Follow-Up of NICU Graduates
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.
- 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
- 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)
- BW, GA, NICU complications
- 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
- 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.
- Use same chronologic age as term infants.
- See American Academy of Pediatrics (AAP) Guidelines for LBW/preterm infants.
- Palivizumab—use based on AAP guidelines.
- 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
- 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
- 10- to 20-fold higher among NICU infants versus term infants; higher risk with prolonged oxygen use
- 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.
- 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.
- 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.
- 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)
- 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
- Allen MC, Cristofalo E, Kim C. Outcomes of preterm infants: morbidity replaces mortality. Clin Perinatol. 2011;38: 441–454. [PMID:21890018]
- Andrews B, Pellerite M, Myers P, et al. NICU follow-up: medical and developmental management age 0 to 3 years. NeoReviews. 2014;15:e123–e132.
- Browne JV, Ross ES. Eating as a neurodevelopmental process for high-risk newborns. Clin Perinatol. 2011;38(4):731–743. [PMID:22107901]
- de Vries L, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010;95(3):F220–F224. [PMID:20444814]
- Doyle LW, Anderson PJ, Battin M, et al. Long term follow up of high risk children: who, why and how? BMC Pediatr. 2014;14:279. [PMID:25399544]
- Johnson S, Marlow N. Growing up after extremely preterm birth: lifespan mental health outcomes. Semin Fetal Neonatal Med. 2014;19(2):97–104. [PMID:24290907]
- Mahle WT, Wernovsky G. Long-term developmental outcome of children with complex congenital heart disease. Clin Perinatol. 2001;28(1):235–247. [PMID:11265509]
- Repka MX. Ophthalmological problems of the premature infant. Ment Retard Dev Disabil Res Rev. 2002;8(4):249–257. [PMID:12454901]
- Robertson CM, Howarth TM, Bork DL, et al. Permanent bilateral sensory and neural hearing loss of children after neonatal intensive care because of extreme prematurity: a thirty-year study. Pediatrics. 2009;123(5):e797–e807. [PMID:19403472]
- V67.9 Unspecified follow-up examination
- V67.59 Other follow-up examination
Z09 Encounter for follow-up examination after completed treatment for conditions other than malignant neoplasm
- 185389009 Follow-up visit
- 281036007 Follow-up consultation
- 390906007 Follow-up encounter
- Q: What growth curves should we use for tracking NICU graduates?
- A: Fenton growth curves accurately reflect intrauterine accretion and are used in NICU but are poorer for children >36 weeks GA. WHO growth charts are best adjusted for age once 4 to 8 weeks postterm.
- Monitor growth every 1 to 2 weeks for 2 months; continue close monitoring if the child’s growth is ≤3%, if that child has chronic disease, or is falling off curve.
- Q: How long do I account for “catch up” growth for a premature infant?
- A: For any baby born <32 weeks, corrections for GA should be made for weight up to 24 months of age, stature to 40 months of age, and head circumference to 18 months of age. Poor gains in head circumference in first 8 months after birth indicate poor long-term outcomes.
Rebecca A. Dorner, MD
Vera Joanna Burton, MD, PhD
Marilee C. Allen, MD
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