Development of the Premature Infant: Through the Lens of the Pediatrician and Neonatologist Mark Bergeron, MD, MPH Associate Director, Neonatal Medicine and Neonatal Developmental Follow-up Clinic Children’s Hospitals and Clinics of Minnesota – St. Paul Assistant Professor, Pediatrics University of Minnesota Medical School 2011 Strong Foundations Conference

Objectives Discuss prematurity as public health issue –Review morbidity and mortality data Highlight infant health issues resulting from prematurity Understand the impact of prematurity on infant/child development –Brain injury and impairment Provide an overview of short- and long- term measures to address developmental issues

What is Preterm? Term: ≥ 37 weeks postmenstrual age Late Preterm: weeks Moderately Preterm: weeks Very Preterm: weeks Extremely Preterm < 28 weeks

Preterm Birth Statistics Data: PeriStats, March of Dimes Photo: Children’s Hospitals and Clinics of Minnesota

Cost of Preterm Birth. Data: PeriStats, March of Dimes Photo: Children’s Hospitals and Clinics of Minnesota

The First Hurdle: Survival Survival is inversely proportional to gestational age: –“Later is better!” Data: Children’s Hospitals and Clinics of Minnesota

Survival by Gestational Age

The Second Hurdle: “Meaningful” Survival Data: Children’s Hospitals and Clinics of Minnesota

Health Problems Associated with Prematurity Heart and circulation Lung function Breathing Feeding and Digestion Lack of weight gain Brain hemorrhages Immature immune system

Informed Consent to Treat: “NICU Alphabet Soup” PDA- Patent Ductus Arteriosis (heart) NEC- Necrotizing Enterocolitis (digestive) ROP- Retinopathy of Prematurity (eyes) RDS- Respiratory Distress Syndrome (lungs) CLD- Chronic Lung Disease (lungs) PVL- Periventricular Leukomalacia (brain) IVH- Intraventricular Hemorrhage (brain)

Intraventricular Hemorrhage (IVH): A Marker for Developmental Problems Data: Children’s Hospitals and Clinics of Minnesota

The Impact of Prematurity Serious implications for parents, health care team: –Survival is NOT a given –Risk of poor developmental outcome must be weighed carefully when making medical decisions Fundamental Question: What does prematurity mean for the baby’s developmental potential?

Variables that affect the premature infant’s developmental trajectory: Gestational age Birth weight Incidence/severity of lung disease Time spent on mechanical ventilation Need for oxygen White matter brain injury (IVH, PVL) Overall length of time in the NICU Weight gain

Neurodevelopmental Issues in the Preterm Infant

Brain growth in fetal life and infancy During specific times in gestation, different types of cells increase and mature structurally Almost all neurons are present by weeks gestation (good and bad news) The cells that perform basic thinking and control functions of the brain are in place The total number of neurons increase only slightly, glial cells increase until 2 years of age Myelination continues until 4 years of age (longer?) Synaptic rearrangements occur for years

Brain growth in the last trimester Growth of the cerebellum: muscles and coordination of movement Pattern of dendritic connections between neurons –Cerebellum is one of the most vulnerable areas for preemies because it has a spurt of growth at weeks gestation and is complete by 12 months of age –When born prematurely, the dendritic connections are developing under different circumstances where nutrition and metabolic are key

Brain Injury in infancy Fetuses and neonates are uniquely vulnerable to brain injury Decreased oxygen supply Increased oxygen supply Decreased blood flow Bleeding Infection Toxins Radiologic(?)

Brain Injury: Intraventricular Hemorrhage (IVH) ssf pediatriceducation.org

Brain Injury: Periventricular Leukomalacia (PVL) radiologyassistant.nl

Preterm Brain Injury: Long Term Effects Motor –Hypotonia (initially) –Hypertonia Cerebral palsy –Spastic diplegia –Delays Gross Fine Cognitive –Delays –MR Speech/Language –Delays Expressive Receptive

Physiological Regulation and Development Preterm birth is a tremendous physiological stress –Uterus vs. NICU incubator The preterm infant is developmentally unprepared for the change from the intrauterine environment –Sights _ Sounds –Smells _ Pain Response to stimulation is altered –Preemies have instability of respiratory, heart rates and temperature which become learned responses to stimulation

Mitigating Factors - NICU Family-centered care –Encourage family presence and involvement Kangaroo care Developmentally- appropriate environment –Sound –Light –Temperature

Family-centered NICU Care Video: "NICU: the Garden of Hope"

Long-term Follow-up: A Multidisciplinary Approach Primary care provider –Well baby care Routine developmental assessments Home health nursing Local programming –Early Intervention Specialty care –i.e. pulmonology NICU Follow-up Clinic –Scheduled developmental assessment Bayley Scales of Infant Rossetti Infant – Toddler Language Scale Wechsler Preschool and Primary Scale of Intelligence - Revised

NICU Follow-up Clinic Referral Criteria Children’s – St. Paul Birthweight ≤ 1500g ≤ 30 weeks GA > 48 hrs mechanical ventilation Seizures Neurologic abnormality Grade 3-4 IVH BPD IUGR Congenital infection Exchange transfusion Therapeutic hypothermia for HIE Other –Neonatologists’ discretion

NICU Follow-up Clinic Team Pediatric Nurse Practitioner Occupational Therapist Developmental Psychologist Speech/Language Pathologist Neonatologist

Developmental Expectations Chronologic vs. “Adjusted” age? –Developmental milestones and growth parameters should be benchmarked against norms corrected for prematurity. i.e. subtract the “weeks or months born early” from chronological age. –Example: Now 6 m.o. infant born at 32 weeks (2 months preterm): 6 months. – 2 months = 4 months corrected age

Developmental Expectations, continued Conventionally, adjusted age is utilized until 24 months in clinical settings –Developmental testing –NICU Follow-up clinic Practically, adjusted age remains useful –Early Intervention (many preemies eligible until age 3) –Decisions regarding preschool and kindergarten readiness Physical Cognitive Emotional

Learning Behaviors-Special Considerations When development is measured early on, former preemies may not do as well due to greater difficulty focusing attention on task completion –Altered learning patterns? Altered response to stress/stimulation May need more repetitive play to learn skills Special risks –ADHD –Autism spectrum disorders (controversial)

Summary Preterm birth remains an important public health issue As extreme preterm birth-related mortality has decreased, morbidity, especially neurologic, has increased Much has been done to support premature infants’ developmental needs, both in the short- and long-term

Resources American Academy of Pediatrics – American Academy of Pediatrics Section on Perinatal Pediatrics – March of Dimes – Children’s Hospitals and Clinics of Minnesota Neonatal Cornerstone Program – Associates in Newborn Medicine, P.A. – Minnesota Perinatal Organization and Minnesota Prematurity Coalition –

Questions/Comments Mark Bergeron: