Transcript Brain Injury in Premature Infants

PREMATURITY:
A Public Health Problem
Charleta Guillory, MD, FAAP
Associate Professor of Pediatrics
Baylor College of Medicine
Associate Director of Level II Nurseries and
Director of Texas Children’s Hospital
Neonatal-Perinatal Public Health Program
Texas Children’s
Hospital is No. 4
among the nation’s
pediatric hospitals
and No. 3 in heart
and neonatology
specialties.
The hospital was
named the No. 1
pediatric hospital in
the South and
Southwest.
INFANT MORTALITY
UNITED STATES, 1915-2001
Rate per 1,000 live births
120
100
80
60
40
20
0
1915
1925
1935
1945
1955
Source: National Center for Health Statistics, final mortality data
Prepared by March of Dimes Perinatal Data Center, 2003
1965
1975
1985
1995
INFANT MORTALITY
The Center for Disease Control’s National
Center on Health Statistics recently
reported that infant mortality increased from
a rate of 6.8 infant deaths per 1,000 live
births in 2001 to a rate of 7.0 per 1,000
births in 2002.
The first year since 1958 that the rate has
not declined or remained unchanged.
Selected Leading Causes of Infant
Mortality
United States, 1990 and 2000
Rate per 100,000 live births
198.1
Birth Defects
141.8
96.5
Preterm/LBW
108.4
1990
130.3
SIDS
2000
62.1
68.5
RDS
24.8
0
50
100
150
200
Source: National Center for Health Statistics, 1990 final mortality data and 2000 linked birth/infant death data
Prepared by March of Dimes Perinatal Data Center, 2002
250
CAUSES OF INFANT MORTALITY:
OKLAHOMA, 2001
INFANT MORTALITY RATES BY
RACE/ETHNICITY:
OKLAHOMA, 1999-2001 AVERAGE
CURRENT DEFINITIONS
• Birth Weight
• Low Birth weight (LBW) - < 2500 grams or 5.5 lbs
• Very low birth weight (VLBW) - < 1500 grams or 3.3
lbs
• Gestation Length
• Premature (preterm delivery, PTD) - < 37 weeks
• Early preterm delivery - < 32 weeks
OVERLAP IN LBW, PRETERM
AND BIRTH DEFECTS U.S. (2002)
Preterm
Births
12.1%
Low
Birthweight
Births
7.8%
Birth Defects
~3-4%
Among LBW: 2/3 are preterm
Among preterm: almost 50%
are LBW (some preterm are
not LBW)
PREMATURITY
• Premature birth is the # 1 killer of newborn
•
•
•
babies
Leading cause of neonatal mortality (0-27 days
of life) in U.S.
Second leading cause of infant mortality in
U.S.
Major determinant of serious health problems:
• Blindness
• Mental retardation
• Lung disease
• neurologic problems
PREMATURITY: AN AMERICAN CRISIS
•
•
480,812 babies/year born preterm in 2002
Approximately 7,000 babies/year born
preterm in Oklahoma (12.7 % of live births)
• 100,000 babies/year end up with lifelong
conditions:
PRETERM BIRTHS
UNITED STATES, 1981, 1991, 2001, 2002
Percent
11.9
12
12.1
10.8
10.1
9.4
7.6
8
4
0
1981
1991
2001
27 Percent Increase
1981-2001
Source: National Center for Health Statistics, final natality data
Prepared by March of Dimes Perinatal Data Center, 2004
2002
2007
2010
March of
Dimes
Objective
Healthy
People
Objective
Preterm Birth Rates by State
United States, 2002
U.S Rate = 12.1%
Percent of Live Births
Note: Value in ( ) = number of states (includes District of Columbia)
Value ranges are based on equal counts
Source: National Center for Health Statistics, 2002 final natality data
Prepared by March of Dimes Perinatal Data Center, December 2003
Over 12.6 (17)
11.4 to 12.6 (16)
Under 11.4 (18)
PRETERM BIRTHS (<37 WEEKS)
BY MATERNAL RACE/ETHNICITY, US, 2001
Percent
18
17.5
13.2
12
11.0
10.3
11.4
11.9
Hispanic
All Races
6
0
White
Black
Native
American
Asian or
Pacific
Islander
Preterm is less than 37 weeks gestation
Hispanics can be of any race
Source: National Center for Health Statistics, 2000 final natality data
Prepared by March of Dimes Perinatal Data Center, 2002
PRETERM BIRTHS:
OKLAHOMA, 1993-2003
PRETERM BIRTHS BY RACE/ETHNICITY:
OKLAHOMA, 2002
RISK FACTORS FOR PRETERM
LABOR/DELIVERY
•
•
The best predictors of having a preterm birth are:
current multifetal pregnancy
a history of preterm labor/delivery or prior low birthweight
mid trimester bleeding (repeat)
some uterine, cervical and placental abnormalities
Other risk factors:
•
•
•
•
•
•
•
•
•
•
multifetal pregnancy
maternal age (<17 and >35 yrs)
black race
low SES
unmarried
previous fetal or neonatal death
uterine abnormalities
incompetent cervix
genetic predisposition
low pre-pregnant weight
•
•
•
•
•
•
•
•
•
•
obesity
infections
bleeding
anemia
major stress
lack of social supports
tobacco use
illicit drug use
alcohol abuse
folic acid deficiency
FACTORS THAT CONTRIBUTE TO
INCREASING RATES OF PRETERM BIRTH
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•
•
•
•
•
Increasing rates of births to women 35+ years of age
Increasing rates of multiple births
Indicated deliveries
• Induction
• Enhanced management of maternal and fetal conditions
• Patient preference/consumerism
Substance abuse
• Tobacco
• Alcohol
• Illicit drugs
Bacterial and viral infections
Increased stress (catastrophic events, DV, racism)
MULTIPLE BIRTH RATIOS BY RACE*
UNITED STATES, 1980-2001
Ratio per 1,000 live births
35
31.1
30.0 30.7
30
27.4
24.4
23.3 23.9
23.0
22.0 22.4
21.0 21.6
20.3
20.3
19.3 19.7 19.9
25
20
32.0
28.6
26.1
25.2 25.7
15
10
5
All Races
White
*Race of child from 1980-1988; Race of mother from 1989-2001
Source: NCHS, final natality data, 1980-2001
Prepared by March of Dimes Perinatal Data Center, 2003
Black
01
20
00
20
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
19
89
19
88
19
87
19
86
19
85
19
84
19
83
19
82
19
81
19
19
80
0
PRETERM BIRTHS
AMONG MULTIPLE DELIVERIES:
OKLAHOMA, 1992-2002
SMOKING AMONG WOMEN OF
CHILDBEARING AGE:
OKLAHOMA, 1999-2003
IMPACT OF SMOKING
•
•
•
•
Smoking during pregnancy is responsible for:
• 20% of all LBW
• 8% of preterm births
• 5% of all perinatal deaths
Pregnant smokers compared to nonsmokers are:
• 2.0-5.0 times as likely to experience PPROM
• 1.2-2.0 times as likely to deliver preterm
• 1.5-10 times as likely to deliver a SGA infant
• 1.5-3.5 times as likely to deliver a LBW infant
Smoking increases risk of stillbirth (RR=1.4-1.6)
• Risk increases with increased amount smoked
Smoking during and after pregnancy increases
risk for SIDS by 3-fold
Prematurity Generates Enormous
Health Care Costs
• Average lifetime medical expenses for a preterm
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•
•
•
baby = $500,000
The total national hospital bill for in patient hospital
stays with any diagnosis of prematurity/low
birthweight was estimated at $13.6 Billion in 2001
Hospital charges for all infants = $29.3 Billion in
2001. Prematurity makes up almost half of all infant
hospital costs
The average hospital charge for a preterm baby is
$75,000 per stay, compared to $1,300 for an
uncomplicated newborn stay.
Maternity & related expenses: Often the largest cost
to employers’ health care plans
* Source: Agency for Healthcare Research and Quality, 2001 Nationwide Inpatient Sample
Prepared by March of Dimes Perinatal Data Center, 2003
What are the adverse short
and long-term outcomes that
these extremely immature
infants are at risk to develop?
INFANT’S BORN AT 22 – 25 WEEKS
Summary of Outcomes Among Infants Born Alive at 22-25 weeks
Outcome
22 Wk 23 Wk 24 Wk 25 Wk
Died in delivery room
84
46
22
16
Survived to Discharge
1
11
26
44
Severe disability @ 30 mo
0.7
5
12
23
Other disability @ 30 mo
0
2
7
10
Survived without overall disability
5
8
15
27
New England Journal of Medicine 2000;343:378-84
ODDS RATIO FOR ADVERSE OUTCOME
Male
2.4
Severe
motor
disability
2.14
Vaginal breech
Systemic steroids
Abnormal HUS
O2 @ 36 wks
2.27
4.74
5.17
2.29
2.48
4.76
6.94
3.17
Variable
Cerebral
palsy
New England Journal of Medicine 2000;343:378-84
OVERALL COGNITION
< 23 wk
24 wk
25 wk
No disability
25%
21%
33%
Mild disability
17%
34%
32%
Moderate disability
33%
18%
19%
Severe disability
25%
27%
17%
New England Journal of Medicine 2005;352:9-19.
NEUROMUSCULAR
< 23 wk
24 wk
25 wk
No disability
75%
70%
79%
Abnormal signs, minimal
functional loss
8%
11%
11%
Cerebral palsy with
disability, ambulatory
12%
8%
6%
Cerebral palsy, nonambulatory
4%
11%
4%
New England Journal of Medicine 2005;352:9-19.
VISION DISABILITY
< 23 wk
24 wk
25 wk
No disability
46%
55%
72%
Squint,
refractive error
Visually impaired,
not blind
Severe blindness
38%
34%
24%
8%
7%
3%
8%
4%
1%
New England Journal of Medicine 2005;352:9-19.
HEARING DISABILITY
< 23 wk
24 wk
25 wk
No disability
88%
85%
93%
Mild hearing loss
8%
7%
2%
Hearing aid, but
hears
Profound hearing
loss
0%
3%
3%
4%
5%
1%
New England Journal of Medicine 2005;352:9-19.
LONG-TERM OUTCOMES
Very Low Birth Weight (VLBW)
infants have poorer cognitive and
behavioral outcomes at school age
compared to normal birth weight
infants.
COGNITIVE AND BEHAVIORAL OUTCOME OF
SCHOOL AGED CHILDREN BORN PRETERM: A
META-ANALYSIS
Bhutta, et al, JAMA, 2002
• Studies from 1980-2001- English language
•
•
•
•
literature
N = 1556 preterm infants vs 1720 term
controls
Infants evaluated after age of 5 years
Term controls had significantly higher
cognitive scores than preterm infants
Preterm born children showed more than
twice the relative risk for developing ADHD.
LONG-TERM OUTCOMES
VLBW infants are associated
with educational disadvantage
that persists into early
adulthood.
Outcomes in Young Adulthood of Very Low
Birth Weight Infants
Hack, et al. NEJM, 2002
• Cohort of 272 VLBW
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infants vs 233 control
infants of normal birth weight
Born 1977-1979 - Assessed at 20 yrs of life
Fewer graduated from high school (74% vs
83%)
Lower mean IQ (87 vs 92) & lower academic
achievement scores
Higher rates subnormal height (10% vs 5%)
More psychopathology among VLBW young
adults than among control subjects
The prevention or amelioration of
disabilities in survivors of extreme
prematurity remains one of the most
important challenges in medicine!
CAVEAT
These results should be interpreted with
the caution since neonatal care and
outcomes for VLBW infants are different
today than 20 years ago.
However, the risk for potential
impairments underscores the need for
anticipatory guidance and early
intervention in this population.
CAN PRETERM LABOR BE
PREVENTED?
•
•
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Primary prevention is the goal
• especially risk reduction in the
preconceptional period and early in
pregnancy
Preterm prevention programs have focused on
risk assessment or prediction of preterm labor
• risk assessment identifies only half of
preterm births
• during pregnancy most biomarkers, even in
combination with risk factors, do not have
good positive predictive values
Causation is the great unknown
WHAT INTERVENTIONS MAY WORK?
“Most interventions designed to prevent preterm
birth . . .are not universally effective and are
applicable to only a small percentage of women
at risk for preterm birth.”
“A more rational approach to intervention will
require a better understanding of the mechanisms
leading to preterm birth.”
Goldenberg RL, et al. Prevention of preterm birth. NEJM 339
(5):313-20, 1998.
POTENTIAL INTERVENTIONS
• Early, comprehensive, accessible, culturally
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sensitive prenatal care
Educate all pregnant women about preterm labor
signs and symptoms and what to do if they occur
Screen and treat all UTIs and STIs
Identify cigarette smokers and intervene (5As)
Assess for alcohol use and intervene
Identify illicit substance users and intervene
Assess for domestic violence and intervene
Eliminate folic acid deficiency
Reduce major stress levels early and throughout
pregnancy
“. . . . . Although we have come a
long way in understanding the
mechanisms involved in the
pathogenesis of prematurity, we
have a long way to go.”
Lockwood CJ. Predicting premature delivery--No
easy task. NEJM, 2002, 346 (4):282-4.
JANUARY 30, 2003
MARCH OF DIMES
PREMATURITY CAMPAIGN
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•
Raise awareness
Reduce rates of
preterm birth
PRETERM BIRTH
LEGISLATION INTRODUCED
“PREEMIE Act”, authorizes
expansion of research into the
causes and prevention of
prematurity and increases
federal support of public and
health professional education as
well as support services related
to prematurity.
MARCH OF DIMES
National Prematurity Campaign