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Longterm Outcomes_10.16.13
1. Preterm Birth, So What?
Long term health
outcomes of prematurity
Courtney Gravett, MPH
Courtney.gravett@seattlechildrens.org
CORE Group Fall 2013
2. Magnitude of the problem
•15 million babies born preterm every year
•2nd leading cause of under-5 mortality:
• Preterm birth and stillbirth take more newborn lives
than HIV, TB and malaria combined.
•Preterm birth is the most frequent cause of infant
mortality and morbidity in United States
3. What is Preterm?
Classification by gestational age:
• Late Preterm: 34-36 weeks
• Moderately Preterm: 32-33 weeks
• Very Preterm: 28-31 weeks
• Extremely Preterm < 28 weeks
Classification by birth weight:
• Low birth weight (LBW) < 2500 g
• Very low birth weight (VLBW) < 1500 g
• Extremely low birth weight (ELBW) < 1000
4. Overlap in LBW and Preterm Births
Among LBW:
2/3 are preterm
LBW
7.9%
Among preterm:
more than 43% are
LBW (some preterm
are not LBW))
Source: National Center for Health Statistics, 2003 file. Prepared by the March of Dimes Perinatal
Data Center, 2006.
5. Why it matters
•Increased survival of preterms and the rise in associated long
term health consequences represent a significant public health
concern
•The long-term medical, educational, and productivity costs
borne by the individual, as well as by the family and society, are
significant but not well understood.
•Recent research indicates that PTB has multiple, systemic,
longstanding effects on development and disease risk later in
life
6. PTB and disease risk throughout the lifetime
Respiratory distress syndrome,
necrotizing entercolitis, intraventricular
hemmorhage, retinopathy of prematurity
sepsis, mortality, feeding problems
~10% of births
Mothers at risk
for depression,
anxiety, future
Cerebral
preterm labor palsy, developmental
delay, higher morbidity &
mortality, behavior and learning
problems, asthma
Diabetes/insulin
resistance,
hypertension,
reduced fertility
Source: Iams JD, Creasy RK. Preterm labor and delivery, Chapter 34.
In: Maternal-Fetal Medicine: Principles and Practice, 5th ed., 2004.
7. Risk is directly related to degree of
immaturity & modified by other factors
28 wk
32 wk
36 wk
40 wk
Risk
Prenatal
exposures
Extrauterine
exposures
Home
Environment
8. Brain growth in the last trimester
• The brain is the last
major organ to
develop
• The baby’s brain at
35 wks weighs only
2/3 what it will
weigh at term
• Lots of important
brain growth
happens in those
last few weeks
Image from March of Dimes
9. Preterm Brain Injury: Long Term Effects
• Motor
• Cognitive
– Hypotonia (initially)
– Hypertonia
• Cerebral palsy
– Spastic diplegia
– Delays
• Gross
• Fine
– Delays
– Mental retardation
• Speech/Language
– Delays
• Expressive
• Receptive
Wood N, et al. Neurologic and developmental disability after extremely preterm birth: The EPICure study
group. N Eng J Med. 2000; 343(6):378.
Baron I, et al. Late preterm birth: A review of medical and neuropsychological childhood outcomes.
Neuropsych Rev. 2012; 22:438.
10. Prematurity and Developmental Disability
Prevalence per 1000 children by Gestational Age
20-23 wk
24-28 wk
29-32 wk
33-36 wk
>37 wk
Cerebral Palsy
49.9
49.9
16.7
3.2
1.3
Mental
Retardation
76.0
60.9
27.2
12.9
6.8
Hearing Loss
14.3
6.3
1.9
1.0
0.7
Vision
Impairment
11.9
16.1
2.9
1.0
0.5
Developmental disabilities by gestational age among
survivors to age 3
Preterm Birth: Causes, Consequences, and Prevention. IOM; Behram RE, Butler AS, editors. Wahington DC:
National Academies Press: 2007.
11. Significant delays seen even in moderate to
late preemies
Increased long-term developmental delays and decreased IQ
for babies born at even 35 - 37 weeks compared to 39 weeks
Kerstjens J, et al. Developmental delay in moderately preterm born children at
school entry. J Pediatr. 2011; 159:92.
12. Behavioral and emotional problems
Child Behavior Problems
Odds ratio
Total problems
1.84*
Externalizing problems
1.69*
Internalizing problems
2.40*
Emotionally reactive
1.70
Anxious/depressed
2.50
Somatic complaints
1.92*
Withdrawn
1.38
Sleep problems
1.88
Attention problems
1.80
Aggressive behavior
2.03
Risk for clinical problem scores in moderately preterm vs term
children at preschool age
*indicate significance
Potijk M, et al. Higher rated of behavioral and emotional problems at preschool age in children born
moderately preterm. Arch Dis Child. 2012:97:112.
14. Preterm birth and Cardiovascular Health
• Preterm birth is an emerging risk factor for
– Hypertension (2.5 to 3.8mmHg higher than term)
de
Jong 2012
– Diabetes (Hazard ration 1.67) Kaijser 2009
– Cardiovascular disease Crump 2011
– Stroke Koupil 2005
• Cardiovascular structure and function are
significantly altered after preterm birth
– In young adults born preterm, the left ventricular mass
is increase and left ventricle smaller
– In teenagers born preterm the aortic cross sectional
area is 20% smaller
Norman M. Premature birth: Implications for cardiovascular health. Future Cardiol. 2013;9:293.
15. Example: Altered cardiac structure
and function into young adulthood
• Compared to term infants, preterm infants have
– significantly increased left ventricular mass (66.5 g/m2
compared to 55.55 g/m2, p<0.001)
– Reduced systolic and diastolic function
• This effect was further modified the underlying
etiology or prematurity
– Maternal preeeclampsia was associated with further
reduction in left ventricular strain
• This is a clinically meaningful difference that may
modify future risk for heart disease
Lewandowski AJ, et al. Preterm heart in adult life: Cardiovascular magnetic resonance reveals distinct
differences in left ventricular mass, geometry and function. Circulation. 2013; 127:197-206
16. Preterm birth and asthma
• Late preterm birth (34-36 weeks) and low-normal
(37-38 weeks) was associated with increased risk
of:
– Asthma (OR 1.68 LPT) (OR 1.34 low-normal)
– Inhaled corticosteroid use (1.66) (1.39 ) low-normal
– Number of acute respiratory visits (1.44 LPT)
• Late-preterm and low-normal gestational ages
may be a risk factor for asthma
• Preterm lungs subject to insult
from medical intervention
Goyal NK, Fiks AG, Lorch SA. Association of late-preterm birth with asthma in young children: practicebased study. 2011. Pediatrics; 128(4)
17. Impact on mother and family
• Mothers of preemies experience more
psychological distress than those of term babies
– Increased incidence of post-traumatic stress symptoms
– At 18 months only 30% of preterm moms had secure
attachment to babies, compared to 60% of term moms
• Parents of preemies may continue to see children
as vulnerable, even when child is no longer
medically fragile
• Increased economic burden on family
Latva R, et al. How is maternal recollection of birth experience related to behaviorial and emotional
outcome of preterm infants? Ear Hum Develop. 2008;84:587.
Shaw R, et al. Prevention of posttraumatic stress in mothers with preterm infants. Issues in Mental
Health Nursing. 2013;34:578.
18. Variables that affect the premature
infant’s developmental trajectory
Gestational age
Birth weight
Nutrition
Smoking
Socioeconomic
status
Medical
interventions
Mechanical
ventilation
Infection
Brain injury
Postnatal
growth
Health Outcome
19. Public Health Implications
• Increased burden on health care system
• Increased costs to society
–
–
–
–
Healthcare costs
Educational costs
Social service costs
Loss of productivity
• Must increase awareness of providers that individuals
born preterm are at increased risk of chronic disease
• Better linkages between providers and social services
• When possible, it is important to maintain pregnancy to
full term
Petrou S et al. Child Care Health Dev. 2001;27:97-115
Petrou S et al. Early Hum Dev. 2006;82:77-84.
20. Future Directions
• Identify and promote protective factors for child development
– e.g. close bond with a caregiver
• Provider and family member education to mitigate other risk
factors
– e.g. discourage smoking, encourage proper nutrition
• Take a coordinated approach to postpartum and neonatal
care
• Early detection and intervention for children with signs of
delay or disability- linkage to services
• Increase availability and access to known interventions
across the MNCH spectrum
Every year, millions of women risk their lives giving birth; nearly half of all maternal deaths and one-third of stillbirths occur during childbirth. Improving maternal and child health is essential for the sustainable health of families and communities.
In developed nations, most low-birthweight infants are preterm. In under-developed nations, the proportion of term low-birthweight infants is higher due to the greater prevalence of malnutrition.
The relative influences
of gestational age and fetal growth
are difficult to disentangle completely
because of correlation
In the U.S., two-thirds of low-birthweight infants are preterm (<37 weeks), and half of preterm infants weigh less than 2,500 grams. This is explained on the next slide.
Advances in neonatal intensive care means that more infants are surviving with disabilities and adverse developmental outcomes
A real concern, especially for resource constrained settings
Shifting from a pregnancy comlication to a developmental complication
Accounts for 1/3 of infant deaths in USA, 45% cerebral palsy, 35% vision impairment, and 25% cognitive or hearing impairment, 75% of perinatal mortality
Risk of complications increases with increasing immaturity
The likelihood of perinatal death decreases substantially as the gestational age at birth increases, especially between 24 and 28 weeks of gestation. The data in this slide comes from a population-based cohort of 8,523 infants born in 1997-98 in Memphis (Mercer BM, 2003) and is typical of national data.
Preterm infants born before 32 weeks have a substantially increased risk of long-term disability and death: 19 percent of infants born before 32 weeks die within the first year of life, compared with 1 percent of infants born at 32–36 weeks, and 0.2 percent of infants delivered at 37–41 weeks (Mathews TJ, MacDorman MF, 2006).
Dose response effect of prematurity
Majority of PTB are moderate to late preterm
Organ maturation is still occuring in this critical time period
Difficult to parse out the effect of prematurity per se
The brain of a preterm infant at 35 weeks weighs only 2/3 of what it will weigh at full term. That means a lot of important things are happening in the brain in those last few weeks. These include growth and alignment of the brain cells, and creating billions of connections that form the functional units that will process messages in the brain. If the baby is born early, the brain continues to grow and develop, but may not develop normally.
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 30-32 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
1/3 of late preterms displayed school problems including ADD and hyperactivity (19%), poor performance in fine motor skills and writing (32%)
Preterm & LBW infants have higher systolic blood pressure later in life
Left ventricle- equals the effect assocaited with a 9kg/m2 BMI increase
Aortic- an effect that exceeds that of smoking during pregnancy
The effect of prematurity on LV mass equaled the effect that can be associated with a 9 to 10 point higher BMI
Retrospective cohort study of children born between 34 and 42 weeks monitored from birth to 18 months
Affects parent child interactions- May increase difficulities in maternal bonding
Mothers of preemies report more negative experience of birth even six years later and negative experience of first contact with infant
Feeling that baby did not belong to them. Mothers with brief contact had better bonding with newborn
Mothers who display PTSD symptoms tend to view their children as more difficult and less easily soothed
Parents of preemies may continue to view child as vulnerable resulting in rigid, overprotective parenting styles
Health-care costs
e.g., monetary value related to use of community health services
Educational costs
e.g., additional assistance (such as special education) required as a result of school failure & learning problems
Social service costs
e.g., utilization of developmental services such as day care programs, case management & counselling, or respite care & residential care
Out-of-pocket expenses
e.g., additional travel costs related to going to health & social care providers or accommodation expenses
This slide identifies the various sources for additional long-term care costs associated with premature and low-birthweight (LBW) infants. Economic studies examining the long-term care costs of premature infants are limited. In a 2001 review article by Petrou et al., the authors examined the existing literature and provided some long-term care cost estimates associated with premature and low-birthweight infants. The authors categorized costs and economic consequences related to health care, education, social services and out-of-pocket expenses following the infants’ initial discharge from the neonatal unit. While they acknowledge the differing methodologies used in studies, the review showed higher long-term care costs for preterm or LBW compared to term infants. The authors also note that some studies were based on British cohorts and may not be generalizable to infants born in the U.S. health-care system. A more recent study in England compared the “mean societal costs” of 241 preterm children (20-25 weeks of gestation) against 160 term children during their sixth year after birth. The authors linked unit costs associated with use of health, social and other services or resources for each child during a 12-month period and found a statistically significant higher mean cost difference of $10,600 (converted to U.S. dollars) per preterm child. Again, one of the authors’ conclusions was that extreme preterm birth was “a strong predictor of high societal costs” (Petrou S et al., 2006).
Sources: Petrou S, Sach T, Davidson L. The long-term costs of preterm birth and low birth weight: results of a systematic review. Child Care Health Dev. 2001;27:97-115; Petrou S, Henderson J, Bracewell M et al. Pushing the boundaries of viability: the economic impact of extreme preterm birth. Early Hum Dev. 2006;82:77-84.
