Description

Neonatal intensive care unit (NICU) graduates (former premature infants), who have an increased risk for neurodevelopmental disabilities (NDD), require close follow-up and serial cognitive, sensory, and motor monitoring.

Epidemiology

• In the United States, 78 of 1,000 births are admitted to NICUs; admission rates increase with decreasing gestational age (GA).
• Prematurity: In 2016, the U.S. preterm birth rate increased for the 1st time in 8 years to 9.6%.
• Hypoxic ischemic encephalopathy (HIE): 1 to 3/1,000 births should be admitted to the NICU within 6 hours for therapeutic hypothermia.
• Respiratory failure: deficiency of oxygenation with insufficient ventilation; mechanical ventilation required in 18/1,000 births; associated with many comorbidities and up to 15% mortality
• Congenital anomalies (3% of U.S. births) account for 20% infant deaths; most common is congenital heart disease (CHD) in 1%; neural tube defects in 3 to 4/10,000; genetic syndromes

Risk Factors

• Prematurity—deficits generally correlate with GA, birth weight (BW); preterm birth associated with injuries to many organ systems due to:
  • Factors that precipitate preterm delivery (infection, inflammation)
  • Physiologic instability after birth
  • Required use of immature organ systems
  • Insufficient endogenous protective factors (thyroxin, cortisol, surfactant)
  • Side effects of treatment
• Brain injury—intraventricular hemorrhage (IVH), HIE, stroke, encephalomalacia, periventricular leukomalacia (PVL), hydrocephalus, seizures
• Congenital/postnatal infections—CMV, HSV, HIV, bacterial sepsis, Zika virus
• Congenital anomalies increase risk for later NDD.
• CHD: higher rates of brain malformations, microcephaly, prolonged hypoxemia with cardiopulmonary bypass/arrest
• Neonatal abstinence syndrome—higher risk with polydrug exposure
• Respiratory failure/chronic lung disease (CLD) intermittent hypoxia and acidosis; poor growth
• Intrauterine growth restriction (IUGR)
• Genetic syndromes
• Severe neonatal illness—sepsis, necrotizing enterocolitis (NEC, especially requiring surgery), retinopathy of prematurity (ROP, grades 4 to 5)

History

• BW, GA, NICU complications
• Neuroimaging
• Length of intubation and oxygen need
• Receipt of ototoxic medications
• Umbilical lines—umbilical venous and arterial lines increase risk for hypertension secondary to renal artery or vein stenosis/thrombosis.
• Discharge medications with weaning plans
• Feeding plan

Physical Exam

• Vital signs (including blood pressures)
• Growth parameters—height, weight, head circumferences (especially in children with history of hydrocephalus/shunts; lack of head growth concerning as well as rapid growth)
• General physical examination focusing on muscle tone and motor function

Diagnostic Tests and Interpretation

• Regular American Academy of Pediatrics (AAP) developmental screening
  • Clinicians should not watch and wait when delay is suspected for these high-risk children.
• NICU follow-up clinics should perform detailed cognitive and motor assessments.
• Use age corrected for degree of prematurity (corrected age) when assessing preterm infants until at least 2 years chronologic age.

General Measures

• Prompt referral to early intervention programs for infants and toddlers (Part C of the Individuals with Disabilities Education Act [IDEA])
• Individualized family service plan (IFSP, before 3 years), individualized education plan (IEP)/504 Plan between ages 4 and 7 years of age
• Continue close follow-up for at 2 years (even if the child does not qualify for NICU clinic) due to risk for ongoing school and learning problems.
• Home visits/home nursing: if available, can improve motor development index and interactions between parents and infant

Follow-Up Recommendations

• Cerebral palsy (CP):
  • Definition: nonprogressive motor coordination and planning disorder due to injury or malformation of developing brain
  • Risk factors for CP: IUGR, sepsis, surgery, high-frequency ventilation, postnatal steroids, abnormal neonatal neuroimaging (white matter injury, ventriculomegaly, severe IVH, bilateral cystic, PVL), HIE, GA
  • CP rates increase with decreasing GA.
    • Full term 0.1%
    • 34 to 36 weeks 0.3%
    • 31 to 33 weeks 2%
    • 28 to 30 weeks ~5%
    • 23 to 27 weeks ~5–15%
    • <25 weeks 10–30%
  • Rates of CP in HIE: ~20–30%
  • Most common type in preterm infants is spastic diplegia.
• Minor neuromotor dysfunction
  • Definition: mild motor impairments such as early marked hand preference, overflow movements, poor handwriting, visuospatial, and sensorimotor integration problems
  • Preterm children at increased risk
  • Can also adversely affect child’s self-help skills and self-esteem
• Intellectual disability
  • Defined as performance >2 SDs below mean on intelligence + adaptive function tests
  • Increases with decreasing GA
    • ~10% children born at GA <32 weeks
    • Up to 40–50% in children born at GA <26 weeks
  • Higher rates with neuroimaging abnormalities (severe IVH, hydrocephalus, white matter injury)
  • Prematurity generally shifts IQ baseline down by 10 points; IQ scores decrease by 1 to 2 points for every week <33 weeks.
  • Strongly affected by environment (parental education, socioeconomic status), genetics
• Visual impairment
  • Most common causes of pediatric visual impairment in the United States: cortical visual impairment (CVI), ROP, optic nerve hypoplasia
  • 37% of significant visual impairments in children attributable to prematurity
  • CVI—often underdiagnosed visual processing disorder; associated with occipital cortex injury; improves with specific visual/educational interventions
  • ROP—presents at 32 weeks, peaks at 38 to 40 weeks, regresses at 46 weeks
  • 84% of children born at GA <28 weeks have some degree of ROP; 40% of those born at <26 weeks require laser surgery.
  • Can lead to retinal detachment/blindness
  • Other visual problems: reduced visual acuity, amblyopia, strabismus, myopia
  • Follow-up eye exam at 12 months corrected for degree of prematurity if GA <32 weeks
• Hearing impairment
  • 10- to 20-fold higher among NICU infants versus term infants; higher risk with prolonged oxygen use
    • ~3% mild to moderately severe hearing loss
    • ~2% profound loss
  • Sensorineural hearing loss most common
    • 1/2 congenital; 1/2 acquired (i.e., due to gentamicin, furosemide), ECMO (up to 37%), CNS disease, craniofacial defects
  • If high risk, recheck hearing every 6 months for 3 years, as hearing loss onset delayed (previously normal ABR) in 10%; 28% have progressive loss between tests.
  • Early identification/treatment (American Sign Language, hearing aids, cochlear implants) critical for language development
• Language
  • Preterm infants have high risk of language delay and language-based learning disability.
  • 1st year: problems with early speech perception/auditory discrimination (i.e., discriminate native vs. non-native phonemes); fewer vocalizations; delay in babbling, less phonologic complexity, smaller receptive lexicon
  • 12 to 24 months—smaller expressive lexicon
• Behavioral spectrum
  • ADHD-like behaviors are 2 to 6 times higher in premature infants; more often correlating with inattention and slower processing
  • Increased risk for comorbid internalizing disorders (anxiety, depression)
  • Poorer social and communication skills
  • Autism rate higher: 4–8% in children born at GA <28 weeks
  • Important to keep in mind that premature children have higher rates of false positives on screens due to co-occurring brain injury, sensory, or neurodevelopmental impairments
• Executive function
  • Definition: cognitive control used to plan and organize approach to tasks
  • Former preterm children have lower scores on visual and working memory, cognitive flexibility, sustained attention, response inhibition, fluency, and planning.
• Specific learning disabilities (SLD)
  • Definition: low scores on tests of reading, writing, spelling, mathematics in setting of normal IQ, adequate education
  • Higher rates in preterm children for math (highest), reading, and spelling, most in GAs <31 weeks but present in late preterm
  • ELBW rates of ~20–60% for each type SLD versus general population rates ~5–15%
  • Higher rates of SLD and special education use with moderate to severe HIE, respiratory failure, IUGR, congenital infections
• Osteopenia of prematurity
  • Increased risk with low GA, prolonged IV nutrition, long-term ventilation, furosemide, steroids, antibiotics, anticonvulsants
  • The AAP recommends all breast/formula-fed infants with <1,000 mL of vitamin D-fortified milk per day should be supplemented with 400 IU vitamin D daily; premature babies may need up to 1,000 IU daily.
  • Elevations of alkaline phosphatase >650 U/L—consider adding calcium, phosphorus.
• Anemia of prematurity
  • Preterm infants have low iron stores at birth, high requirements due to rapid growth rates.
  • Iron is important for brain development (synapse function and brain myelination).
  • 2 mg/kg/24 h of iron until 1 year corrected; formula-fed babies get in iron in formula, breastfed babies should be supplemented.
  • Preterm infants have earlier and lower physiologic nadir, with hemoglobin (HgB) 6 to 7 mg/dL at 3 to 7 weeks of age versus term babies—HgB 9 to 10 mg/dL at 6 to 8 weeks of age
  • Iron deficiency anemia occurs earlier, check HgB every 6 months; if <11 mg/dL after nadir, increase supplementation to 3 to 5 mg/kg/24 h.
• Feeding challenges
  • Integration of sucking, swallowing, and breathing can be delayed in preterm infants (later than 33 to 36 weeks postmenstrual age).
  • Late preterm infants—poorer state organization, sleepier, latch challenges
  • The risk of poor feeding outcomes increases with medical problems (CLD, NEC).
  • High rates of feeding problems at 2 years in infants with BW <1,000 g; up to 33% may need gastrostomy.
• Seizures
  • Follow-up with neurologist; drug blood level within 1 month of discharge
  • Seizures in neonatal period do not necessarily predict later childhood seizures but predict increased risk of NDD.
• Dental
  • Premature infants should be seen within 18 months—increased risk for enamel hypoplasia/discoloration, intubation can affect alveolar ridge/palate
• Parental stress
  • NICU parents have high rates of perinatal mood disorders including postpartum depression, post traumatic stress disorder (PTSD), anxiety disorders, obsessive-compulsive disorders (OCD).
  • All have been shown to affect children’s developmental trajectory.

Diet

• Preterm formula:
  • Provides increased protein, calcium, phosphorus, zinc, vitamins, trace elements
  • Preterm (vs. term) formula increases 12- to 18-month weight, length, head circumference.
  • Typically, continue premature fortified human milk/preterm formula at minimum 22 kcal/oz until 12 months for infants born <28 weeks GA; consider term formula at 6 to 9 months if good growth.
• No consensus on the length of time milk should be fortified
  • Goals: all feeds taken orally, growing well, no nutritional deficiencies (alkaline phosphatase, calcium/phosphorus, albumin normal)

Patient Teaching

• Frequent tummy time (2 to 3 times a day for at least 5 minutes) on a firm surface while awake
• Safe sleep recommendations
  • “Back to sleep”
  • Remove soft bedding, blankets, toys, pillows, and bumper pads out of baby’s sleep area.
  • Room sharing, but not bed sharing, is recommended.
• Avoid standing activities until infant pulls to stand on furniture.
• Hand toys to each hand even if the child has a preference.
• Talking and reading to the infant

ICD-9

• V67.9 Unspecified follow-up examination
• V67.59 Other follow-up examination

ICD-10

Z09 Encounter for follow-up examination after completed treatment for conditions other than malignant neoplasm

SNOMED

• 185389009 Follow-up visit
• 281036007 Follow-up consultation
• 390906007 Follow-up encounter