Complications of Prematurity

Jenny Wilson, MD
Pediatric neurology
Developmental Evaluation Clinic
(formally NICU follow-up clinic) at OHSU

wilsjen@ohsu.edu

5/1/2014
 Outline
Definitions
Overview of epidemiology/outcomes
Common NICU complications, by organ system
Common medical concerns after discharge
 Definitions

Late Preterm
(34-36 +6 weeks)

Tucker & McGuire. Epidemiology of Preterm Birth. BMJ 2004.

 Definitions
Classification Birthweight
Low Birthweight (LBW) < 2500 grams
Very Low Birthweight < 1500 grams
(VLBW)
Extremely Low < 1000 grams
Birthweight (ELBW)
 Epidemiology
Preterm delivery affects 11.5% of pregnancies
in the United States
Survival
 Mortality & Morbidity

Fanaroff, et al. Trends in Neonatal Morbidity & Mortality for Very Low Birthweight Infants. AJOG
2007.
Neonatal Intensive Care Unit (NICU)
Complications By Organ System
The Lungs
 Respiratory Distress Syndrome (RDS)
Gas exchange occurs in the alveoli
Surfactant, a detergent, keeps the alveoli open
by decreasing surface tension.
Surfactant deficiency results in collapse of the
alveoli
Surfactant is not produced well before 30-32
weeks
Surfactant deficiency results in respiratory
failure (RDS)
 Respiratory Distress Syndrome (RDS)
Occurs in 10%, increasing with
decreasing gestational age
A leading cause of
morbidity/mortality in
premature babies
Treatment:
Prenatal: steroids
Postnatal:
Surfactant replacement therapy
Respiratory support (mechanical
ventilation)
 Bronchopulmonary Dysplasia (BPD)
also known as Chronic Lung Disease (CLD)
Abnormal alveolar formation/injury in premies
who had RDS, from mechanical ventilation/high
oxygen concentration
Defined as requiring oxygen at 36 weeks post-
conceptual age
 BPD
Symptoms:
Increased work of breathing
Oxygen requirement
Growth failure
Can result in pulmonary hypertension and heart
failure

Treatment:
- Respiratory support
- Diuretics
- Bronchodilators (albuterol), inhaled steroids
- Systemic steroids (though worsens
neurodevelopmental outcomes)
- Maximize nutrition (often have high caloric needs)
 Apnea of Prematurity
Premature infants may stop breathing for 20
seconds or more, may be followed by drop in
heart rate and oxygen saturation
May be treated with caffeine
Typically, but not always, resolves by term
The Heart
 Patent Ductus Arteriosus (PDA)
In fetal life, the ductus shunts
blood away from the lungs and to
the body (placenta does the job
of the lungs)
The ductus closes within 48 hours
of birth
- Premature babies are at high risk of the ductus not
closing (PDA)- occurs in 30% of VLBW infants
- This can result in worsening of pulmonary function,
higher rates of BPD , IVH and NEC, heart failure
- Treatment: conservative, indomethacin, or surgical
ligation
Gastrointestinal
 Necrotizing enterocolitis (NEC)
Bacterial infection of intestines leading to inflammation
& necrosis
Occurs in 6-7% of VLBW infants
Presents with feeding intolerance, blood in stools,
apnea, and other nonspecific signs.
Can result in bowel perforation, septic shock
Management:
Medical: antibiotics, supportive
Surgical: resection with ostomy placement or placement of
peritoneal drain
Complications: death (20-30%), stricture formation,
short gut syndrome (9%), frequent/loose stools,
impaired growth, worse neurodevelopmental outcome
The Eyes
 Retinopathy of Prematurity (ROP)

Retinal blood vessels are sensitive to

stress, which can cause them to stop
growing
When they start growing again it is
abnormal, excessive growth called
ROP
Eyes need to be examined until
retina are completely vascularized
Abnormal vessels may regress, or
can progress to retinal detachment,
vision loss
Treated with laser ablation if severe
 The Brain

24
weeks
 Intraventricular Hemorrhage
(IVH)
Bleeding in the periventricular germinal matrix (a
layer of neuronal precursor cells)
Classification (Grades)
I: germinal matrix hemorrhage
II: IVH without ventricular dilation
III: IVH with ventricular dilation
IV: IVH with parenchymal involvement
Treatment:
Supportive
Shunting for hydrocephalus
 IVH and Neurodevelopmental
Outcomes
Grades I-II:
Developmental delay: 8%,
Cerebral palsy: 10.5%
Grades III-IV
Developmental delay: 17.5%
Cerebral palsy: 30%
 Periventricular
Leukomalacia (PVL)
Necrosis of periventricular white
matter resulting from cerebral
hypoperfusion and
oligodendrocyte vulnerability
Ocurs in 6% of VLBW babies on
ultrasound.
More than half of patients with
cystic PVL develop cerebral palsy,
classically spastic diplegia
(affecting the lower extremities)
 Discharge
Most premies are discharged when they reach
term
Parents typically asked to stay 1-2 nights with
their baby in the hospital
Many have significant ongoing medical needs
after discharge
First clinic visit within one week of discharge
Need a pediatrician able to care for the
complicated needs of a premie
 Monitoring
Growth
Vaccinations
Palivizumab (Synagis) in high-risk infants
Hearing
Vision
Development
Respiratory
Parental/social concerns
Safety: higher rates of SIDS in premature babies
 Which baby is safest?
A B

C D E
Lungs/Respiratory
 BPD: after discharge
Infants with BPD - 50% higher rates of
rehospitalization in the first year after
Higher rates of respiratory infections
Higher rates of asthma
Higher caloric needs
30% to 65% of infants with BPD experience growth
failure soon after initial hospital discharge.
 BPD: Management
May be on oxygen, diuretics, albuterol
Will often need follow-up with pulmonology
Monitor
Respiratory status
Growth/nutrition (may need 25% more calories)
Electrolytes, if on diuretics
Sometimes cardiac monitoring
Typically becomes less problematic after the first
two years.
 The Heart: after discharge
Infants with BPD at risk for pulmonary
hypertension and right heart failure
At higher risk for later
Hypertension
already at school age, BP higher in premature children
Extreme prematurity (2327 weeks) associated with a
2.5-fold increased rate of BP medication in young
adulthood compared with full-term birth.
Cardiovascular disease
Type 2 diabetes
 Anemia
Term babies have a dip in hemoglobin
(physiologic anemia) at 8-12 weeks
Premature babies have more severe anemia
The AAP recommendation is to treat
premature and LBW infants with iron, if
breastfed
 Gastroesophageal Reflux
Reflux is common in premature infants
If causes morbidity, called GERD
(D=disease)
Discomfort during/after feeds
Respiratory difficulties
Failure to thrive
If the above symptoms are present, treat:
Change feeding frequency/positioning
Medication: H2 blockers (raniditine) or PPI (omeprazole)
Rarely, jejunal feeding or surgery (nissen fundoplication)
Often resolves by one year
 Vision
Preterm infants at higher risk for vision
problems:
Decreased acuity 27%
Strabismus 13-25%
Astigmatism 11% (at 5 years of age)
Severe visual impairment or blindness: 12%
(2627 weeks), 48% (< 25 weeks)
36% of ELBW adolescents wear glasses
Premature babies need regular eye exams
after discharge
 Hydrocephalus
Build-up of fluid in the ventricles
causing increased pressure
25% of babies with IVH develop
hydrocephalus
May require ongoing monitoring
after discharge
Monitor head circumference
Signs of increased ICP
Bulging fontanelle
Vomiting
Lethargy
May require ventriculoperitoneal
shunt (VPS) placement.
 Neurodevelopment: Case
4 year-old boy who was born at 25 weeks,
twin pregnancy. PDA, RDS, ROP.
At 4 years:
Expressive language disorder (childhood apraxia of
speech) requiring 3 x/wk speech therapy
Developmental coordination disorder
Strabismus s/p two eye surgeries, wears glasses
and has some difficulties with judging distances
Mild cognitive disability
Some inattention/hyperactivity
 Who is at risk for abnormal
neurodevelopmental outcomes?
Higher risk with increasing prematurity,
decreasing BW
IVH, particularly grades III-IV
Shunted hydrocephalus
PVL or other brain injury
BPD, ROP
 Who is at risk for abnormal
neurodevelopmental outcomes?
Environment:
One study found that 45% of
medicaid-insured premies had
language delay compared with
8% of privately insured at ~2
yrs (Wild et al. Early Hum Dev. 2013)
Another study found that
preterm infants spoken to more
in the NICU had better Hart and Risley, Education Review 2004.
cognitive/language outcomes
at 7 and 18 months (Caskey et al.
Pediatrics 2014)
 Developmental Delays

More than 1.5 SD below the mean or 25% below

chronologic age in one or more of the following areas:
physical, cognitive, communication, social or emotional, or
adaptive development
Correct for prematurity until around 2 years of age
https://www.vtoxford.org/research/elbw/calc/readme.aspx
(google: elbw calculator)
Ages and Stages Questionnaire
 Approach for the delayed child?
Environmental enrichment:
Teach families to talk to their babies, use lots of
language, sing/music
Tummy time, opportunities to be mobile
Age-appropriate toys
Referral to early intervention
Have hearing and vision been checked?
Refer to developmental specialist
 Cerebral Palsy
Disorder of movement or posture as a result of
non-progressive injury in the developing brain
While all premature babies are at risk, those
with PVL and higher grade IVH (III-IV) are at
highest risk.
Early in infancy they may be hypotonic
Delayed motor milestones
May have asymmetric reaching at 4-6 months
Posturing, spasticity, clonus develops
Diagnosis often reached between 1-2 years,
sometimes later
 Cerebral Palsy
Treatment:
Manage symptoms of increased muscle tone
(medications, botox, orthopedic surgery)
Provide services: PT, OT
Services for children with disabilities mandated for
children under 21 years.
Children 0-3 years eligible for early intervention
Provide equipment: AFOs, walkers, wheelchairs,
wrist splints, assistive technology, etc.
Provide support/resources
 Other Deficits
Developmental coordination disorder
Mild gross motor delays and difficulties with
coordination
Fine motor deficits
Language disorders
Cognitive deficits
 Hearing
6% of 6-year-olds born before 26 weeks gestation
were wearing hearing aids, and another 4% had
mild hearing loss
 Behavioral, etc.
ADHD
Academic issues, learning disabilities
72% of adolescents with a BW <750 grams had school
difficulties).
Psychological: anxiety and depression
Autism spectrum disorder
Higher rates among preterm children
Consider if lack of expressive language, decreased eye
contact, no pointing, no joint attention
Autism screening questionnaires: M-CHAT is free online
Formal diagnosis done in Autism Clinic or by a trained
psychologist using Autism Diagnostic Observation Schedule
(ADOS).
Treatment: Applied Behavior Analysis (ABA)
https://www.m-chat.org/_references/mchatDOTorg.pdf
 Psychosocial
Psychosocial distress highest for parents of VLBW infants
during the first month of life, persisting during the first two
years of life.
Higher effect with low income families with less education
and more severely disabled children

Vulnerable child syndrome:

Parents:
Overprotective, separation anxiety, are unable to set limits, have
excessive concerns about their childs health, overuse medical services
Children:
Sleep disorders, school problems, behavior problems.
Treatment:
uncovering the source of the parents anxiety and re-educating them
about their childs health, regular visits with PMD, may need therapy
 Summary
Prematurity is common, and has high
morbidity and mortality
All organ systems are vulnerable to
complications of prematurity
Premature babies often need closer
monitoring after discharge and have higher
health care needs/utilization
 References
Ritu Chitkara, MD
Tucker & McGuire. Epidemiology of Preterm Birth. BMJ 2004.
Saigal et al. An overview of mortality and sequelae of preterm birth from infancy to adulthood. Vol 371 January 19,
2008
Fanaroff, et al. Trends in Neonatal Morbidity & Mortality for Very Low Birthweight Infants. AJOG 2007.
William Engle. Surfactant-Replacement Therapy for Respiratory Distress in the Preterm and Term Neonate. Pediatrics
Vol. 121 No. 2 February 1, 2008 pp. 419 -432 .
Kair et al. Bronchopulmonary Dysplasia. Pediatrics in Review. 2012;33;255
UpToDate
Bolisetty et al. Intraventricular hemorrhage and Neurodevelopmental Outcomes in Extremely Preterm Infants.
Pediatrics 2014;133;55
Carter et al. Infants in a neonatal intensive care unit: parental response. Arch Dis Child Fetal Neonatal Ed 2005;90
Howell and Graham. Parents Experiences of Neonatal Care. Nov 2011. Picker Institute Europe.
Doyle LW, Faber B, Callanan C, Morley R. Blood pressure in late adolescence and very low birth weight. Pediatrics 2003;
111: 25257.
Hack M, Schluchter M, Cartar L, Rahman M. Blood pressure among very low birth weight (<15 kg) young adults.
Pediatr Res 2005; 58: 67784. Keijzer-Veen MG, Finken MJJ, Nauta J, Group obotDP-CS.
Risk of Hypertension Among Young Adults Who Were Born Preterm: A Swedish National Study of 636,000 Births. Am.
J. Epidemiol. (2011) 173 (7): 797-803.
Early Hum Dev. 2013 Sep;89(9):743-6. doi: 10.1016/j.earlhumdev.2013.05.008. Epub 2013 Jun 23. The effect of
socioeconomic status on the language outcome of preterm infants at toddler age. Wild KT1, Betancourt LM, Brodsky
NL, Hurt H. Pediatrics.
2014 Mar;133(3):e578-84. doi: 10.1542/peds.2013-0104. Epub 2014 Feb 10. Adult talk in the NICU with preterm
infants and developmental outcomes. Caskey M1, Stephens B, Tucker R, Vohr B.
Hart, B. & Risley, T.R. The Early Catastrophe (2004). Education Review, 77 (1), 100-118.