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of progesterone can reduce the risk of recurrent preterm delivery,4 the prevention of prematurity, which
is an important factor associated with the development of cerebral palsy, has not yet been shown to
be feasible. In the United States, the rates of preterm births (at less than 37 weeks of gestation) and
very preterm births (at less than 32 weeks) have remained virtually unchanged since 1990.5
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The
interventions based
on potential causes
of
medicine
to fetal distress associated with placental vasculopathy no study has yet investigated whether surgical delivery increases or decreases the risk of stroke
in the infant.
In the extensive literature on thromboembolic
disorders in pregnancy, there has been little discussion of the effect of these disorders or of their treatment on the long-term outcome for the infant. Trials of preventive therapies that target fetal or infant
stroke would be challenging, given the relatively low
incidence of the outcome, the difficulty of identifying perinatal stroke in infants who are asymptomatic in the neonatal period, and the absence of
evidence that anticoagulant therapy provided to
pregnant women who are at risk for thromboembolic disease can lessen the risk of stroke in the infant.
intrauterine exposure to infection
Although the frequency of cerebral palsy has not declined, and although there are relatively few specific,
modifiable risk factors for cerebral palsy, attention
to some factors that are associated with an increased
risk of cerebral palsy might help to prevent its development.
perinatal stroke
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A diagnosis of chorioamnionitis (placental infection) during pregnancy is associated with an increased risk of cerebral palsy in infants who weigh
2500 g or more at birth.13,14 In very premature infants, the association of infection with cerebral palsy has been less consistent and, when present, less
strong.14,15 Intrauterine exposure to infections other than toxoplasmosis, rubella, cytomegalovirus,
and herpes simplex virus (the so-called TORCH) infections, has been estimated13 to result in about 12
percent of cases of otherwise unexplained spastic
cerebral palsy in nonmalformed singleton infants
of normal birth weight.
Clinical definitions of chorioamnionitis are imprecise, and for the same specimen, there is often
disagreement between the histologic indicators and
the clinical diagnosis.16 Randomized trials of the
use of antibiotics during pregnancy have been designed to investigate the outcomes of pregnancy or
birth and have not been large enough or followed
children long enough to examine whether such therapy can reduce the risk of cerebral palsy. Because of
the possibility of harmful consequences of the widespread administration of antibiotics during pregnancy,16 an evaluation of the safety and efficacy of
their use in pregnancy would require randomized
clinical trials that included the evaluation of longterm neurologic outcomes.
multiple pregnancy
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evaluated either by auscultation or by electronic fetal monitoring. Electronic fetal monitoring was designed to provide an early warning that permits caregivers to recognize the onset of asphyxial injury to
the fetus. Does its use prevent cerebral palsy?
Randomized, controlled clinical trials of the efficacy of electronic fetal monitoring during labor,
as compared with auscultation, have been systematically reviewed.18 In nine studies of satisfactory
quality, a total of 18,561 women with high-risk or
low-risk pregnancies underwent delivery at seven
clinical centers in the United States, Europe, and
Australia. In the largest of the studies, conducted
in Dublin, Ireland, a nonsignificantly higher rate of
cerebral palsy was observed among children born
to the group of women randomly assigned to the use
of electronic fetal monitoring.20 In a study conducted in the United States,21 there was a significantly
higher rate of cerebral palsy among premature infants whose births had been monitored electronically. Meta-analyses of randomized studies of electronic fetal monitoring during labor18 did not show a
decrease in cerebral palsy with its use or less frequent occurrence of low Apgar scores, admission to
a neonatal intensive care unit, or death. Electronic
monitoring was associated with an increase of 40
percent in cesarean deliveries.
In a casecontrol study that examined the association of abnormalities revealed by electronic fetal
monitoring during labor with the later development
of cerebral palsy,22 even though abnormalities were
more frequent during birth among children who later received a diagnosis of cerebral palsy, three quarters of these children had no such abnormalities.
The false positive rate was 99.8 percent. Among infants with fetal abnormalities on electronic monitoring, the rate of cerebral palsy in those delivered
surgically was not lower than the rate in those delivered vaginally.
When adverse events occur during delivery, they
can be sudden, unpredictable, and catastrophic. Interventions that are aimed at preventing cerebral
palsy as a consequence of adverse events during labor, including interventions based on findings on
electronic fetal monitoring, have not been shown to
be capable of achieving this goal. Reviewing pooled
data from nine industrialized countries, Clark and
Hankins concluded that despite a 5-fold increase
in the rate of cesarean section based, in part, on the
electronically derived diagnosis of fetal distress,
cerebral palsy prevalence has remained stable23
(Fig. 1).
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Cerebral palsy in
developed countries
Cesarean sections
in the United States
10
25
20
15
10
1970
1975
1980
1985
1990
1995
The
2000
Figure 1. The Prevalence of Cerebral Palsy and the Rate of Cesarean Delivery
in Developed Countries.
Pooled data are from Australia, Canada, Denmark, England, Ireland, Norway,
Scotland, Sweden, and the United States. Adapted from Clark and Hankins,23
with the permission of the publisher.
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implications
The known causes of cerebral palsy account for only
a minority of the total cases. Even for most of those
cases, however, evidence of the preventability of the
disorder is lacking.
For future research that may make cerebral palsy
preventable, we need new hypotheses, animal models that will take into account the complexity often
encountered clinically, and careful clinical research.
Trials of preventive interventions will require strategies for term infants that are somewhat different
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