantly breastfed. Infants who are exclusively or partially breastfed or formula-fed should receive vitamin D: 400IU/day, and up to 800IU/day if high risk (i.e., have darker skin or live in northern communities).
  • The diagnosis of cerebral palsy (CP) should be made as early as possible, such that infants can receive early intervention to optimize neuroplasticity and prevent complications. Neuroimaging and early standardized assessments for CP should be available for infants born EP.
  • Infants born EP should receive an early focused evaluation for autism spectrum disorder to determine need for further assessment, detect common co-morbid conditions, and plan treatment. 

Acknowledgements

This position statement has been reviewed by the Community Paediatrics and Nutrition and Gastroenterology Committees of the Canadian Paediatric Society (CPS). It was also reviewed by the CPS Neonatal-Perinatal Medicine Section Executive and the Canadian Premature Babies Foundation (CPBF).

CANADIAN PAEDIATRIC SOCIETY FETUS AND NEWBORN COMMITTEE (2020-2021)

Members: Gabriel Altit MD, Nicole Anderson MD (Resident Member), Heidi Budden MD (Board Representative), Leonora Hendson MD (past member), Souvik Mitra MD, Michael R. Narvey MD (Chair), Eugene Ng MD, Nicole Radziminski MD, Vibhuti Shah MD (past member)

Liaisons: Radha Chari MD (The Society of Obstetricians and Gynaecologists of Canada), James Cummings MD (Committee on Fetus and Newborn, American Academy of Pediatrics), William Ehman MD (College of Family Physicians of Canada), Danica Hamilton RN (Canadian Association of Neonatal Nurses), Chloë Joynt MD (CPS Neonatal-Perinatal Medicine Section Executive), Chantal Nelson PhD (Public Health Agency of Canada)

Principal authors: Leonora Hendson MD, Paige T. Church MD, Rudaina Banihani MD

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Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated: Feb 8, 2024

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