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Marie C. McCormick,1,2 Jonathan S. Litt,2,3
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367
PU32CH20-McCormick ARI 9 March 2011 20:25
weight (ELBW): rity have been seen for both young women and
<1000 g or 2.2 pounds Before ultrasound could determine gestational women 30 years of age and older (9). A portion
Infant mortality: age (GA), most studies of preterm infants relied of the risk among older women is attributed to
number of infant on birth weight designations to characterize risk the use of assisted fertility techniques among
deaths less than 11 e.g., <1500 g [very low birth weight (VLBW) women who have postponed child-bearing.
completed months of 3.3 pounds] and <1000 g [extremely low birth
age divided by the Such techniques are associated with both in-
weight (ELBW), 2.2 pounds]. A recent Insti- creased incidences of multiple births, which are
number of live births
tute of Medicine (IOM) report (3) argues that more likely to be born preterm (3), and higher
the determinant of mortality and much of the rates of preterm delivery in singleton births as
morbidity reects the degree of immaturity of well (3, 9).
fetal development. Weight relative to duration
of gestation may add a component of risk for
adverse neonatal outcomes at the extremes, but INFANT MORTALITY
birth weight is not a proxy for fetal immaturity. AND MORBIDITY
Among preterm births, designations of at
least three levels of risk are becoming accepted: Infant Mortality
infants at the limits of viability (25 weeks); Infant mortality increases sharply with decreas-
very preterm infants (2633 weeks), who will ing GA, from 175.94 per 1,000 live births at
need access to neonatal intensive care for sur- <32 weeks to 2.39 per 1,000 live births at 37
vival; and infants 3436 weeks, now desig- 41 weeks (45). Mortality rates for all premature
nated as late preterm infants (65). Because late infants have declined over the past four decades,
preterm infants generally required less medi- a result of increased survival owing to improve-
cal support to survive, their increased risk for ments in obstetric and neonatal intensive care
complications was underappreciated until re- (3, 14, 51). Of all infant deaths in the United
cent work (65). Because late and moderately States in 2006, 54% occurred among the 2% of
preterm infants are the majority of preterm infants born <32 weeks (45).
births, they constitute a public health concern
less in terms of mortality and more in terms of
morbidity and medical care costs. Neonatal Morbidity
Complications seen in the preterm infant fol-
lowing birth reect both the immaturity of
Trends organ systems and the intensive interventions
For nearly three decades, the rates of prematu- needed for survival. As with mortality, the risk
rity in the United States increased until 2006 of these complications decreases with increas-
(45), with a decline from 12.8% to 12.3% in ing GA and maturation.
Nervous system. Major central nervous sys- associated with improved neurodevelopmental
tem complications include intracranial bleed- outcomes (20, 88).
ing, white matter damage, and sensory impair-
Normal birth weight:
ment (12, 39), affecting 20%25% of VLBW 2500 g or 5.5 pounds
infants. Twenty-ve percent of those with more OUTCOMES
IQ: intelligence
severe hemorrhages will also develop persistent Beyond the newborn period, surviving preterm quotient
hydrocephalus (12). Abnormal development of infants are only at modestly increased (gener-
the immature eye may result in impaired reti- ally 24 times) risk for an array of health, de-
nal function and retinal detachment (retinopa- velopmental, and behavioral problems. Many
thy of prematurity); blindness results in 50% of these problems also occur in term infants.
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of those infants with the most severe and un- Because very preterm infants constitute only a
treated forms (12). The rate of hearing loss relatively small percentage of the overall child
among VLBW or very preterm infants is 2% population, their increased risk for common
Annu. Rev. Public Health 2011.32:367-379. Downloaded from www.annualreviews.org
Growth. Whether poor growth persists into very preterm infants, late preterm infants also
childhood is uncertain. Many investigators have a higher risk of CP, mental retardation,
have shown a relationship of prematurity with developmental disability, blindness, hearing
BPD:
bronchopulmonary low weight, short stature, and smaller head loss, and epilepsy compared with term controls
dysplasia circumference. Others, however, have docu- (64, 66).
mented catch-up growth such that most chil- Additionally, severe visual impairment af-
dren achieve population norms by 611 years fects nearly 10% of children born 26 weeks
of age (6, 19, 29). Being born small for GA de- gestation and up to 2% of those born 32 weeks
creases the chances for catch-up in early child- (56). Up to 6% of children born before 27 weeks
hood (35, 55). may also suffer from profound hearing loss (3).
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conditions, including asthma. A recent meta- Up to 13% of children born <1000 g and
analysis revealed that children born <37 weeks 20% born <750 g have subnormal intelligence
are 7% more likely to be diagnosed with (IQ between 7084). These differences persist
asthma compared with term-born controls; even when neurosensory impairment, neuro-
infants born at lower GA were at highest risk. logic injury, and sociodemographic risk factors
Likelihood of diagnosis lessens over time as are taken into account (27).
children age (33). However, preterm children
also perform poorly on tests of pulmonary School achievement/learning disability.
function when followed into school age (20). Even children without severe neurosensory
Respiratory morbidity results in elevated use impairment or intellectual disability may expe-
of medical care: The majority of extremely rience learning disabilities. Children born with
premature infants experience hospital readmis- low birth weight have higher rates of disability
sions by age two irrespective of the presence of in both reading and math (74, 85), with math
bronchopulmonary dysplasia (BPD) (30). Even reasoning being more severely affected (85).
late preterm infants have increased risk: 15% Very preterm children are more likely to have
are rehospitalized in the rst years of life (42, individual (65%) and multiple (30%) learning
52). In addition, respiratory morbidity, espe- disabilities compared with term controls (13%
cially with prior BPD, is associated with higher and 3%, respectively) (25). Late preterm
medication use, including brochodilators and infants are not immune to neurodevelopmental
inhaled steroids (24, 52), as well as with missed difculties, having been shown to have lower
school days (52), perhaps contributing to school reading scores in kindergarten and rst grade
difculties. (66). Although birth weight and other factors
surrounding birth play a signicant role in
Neurodevelopment (cognitive/motor). special educational placement, it should be
Motor delays in children born preterm are noted that sociodemographic characteristics
common. Rates of cerebral palsy (CP) are of the family also play a role, with greater
6%9% for infants born at 32 weeks and economic or educational advantage playing a
16%28% at 26 weeks gestation (56). In protective role (69).
addition, more subtle neurologic ndings Despite higher rates of learning disabilities,
persist into childhood, leading to problems LBW children with known learning disabilities
with coordination and completion of daily are less likely to have an Individualized Edu-
living activities (3). Fine motor abilities may be cation Plan or receive special education ser-
compromised even without evidence of abnor- vices than are term-born peers (41). The gap
mality on head imaging (77). Although much in achievement between the group of ELBW
of the literature on motor delay is focused on children and normal birth weight controls leads
to differences in grade retention and special ed- Neurodevelopmental outcomes. The rate of
ucation participation (71). CP and other motoric difculties in adolescence
are similar to that seen in younger age groups
Behavior. Compared with term children, (26, 59), with the added feature that the dispar-
preterm children have higher scores on tests of ity in performance compared with term chil-
inattentive and hyperactive behavior, and com- dren appears to be greater for more cognitively
bined forms of attention decit hyperactivity demanding tasks (15). Likewise, IQ differences
disorder, perhaps related to the known prob- noted above persist (1, 15), and even those who
lems with executive function and task comple- have IQs in the average range may have spe-
tion (5, 28). Additionally, ELBW children have cic decits, namely in higher-order executive
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higher scores for measures of autism spectrum function cognitive abilities such as verbal u-
disorders, but only a minority meets full criteria ency, working memory, and cognitive exibil-
for a diagnosis (38). ity. Decits in these skills, needed for academic
Annu. Rev. Public Health 2011.32:367-379. Downloaded from www.annualreviews.org
similar to those born at term (4, 16). Despite (43, 72), and expectations for economic and so-
some studies suggesting an increased incidence cial goals (43) the same as term comparisons.
of asthma (83), respiratory disease is otherwise In fact, many of those without disability have
NICU: neonatal
intensive care unit not a prominent feature of the health of adoles- successfully transitioned to adult employment,
cents and young adults born preterm. education, and family formation (73).
In preterm adolescents and young adults,
higher blood pressures (16, 26) with associated
impaired glucose tolerance (26) and less favor- Factors Influencing Outcomes
able fat distribution (18) have been noted, a GA is not the sole determinant of outcome.
combination that might signal greater risk of Aspects of neonatal intensive care unit (NICU)
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adult onset cardiovascular disease. This risk is admission, including number of complications
of particular concern among preterm infants and duration, confer an increased risk of
born small for GA who experience rapid catch- adverse outcome, especially with respect to
Annu. Rev. Public Health 2011.32:367-379. Downloaded from www.annualreviews.org
up growth in the postnatal period (2, 7). neurodevelopment (26, 36, 38, 39, 62, 78).
Lower birth weights appear to be associated Likewise, an impoverished postdischarge envi-
with lower risks of some cancers (8, 54, 61, ronment might lead to increased cognitive and
92). As with cardiovascular disease, however, behavioral difculties in preterm infants (46).
the effects appear to reect growth for a given
duration of gestation rather than prematurity
per se. Economic Impact
Despite some reports of catch-up growth In a comprehensive review, the IOM estimated
during the preschool period, most very preterm the annual cost of prematurity in the United
adolescents and adults remain smaller and States at more than $26 billion (2005 U.S. dol-
lighter than their term peers (7, 43, 91). Con- lars) (3). This estimate includes medical care
troversy exists about whether very preterm ado- costs of $16.9 billion; the remainder is com-
lescents and young adults have lower bone mass posed of special education, early intervention,
or whether it is appropriate for their smaller size maternal health care costs, and changes in adult
(26, 91). work productivity for both graduates and their
Hospitalization rates in adolescence and families. It is likely an underestimate owing to
young adulthood have been reported to be 16% poor data availability for certain categories of
higher in those born preterm compared with expenses (93).
those born at term. Reasons for hospitalization
were most strongly related to diabetes, eye dis-
orders, epilepsy, and congenital anomalies of PUBLIC HEALTH IMPLICATIONS
the genital organs. Among those born small
Prevention
for GA, the risk of rehospitalization was even
higher, particularly for mental health disorders Few opportunities for prevention are available,
and substance abuse (79). largely because of a limited understanding of
Those born preterm report more disability- the basic biology underlying preterm delivery
limiting work capacity and receipt of disabil- (3). One strategy involves decreasing higher-
ity payments (59). Although they are less likely order multiple births resulting from assisted
to have children of their own, women born reproductive technology. Another might be
preterm are at increased risk of preterm labor improving the accuracy of early pregnancy
(59, 84). GA estimation, thereby reducing the number
Despite preterm adolescents and young of infants inadvertently delivered preterm
adults reporting a greater number and sever- because of inaccurate dates. Both approaches
ity of health problems (43, 71), they rate their will have limited impact on the overall rate of
health-related quality of life (71), self-esteem prematurity. To date, few interventions offered
after the onset of preterm labor have proven chest) (50), most NICUs employ many strate-
effective in preventing preterm birth (3). gies to attempt to normalize the environment
of the infants.
Optimizing the Management of the A variety of postdischarge interventions,
Preterm Infant most of which focus on motor activities and
physical therapy as well as parental skills, have
For those destined to be born preterm, optimal emerged from studies of more general educa-
survival relies on delivery in a setting in which tional programs for disabled or disadvantaged
appropriate medical care is available. Improved children. A recent systematic analysis of this lit-
outcomes, especially for the smallest and most erature (81) concluded that, on average, these
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vulnerable infants, are seen in facilities with the interventions improved cognitive outcome with
capacity, technologic support, and experience little effect on motor development. These re-
for management of preterm infant care (3, 51, sults are driven largely by two major studies:
Annu. Rev. Public Health 2011.32:367-379. Downloaded from www.annualreviews.org
82). Assuring the appropriate level of care is the Avon Premature Infant Project (1a) and
best achieved by characterizing the functional the Infant Health and Development Program
capacity of each hospital within a regionalized (IHDP) (49). Both these studies relied on well-
system of perinatal care, thus assuring access to established curricula and used rigorous designs.
appropriate services (82). Both demonstrated improved cognitive devel-
opment at the end of the intervention period
Quality Improvement and, for IHDP, improved behavior, as well.
An equally important goal is to reduce dif- Although IHDP has demonstrated sustained
ferences in complication rates and outcomes differences favoring the intervention group
among hospitals ostensibly providing the same among moderately premature infants into ado-
level of care (32, 48, 58, 70). Such differences lescence (47), neither intervention led to sus-
can lead to fourfold differential rates of CP tained differences in more immature infants.
and mental retardation among very preterm in- Early intervention has been incorporated
fants (89). Dramatic differences in duration of into the Individuals with Disability Education
hospitalization and technology use have eco- Act (Part C); all states are obliged to offer
nomic implications in the care of moderately some services for children at risk of develop-
preterm infants (48). Quality-improvement ini- mental delay. However, these programs vary
tiatives, including statewide collaboratives with across states in terms of service models, coor-
state health department support, have had vary- dination, and eligibility criteria; participation
ing degrees of success in reducing the variation ranges from 23% to 83% of children identi-
in complication rates (11, 23, 32, 63, 70, 90). ed with a standard denition of eligibility, and
participation is lower for Hispanic and poor
children (53).
Early Intervention
NICU strategies to provide environments more
appropriate to the developmental status of the Establishing Maternal Outcomes
infants evolved to include modications of the The literature on the outcomes of pregnan-
NICU to reduce unnecessary aversive stimuli cies ending prematurely has focused on the
such as excessive light and noise, and to pro- infant and ignores the fact that complicated
mote activities to provide general newborn ex- pregnancies may have consequences for ma-
periences such as rocking or soothing sounds. ternal health. The mothers of VLBW infants
Despite recent documentation of the weakness have been found to have higher rates of de-
of the evidence for any single intervention with pressive symptoms and posttraumatic stress
the exception of massage and possibly skin- disorder, although acute distress may resolve
to-skin care (holding the baby on the parents by six months. The risk of other health
problems is not well established. However, attention than do conditions occurring much
the antecedents of prematurity include chronic more infrequently. The relative failure to pre-
conditions, obesity, and adverse behaviors (3), vent preterm birth over almost two decades ar-
all of which should suggest some postpartum at- gues for a more robust program of basic sci-
tention for the mother and some of which, like ence inquiry to establish the biologic processes
some chronic conditions, may be exacerbated underlying prematurity to identify potential in-
by pregnancy. At least one study has linked tervention strategies. For those infants who are
complications related to prematurity to pre- born prematurely, a growing body of evidence
mature maternal mortality (41a). Thus, an im- suggests that at least some of the morbidity
portant research agenda should be to establish is preventable or modiable. Many of the ap-
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the needs of women who have experienced a proaches to doing so fall squarely in the do-
preterm delivery. main of public health: building and organizing
systems of care, fostering quality improvement,
Annu. Rev. Public Health 2011.32:367-379. Downloaded from www.annualreviews.org
SUMMARY POINTS
1. Premature birth affects more than 12% of all American infants and is a public health
problem.
2. From birth through adolescence, survivors of preterm delivery experience a variety of
health, behavioral, and cognitive difculties, with implications for schooling and their
families.
3. In adolescence, some positive adaptations occur such that those without signicant in-
tellectual disability appear to make a successful transition to adulthood.
4. Potential approaches to prevention seem limited.
5. Reduction of morbidity can be achieved by appropriate management during the newborn
period, reduction of interinstitutional variations in newborn care, and early developmen-
tal intervention.
FUTURE ISSUES
1. There should be a signicant investment in the basic science research on prematurity to
identify effective prevention strategies.
2. More attention should be given to the health of the parents of preterm infants and the
means of providing needed support.
DISCLOSURE STATEMENT
The authors are not aware of any afliations, memberships, funding, or nancial holdings that
might be perceived as affecting the objectivity of this review.
ACKNOWLEDGMENTS
This work was supported in part by grants from the Maternal and Child Health Bureau
(T76MC00001) and Child Health Services Research Training Program (T32 HP10018).
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