Chorioamnionitis and the Prognosis for Term

Infants
JAMES M. ALEXANDER, MD, DONALD M. MCINTIRE, PhD, AND
KENNETH J. LEVENO, MD
Objective: To assess the effects of clinical chorioamnionitis
and labor complications on short-term neonatal morbidity,
including seizures.
Methods: This was a retrospective cohort study of all
live-born term infants who weighed more than 2500 g
delivered between 1988 and 1997 at Parkland Memorial
Hospital, Dallas, Texas. Infant outcomes were compared
between women with and without clinical diagnoses of
chorioamnionitis. Chorioamnionitis was based on maternal
fever of 38C or greater with supporting clinical evidence
including fetal tachycardia, uterine tenderness, and malodorous infant.
Results: A total of 101,170 term infants were analyzed, 5144
(5%) of whom were born to women with chorioamnionitis.
Apgar scores of 3 or less at 5 minutes, umbilical artery pH of
7.0 or less, delivery-room intubation, sepsis, pneumonia,
seizures in the first 24 hours, and meconium aspiration
syndrome were all increased in infants exposed to chorioamnionitis. After adjustment for confounding factors, including route of delivery and length of labor, chorioamnionitis remained significantly associated with intubation in
the delivery room (odds ratio [OR] 2.0; 95% confidence
interval [CI] 1.5, 2.6), pneumonia (OR 2.2; 95% CI 1.7, 2.8),
and sepsis (OR 2.9; 95% CI 2.1, 4.1). Short-term neurologic
morbidity, manifest as seizures, was not related to maternal
infection during labor, but was significantly related to other
labor complications.
Conclusion: The main short-term neonatal consequence of
chorioamnionitis is infection. Short-term neurologic morbidity in infants is related to labor complications and not
chorioamnionitis per se. (Obstet Gynecol 1999;94:274 8.
1999 by The American College of Obstetricians and
Gynecologists.)

peral infection. However, Eschenbach1 reported that the

hazards of amniotic fluid infections might be greater for
fetuses and newborns. Such infections are now accepted
as a major source of short- and long-term morbidity in
preterm infants. Group B streptococcus prevention programs have been implemented recently in the United
States to reduce such infections in preterm and term
infants.2
Opinions about chorioamnionitis are changing with
reports that cerebral palsy is related to what was
previously considered an exclusively intrapartum maternal infection. Cerebral palsy was linked to chorioamnionitis in several reports on preterm infants37 and
more recently in term infants.8 Grether and Nelson8
found that intrauterine exposure to maternal infection
markedly increased the risk of cerebral palsy in term
infants. Chorioamnionitis was noted as a risk factor for
neonatal outcomes commonly attributed to birth asphyxia.
We sought to determine the immediate effects of
chorioamnionitis on newborn term infants in a cohort of
pregnancies large enough to analyze variables potentially influencing infant outcomes independent of intrauterine infection. We were interested in the relation
between chorioamnionitis and short-term neurologic
morbidity manifest as seizures. We wanted to know
whether chorioamnionitis caused complications in infants or was a marker of other intrapartum events that
led to fetal compromise.

Materials and Methods

Chorioamnionitis, or acute intra-amniotic infection, historically has been associated with maternal morbidity
and mortality. Until recently, the major adverse consequence of chorioamnionitis was considered to be puerFrom the Department of Obstetrics and Gynecology, University of
Texas Southwestern Medical Center, Dallas, Texas.

274 0029-7844/99/$20.00
PII S0029-7844(99)00256-2

Between January 1, 1988 and December 31, 1997, all

live-born infants who weighed at least 2500 g at Parkland Memorial Hospital, Dallas, Texas, were entered in
a computerized database. Delivery events were recorded by attending nurses, and data sheets were
checked for accuracy by research nurses. Infant outcomes were abstracted from the newborn discharge

Obstetrics & Gynecology

records by research nurses, and the results were linked

electronically to the maternal outcomes. This study was
limited to women with singleton pregnancies and live,
cephalic-presenting fetuses at admission to the labor
and delivery unit. Women with diabetes, previous
cesarean deliveries, and fetal malformations were excluded.
Intrauterine infection or chorioamnionitis was diagnosed in women with fever of 38C or greater and
clinical evidence not explained by another source of
infection, including fetal tachycardia, uterine tenderness, or foul odor at delivery. Women with chorioamnionitis received intravenous ampicillin and gentamicin, or clindamycin if they were allergic to penicillin, at
the time of diagnosis. Neonatal sepsis was diagnosed
when blood or cerebrospinal fluid cultures were positive.
We analyzed selected infant outcomes applicable to
term pregnancies in women with and without intrapartum chorioamnionitis. Respiratory distress was diagnosed when infants required mechanical ventilation
beginning in the first 24 hours of life. Seizure activity
apparent during the first 24 hours of life was selected as
an outcome. Meconium aspiration syndrome was diagnosed in infants with clinical and radiographic evidence. All diagnosed infants had dyspnea, tachypnea,
need for supplemental oxygen by 6 hours of life, and
diffuse irregular patchy infiltrates on chest radiographs.
Infants with meconium below the vocal cords but with
no clinical evidence of disease were not diagnosed with
aspiration syndrome.
The strength of associations between classification
variables was measured using the 2 statistic for contingency tables or Fisher exact test when small cell sizes
were expected. Student t test was used to compare the
means of measures between groups. A generalized
estimating equation was used to account for infants
delivered to the same mother (ie, multiparous women).
With this statistic, delivery is grouped by mother such
that within each mother, any variance among deliveries
is adjusted. Any maternal proclivity for specific characteristics (eg, chorioamnionitis, prolonged labor) is accounted for. The measure of association between neonatal outcomes, chorioamnionitis, and other
dichotomous outcomes was adjusted by generalized
estimating equations using the logistic link factor. P
.05 was considered statistically significant. All tests
were two-sided.

Results
A total of 101,170 singleton pregnancies with infants
who weighed at least 2500 g met the inclusion criteria
for analysis. Chorioamnionitis was diagnosed in 5144

VOL. 94, NO. 2, AUGUST 1999

Table 1. Maternal Demographics and Pregnancy

Complications
Chorioamnionitis
Characteristic
Maternal age (y)*
Nulliparous
Race
Hispanic
Black
White
Other
Hypertension
Gestation 42 wk

Yes
(n 5144)

No
(n 96,026)

22.4 5
3856 (75%)

23.3 5
36,876 (38%)

.001
.001

3547 (69%)
985 (19%)
490 (10%)
122 (2%)
728 (14%)
854 (17%)

52,139 (54%)
26,501 (28%)
14,504 (15%)
2881 (3%)
9926 (10%)
10,812 (11%)

.002

.001
.001

* Mean standard deviation.

(5%) of theses pregnancies. Table 1 summarizes selected

maternal demographic and pregnancy characteristics in
women with and without chorioamnionitis. Chorioamnionitis was significantly increased in women who were
younger, nulliparous, or Hispanic. Similarly, chorioamnionitis was significantly associated with intrapartum
hypertension and post-term pregnancies.
Labor characteristics are summarized in Table 2.
Every labor outcome analyzed, including oxytocin stimulation, ruptured membranes without labor, prolonged
labor, fetal heart rate (FHR) decelerations, and cesarean
delivery for dystocia or nonreassuring FHR, was significantly increased in women with chorioamnionitis. As
shown in Figure 1, the incidence of chorioamnionitis
increased in direct proportion to the duration of labor
when measured by admission-to-delivery intervals.
Several complications of infants in the delivery room
and the nursery were significantly increased in mothers
who had chorioamnionitis (Table 3). Larger infants
(birth weight 4000 g or greater) were born more often to
women with chorioamnionitis. For example, 12% of

Table 2. Labor Characteristics

Chorioamnionitis
Characteristic
Oxytocin used
Induction
Augmentation
Ruptured membranes before
onset of labor
Second stage 2 h
Labor time 10 h
Cesarean delivery
Total
Dystocia
Nonreassuring FHR

Yes
(n 5144)

No
(n 96,026)

779 (15%)
2883 (56%)
1245 (24%)

8659 (9%)
18,165 (19%)
8877 (9%)

.001
.001
.001

740 (14%)
3427 (67%)

1635 (2%)
17,887 (19%)

.001
.001

1449 (28%)
1165 (23%)
229 (4%)

6926 (7%)
3716 (4%)
2304 (2%)

.001
.001
.001

FHR fetal heart rate.

Alexander et al

Chorioamnionitis and Term Infants 275

Table 4. Significant Risk Factors Related to

Chorioamnionitis
Risk factor

OR

95% CI

Second stage 2 h
Labor time 10 h
Cesarean for dystocia
Oxytocin used
Cesarean for FHR decelerations
Gestational age 42 wk
Hypertension

9.7
8.6
7.3
6.3
1.9
1.6
1.4

8.8, 10.6
8.0, 9.1
6.8, 7.8
5.9, 6.7
1.7, 2.2
1.5, 1.7
1.3, 1.6

OR odds ratio; CI confidence interval; FHR fetal heart rate.

Figure 1. Frequency of chorioamnionitis in relation to elapsed admission-to-delivery times in 101,170 single term pregnancies (vertical bars
indicate range).

women with chorioamnionitis delivered infants weighing 4000 g or more compared with 8% of women
without it (P .001). Measures of poor infant condition,
including 5-minute Apgar scores of 3 or less, severe
umbilical artery (UA) blood acidemia (pH 7.0 or less),
and need for intubation in the delivery room, were all
significantly increased with chorioamnionitis. As
shown in Table 3, infants born to women with chorioamnionitis had increased rates of respiratory distress,
meconium aspiration, and neurologic abnormalities in
the first 24 hours of life. Culture-proved sepsis and
pneumonia also were increased significantly in women
with chorioamnionitis, although neonatal deaths were
not increased. A total of three neonates born to women
with chorioamnionitis died, two from complications
Table 3. Neonatal Outcomes
Chorioamnionitis
Yes
(n 5144)

No
(n 96,026)

Birth weight (g)*

3465 451
4000 g
616 (12%)
Apgar score 3 at 5 min
27 (0.5%)
Umbilical artery pH 7.0
23 (0.5%)
Intubation in delivery room
84 (1.6%)
Sepsis
69 (1.3%)
Respiratory distress
43 (0.8%)
Pneumonia
98 (1.9%)
Meconium aspiration syndrome
16 (0.3%)
Seizures in first 24 h
14 (0.3%)
Fetal death in labor unit
2 (0.04%)
Neonatal death
3 (0.06%)

3357 439
7673 (8%)
250 (0.3%)
268 (0.3%)
524 (0.6%)
206 (0.2%)
257 (0.3%)
605 (0.6%)
136 (0.1%)
127 (0.1%)
4 (0.00%)
36 (0.04%)

.009
.001
.001
.04
.001
.001
.001
.001
.003
.01
.01
.46

Outcome

* Mean standard deviation.

Positive blood or cerebrospinal fluid culture.

Requiring mechanical ventilation in first 24 hours of life.

276 Alexander et al

Chorioamnionitis and Term Infants

related to sepsis and the third of aspiration followed by

respiratory arrest in the nursery. The cause of aspiration
was not determined, and no autopsy was done.
We ranked the maternal and intrapartum factors
significantly associated with chorioamnionitis according to their odds ratios (ORs) (Table 4). Women with
prolonged labors, as measured by a second stage of 2
hours or longer, labor and delivery times of 10 hours or
longer, need for oxytocin stimulation, and cesarean
delivery for dystocia or FHR decelerations, had the
highest ORs for chorioamnionitis. Chorioamnionitis
and the risk factors shown in Table 4 were used in a
stepwise logistic regression analysis for adverse infant
outcomes (Table 5). After adjustment, chorioamnionitis
remained significantly associated with the need for
intubation of infants in the delivery room, pneumonia,
and newborn sepsis. Seizures, Apgar scores of 3 or less

Table 5. Multivariate Analysis of Maternal and Intrapartum

Factors Related to Neonatal Outcome*
Factor
Intubation in delivery room
Cesarean for dystocia
Chorioamnionitis
Pneumonia
Chorioamnionitis
Newborn sepsis
Delivery time 10 h
Chorioamnionitis
Meconium aspiration syndrome
Cesarean for dystocia
Chorioamnionitis
Seizures
Cesarean for dystocia
Chorioamnionitis
Umbilical artery pH 7.0
Cesarean for dystocia
Chorioamnionitis
5-min Apgar score 4
Oxytocin use
Chorioamnionitis

OR

95% CI

4.1
2.0

3.1, 5.5
1.5, 2.6

2.2

1.7, 2.8

3.4
2.9

2.4, 4.8
2.1, 4.1

3.5
2.2

1.7, 7.1
1.2, 4.0

2.8
1.1

1.5, 5.2
0.57, 2.0

2.4
1.2

1.4, 3.9
0.76, 2.0

2.3
1.3

1.7, 3.05
0.8, 2.0

OR odds ratio; CI confidence interval.

* Most significant association and chorioamnionitis are reported.

Chorioamnionitis was the most significant association.

Obstetrics & Gynecology

at 5 minutes, and UA pH of 7.0 or less were no longer

associated with chorioamnionitis. However, these factors were associated significantly with oxytocin stimulation of labor, prolonged labor times, and cesarean
delivery for dystocia.

Discussion
The results of this analysis of more than 100,000 term
pregnancies suggest that chorioamnionitis in mothers
during labor is associated with adverse infant outcomes. Resuscitation at birth, indicated by intubation in
the delivery room, was required in almost 2% of chorioamnionitis infants. Nearly every measure of compromised infant condition at birth was increased in association with maternal infection during labor. The infants
also experienced morbidity after their arrival in the
nursery, with significant increases in sepsis, pneumonia, meconium aspiration syndrome, and seizures.
The chorioamnionitis story includes more than infant
consequences. Many maternal demographic variables
and labor features were strongly associated with infant
outcomes linked to chorioamnionitis. Nulliparity, race,
intrapartum hypertension, post-term pregnancy, oxytocin stimulation of labor, prolonged labor, and cesarean
delivery were all variables associated with chorioamnionitis and infant risk. Each of the significant labor
features associated with chorioamnionitis was potentially related to maternal demographics. For example,
nulliparous women more often are younger and have
longer labors, and labor is frequently longer in women
who have induction for hypertension or post-term
pregnancy.
We attempted to adjust for the large number of
interacting labor variables linked to adverse infant
outcomes using stepwise logistic regression analysis,
which found that several maternal variables were more
potent modifiers of infant outcome than chorioamnionitis alone. For example, although chorioamnionitis
remained associated with the need for infant resuscitation in the delivery room (OR 2.0; 95% confidence
interval [CI] 1.5, 2.6), cesarean delivery for dystocia was
a more powerful predictor (OR 4.1; 95% CI 3.1, 5.5).
Indices of neonatal infection were most closely related
to maternal chorioamnionitis. For example, chorioamnionitis had strong associations with neonatal pneumonia (OR 2.2; 95% CI 1.7, 2.8) and sepsis (OR 2.9; 95% CI
2.1, 4.1). One interpretation of these results is that
chorioamnionitis in mothers is most closely related to
infections in infants, whereas other labor events determine fetal condition at birth, such as the need for
resuscitation.
The overall incidence of chorioamnionitis in this
cohort analysis is consistent with other reports. Gibbs

VOL. 94, NO. 2, AUGUST 1999

and Duff9 reported that clinical chorioamnionitis complicated 15% of term pregnancies and that this complication was a well-recognized risk after ruptured
membranes and prolonged labor at term. We found a
direct correlation between the duration of labor and
clinical infection in mothers. Such a link between infections and duration of labor implicates dysfunctional
labor, need for oxytocin stimulation, and cesarean delivery as covariables in adverse infant outcomes associated with maternal chorioamnionitis. Under these circumstances, chorioamnionitis is a marker of abnormal
labor.10 This observation does not minimize the deleterious effects on infants of maternal chorioamnionitis in
labor, but emphasizes that the primary neonatal consequence of abnormal labor is infection in newborns.
Other investigators have concluded recently that maternal infection during labor at term has short- and
long-term consequences for infants, but that there are
many interacting, confounding variables implicated in
infant outcomes. Adamson et al11 analyzed 89 full-term
infants who suffered neonatal seizures and found that
maternal infection in labor was just one of 15 antepartum or intrapartum factors associated with brain injury
in infants. Grether and Nelson8 reported that intrauterine exposure to maternal infection was associated with
a marked increase in cerebral palsy in infants delivered
at term. Similar to our results, their newborns exposed
to chorioamnionitis were more often depressed at birth
and suffered seizures. Grether and Nelson8 concur with
our finding that the link between maternal infection and
cerebral palsy is confounded by several maternal characteristics besides intrapartum infection. They computed adjusted ORs for factors individually found to
influence the link between maternal infection and cerebral palsy. In their analysis, none of the many factors
remained significant for cerebral palsy after regression
analysis; however, they did not adjust for duration of
labor, which we found to be the most powerful predictor of immediate newborn morbidity attributed to chorioamnionitis. Our results, unlike those of Grether and
Nelson,8 suggest that short-term abnormal neurologic
outcomes (seizures in the first 24 hours of life) are not
causally related to maternal infections, but to abnormal
labors.

References
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on the fetus. JAMA 1997;278:247 8.
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MMWR 1996;45:124.
3. Morales WJ, Washington SR 3d, Lazar AJ. The effect of chorioamnionitis on perinatal outcome in preterm gestation. J Perinatal
1987;7:10510.

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Chorioamnionitis and Term Infants 277

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KJ. Clinical chorioamnionitis and the prognosis for very low birth
weight infants. Obstet Gynecol 1998;91:7259.
8. Grether JK, Nelson KB. Maternal infection and cerebral palsy in
infants of normal birth weight. JAMA 1997;278:20711.
9. Gibbs RS, Duff P. Progress in pathogenesis and management of
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10. Satin AJ, Maberry M, Leveno KJ, Sherman ML, Kline DM. Chorioamnionitis: A harbinger of dystocia. Obstet Gynecol 1992;79:9135.
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Address reprint requests to:

James M. Alexander, MD
Department of Obstetrics and Gynecology
University of Texas Southwestern Medical Center at Dallas
5323 Harry Hines Boulevard
Dallas, TX 75235-9032
E-mail: jalexa@mednet.swmed.edu

Received June 23, 1998.

Received in revised form December 22, 1998.
Accepted January 28, 1999.

Copyright 1999 by The American College of Obstetricians and

Gynecologists. Published by Elsevier Science Inc.

Obstetrics & Gynecology