Obstetrics & Gynecology:
Chorioamnionitis and the Prognosis for Term Infants
ALEXANDER, JAMES M. MD; MCINTIRE, DONALD M. PhD; LEVENO, KENNETH J. MD
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas.
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: email@example.com
Received June 23, 1998. Received in revised form December 22, 1998. Accepted January 28, 1999.
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.
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 puerperal infection. However, Eschenbach 1 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 infants 3–7 and more recently in term infants. 8 Grether and Nelson 8 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
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 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 χ2 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.
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 (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 postterm 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 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 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 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.
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 and Duff 9 reported that clinical chorioamnionitis complicated 1–5% 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 al 11 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 Nelson 8 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 Nelson 8 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.
1. Eschenbach DA. Amniotic fluid infection and cerebral palsy. Focus on the fetus. JAMA 1997;278:247–8.
2. Centers for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: A public health perspective. MMWR 1996;45:1–24.
3. Morales WJ, Washington SR 3d, Lazar AJ. The effect of chorioamnionitis on perinatal outcome in preterm gestation. J Perinatal 1987;7:105–10.
4. Bejar R, Wozniak P, Allard M, Benirschke K, Baucher Y, Coen R, et al. Antenatal origin of neurologic damage in newborn infants. Am J Obstet Gynecol 1988;159:357–63.
5. Verma U, Tejani N, Klein S, Reale MR, Beneck D, Figueroa R, et al. Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate. Am J Obstet Gynecol 1997;176:275–81.
6. Murphy DJ, Sellers S, Mackenzie IZ, Yudkin PL, Johnson AM. Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies. Lancet 1995;8988:1449–54.
7. Alexander JM, Gilstrap LC, Cox SM, McIntire DM, Leveno KJ. Clinical chorioamnionitis and the prognosis for very low birth weight infants. Obstet Gynecol 1998;91:725–9.
8. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207–11.
9. Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intra-amniotic infection. Am J Obstet Gynecol 1991;164:1317–26.
10. Satin AJ, Maberry M, Leveno KJ, Sherman ML, Kline DM. Chorioamnionitis: A harbinger of dystocia. Obstet Gynecol 1992;79:913–5.
11. Adamson SJ, Alessandri LM, Badawi N, Burton PR, Pemberton PJ, Stanley F. Predictors of neonatal encephalopathy in full term infants. BMJ 1995;311:598–602.
This article has been cited 41 time(s).
Journal of PerinatologyAccuracy of signs of clinical chorioamnionitis in the term parturientJournal of Perinatology
American Journal of Obstetrics and GynecologyThe Maternal-Fetal Medicine Units cesarean registry: Chorioamnionitis at term and its duration-relationship to outcomesAmerican Journal of Obstetrics and Gynecology
Journal of Medical MicrobiologyChorioamnionitis associated with Crohn's disease and azathioprine treatment: a case reportJournal of Medical Microbiology
Clinics in PerinatologyPerinatal infections and cerebral palsyClinics in Perinatology
Paediatrics & Child Health
Management of the infant at increased risk for sepsis
Paediatrics & Child Health, 12():
Journal of Clinical AnesthesiaAnesthetic management of the parturient with fever and infectionJournal of Clinical Anesthesia
American Journal of Obstetrics and GynecologyEvidence for fetal involvement in the pathologic process of clinical chorioamnionitisAmerican Journal of Obstetrics and Gynecology
American Journal of Obstetrics and GynecologyManagement of clinical chorioamnionitis at termAmerican Journal of Obstetrics and Gynecology
American Journal of Clinical PathologySpleen depletion in neonatal sepsis and chorioamnionitisAmerican Journal of Clinical Pathology
American Journal of Obstetrics and GynecologyAcute and chronic chorioamnionitis and the risk of perinatal human immunodeficiency virus-1 transmissionAmerican Journal of Obstetrics and Gynecology
Perinatal Medicine of the New Millennium
Cerebral palsy: Neonatologic responsability
Perinatal Medicine of the New Millennium, ():
Biology of the NeonateChorioamnionitis: A risk factor for fetal and neonatal morbidityBiology of the Neonate
American Journal of Obstetrics and GynecologyInflammation increases vulnerability to hypoxia in newborn piglets: Effect of reoxygenation with 21% and 100% O-2American Journal of Obstetrics and Gynecology
Biology of the Neonate
Chorioamnionitis and fetal/neonatal brain injury
Biology of the Neonate, 79():
American Journal of Obstetrics and Gynecology
Meconium-stained amniotic fluid (MSF) - Reply
American Journal of Obstetrics and Gynecology, 191(6):
Acute thymic involution in fetuses and neonates with chorioamnionitis
Human Pathology, 31(9):
Are complete blood cell counts useful in the evaluation of asymptomatic neonates exposed to suspected chorioamnionitis?
Seminars in Perinatology
Infection and cerebral palsy
Seminars in Perinatology, 24(3):
Seminars in PerinatologyNew developments in the management of preterm laborSeminars in Perinatology
Mental Retardation and Developmental Disabilities Research ReviewsThe epidemiology of cerebral palsy interm infantsMental Retardation and Developmental Disabilities Research Reviews
Journal of Maternal-Fetal & Neonatal MedicineNeonatal outcomes in the setting of preterm premature rupture of membranes complicated by chorioamnionitisJournal of Maternal-Fetal & Neonatal Medicine
Proceedings of the XX European Congress of Perinatal Medicine
Operative or vaginal delivery in suspected intrauterine infection?
Proceedings of the XX European Congress of Perinatal Medicine, ():
Early Human DevelopmentDevelopmental effects on neonatal mortality and subsequent cerebral palsy in infants exposed to intrauterine infectionEarly Human Development
Developmental Medicine and Child Neurology'Defining hypoxic-ischemic birth events'Developmental Medicine and Child Neurology
American Journal of Obstetrics and GynecologyMeconium-stained amniotic fluid is associated with puerperal infectionsAmerican Journal of Obstetrics and Gynecology
Placenta and Neurodisability
The placenta and neurological outcome in the child
Placenta and Neurodisability, 169():
Fetal and Pediatric PathologyRisk factors for maternal intrapartum fever and short-term neonatal outcomeFetal and Pediatric Pathology
American Journal of Obstetrics and Gynecology
Determination of the timing of fetal brain damage from hypoxemia-ischemia
American Journal of Obstetrics and Gynecology, 184(2):
American Journal of Obstetrics and GynecologyIntrapartum fever at term: Serum and histologic markers of inflammationAmerican Journal of Obstetrics and Gynecology
Archives of Disease in Childhood-Fetal and Neonatal EditionEarly postnatal changes in the perfusion index in term newborns with subclinical chorioamnionitisArchives of Disease in Childhood-Fetal and Neonatal Edition
Human PathologyToll-like receptor-2 expression in normal and pathologic human placentaHuman Pathology
2Nd International Congress on New Technologies in Reproductive Medicine, Neonatology and Gynecology
Bacterial infection in the development of fetal and neonatal brain damage
2Nd International Congress on New Technologies in Reproductive Medicine, Neonatology and Gynecology, ():
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie
Chorioamnionitis, not epidural analgesia, is associated with maternal fever during labour
Canadian Journal of Anaesthesia-Journal Canadien D Anesthesie, 48():
European Journal of PediatricsEarly postnatal skin colour changes in term newborns with subclinical histological chorioamnionitisEuropean Journal of Pediatrics
Pediatric PulmonologyDysplasia: A reviewPediatric Pulmonology
Journal of PerinatologyNeonatal early-onset sepsis evaluations among well-apearing infants: projected impact of changes in CDC GBS guidelinesJournal of Perinatology
Seminars in PerinatologyRisk Assessment in Neonatal Early Onset SepsisSeminars in Perinatology
Journal of PerinatologyThe impact of chorioamnionitis on neurodevelopmental outcomes at 3, 8 and 18 years in low-birthweight preterm infantsJournal of Perinatology
Current Opinion in Obstetrics and GynecologyInfection and fetal neurologic injuryCurrent Opinion in Obstetrics and Gynecology
Current Opinion in PediatricsDevelopmental outcome of neonatal intensive care: what questions are we asking?Current Opinion in Pediatrics
EpidemiologyApgar Scores and Long-Term Risk of EpilepsyEpidemiology
© 1999 The American College of Obstetricians and Gynecologists