| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Departments of Family Medicine, Environmental and Community Medicine, and Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology and Reproductive Sciences, University of Medicine and Dentistry of New Jersey (UMDNJ)—Robert Wood Johnson Medical School (RWJMS), Piscataway, New Jersey.
Address reprint requests to: Kitaw Demissie, MD, PhD, Department of Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854-5635; E-mail: demisski{at}umdnj.edu
 |
ABSTRACT |
|---|
TOP
 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
METHODS: We carried out a retrospective cohort analysis among singleton live births in the United States for the period 1995–1997 using the National Center for Health Statistics linked birth-infant death cohort data.
RESULTS: Among the 11,246,042 singleton live births during the study period, intrapartum fever (at least 38C) was recorded in 1.6%. Intrapartum fever was associated with early neonatal (adjusted odds ratio [OR], 95% confidence interval [CI] for preterm and term infants respectively: 1.32; 1.11, 1.56 and 1.67; 1.14, 2.46) and infant (OR, 95% CI for preterm and term, respectively: 1.31; 1.14, 1.51 and 1.27; 1.01, 1.59) death among nulliparous mothers. Among preterm infants of parous mothers, intrapartum fever was associated with early neonatal (OR 1.29, 95% CI 1.01, 1.64) death. In the combined analyses (infants of nulliparous and parous mothers), intrapartum fever was a strong predictor of infection-related death. These associations were stronger among term (OR 3.16, 95% CI 1.56, 6.40 for early neonatal; OR 1.75, 95% CI 1.20, 2.57 for infant death) than preterm infants (OR 1.52, 95% CI 1.15, 2.00 for early neonatal; OR 1.29, 95% CI 1.05, 1.57 for infant death). Intrapartum fever was also a risk factor for meconium aspiration syndrome, hyaline membrane disease, neonatal seizures, and assisted ventilation.
CONCLUSION: Intrapartum fever is an important predictor of neonatal morbidity and infection-related mortality.
Maternal fever during labor, defined as a temperature of 38C or more, occurs in up to 7% of term births.1,2 Intrapartum fever is an important criterion for diagnosing clinical chorioamnionitis.3 Although there is incomplete overlap among patients presenting with clinical, histologic, and microbiologic chorioamnionitis, more than 60% of clinical chorioamnionitis cases show evidence of histologic chorioamnionitis.4,5 Although more than 90% of patients with histologic chorioamnionitis demonstrate a positive microbial culture in preterm delivery, this relationship is less than 50% in term deliveries.6 Intrapartum fever is a high-risk marker for neonatal group B streptococcal infection,7,8 and perhaps a risk factor for neonatal encephalopathy and cerebral palsy in term infants.9,10 Maternal temperature elevation during labor can be a nonspecific indicator of maternal and/or fetal infection,11 or can result from increased metabolic rate or poor ventilation.12 A recent study13 found that much of the fever during labor might not be so much a result of infection, but rather a consequence of the use of epidural analgesia. However, some evidence suggests that epidural analgesia is associated with fever during delivery only in the presence of placental inflammation.14 Other characteristics of pregnancy and labor such as prolonged duration of labor and nulliparity have been independently associated with maximum maternal temperature elevation.15
The main purpose of this study was to investigate the effects of maternal fever during labor on neonatal and infant mortality independent of other pregnancy and labor complications. We were particularly interested in examining the association between maternal fever during labor and time of infant death (early neonatal, late neonatal, or postneonatal), as well as causes of death. We hypothesized, a priori, that maternal fever during labor is associated with infection-related death during the first week of life.
|
MATERIALS AND METHODS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
The main outcomes of interest in these analyses were early neonatal (0–6 days), late neonatal (7–27 days), postneonatal (28–364 days), and infant (0–364 days) deaths. For causes of death, we used the classification proposed by International Collaborative Effort on Perinatal and Infant Mortality, which groups the ICD-9 codes for the underlying cause of death recorded on death certificates.17 The grouping includes neonatal and infant deaths due to congenital conditions, immaturity-related conditions, asphyxia-related conditions, infections, and sudden infant death syndrome-related conditions.
The following additional neonatal outcomes noted on the standard birth certificate data were examined: meconium aspiration syndrome, hyaline membrane disease, assisted ventilation, and neonatal seizures during the first 24 hours after birth. The check-box format (yes/no) on the birth certificate allows for the selection of these specific complications and for the designation of more than one complication where appropriate.
Maternal fever during labor, defined as a temperature of 38C or more, was the explanatory (independent) variable of interest. Gestational age information on the birth certificate was derived from the algorithm proposed by the National Center for Health Statistics: (a) computation using dates of child birth and last normal menstrual period; (b) from the clinical estimate; and (c) imputation from last normal menstrual period.18 In more than 95% of pregnancies, gestational age was based on last menstrual period. The clinical estimate of gestation was used if the date of the last menstrual period was not reported and if the period of gestation computed from the date of the last menstrual period was inconsistent with birthweight. For these analyses, preterm birth was defined as a live birth before 37 completed weeks of gestation.
We used the following maternal demographic information to characterize each birth: maternal age in years (under 20, 20–24, 25–29, 30–34, and at least 35), maternal race (white, black, or other), and maternal education in completed years of schooling (under 12, 12, 13–15, 16, and 17 or more). Medical risk factors for the index pregnancy included information on the presence or absence of renal disease, diabetes (includes juvenile onset, adult onset, and gestational diabetes during pregnancy), and hypertensive disorders. Hypertensive disorders included any of the following: (a) chronic hypertension (persistent blood pressure over 140/90 mmHg diagnosed before pregnancy or before 20 weeks’ gestation); (b) pregnancy-induced hypertension (an increase in blood pressure of at least 30 mmHg systolic or 15 mmHg diastolic on two measurements taken 6 hours apart after the 20th week of gestation); or (c) eclampsia (occurrence of convulsion and/or coma unrelated to other cerebral conditions in women with signs and symptoms of preeclampsia). Birth certificate data provided information on number of previous live births and number of spontaneous and induced abortions but not on number of prior stillbirths. For the purpose of this study the number of prior live births was used to define parity. Parity was categorized as nulliparous (no prior live birth) and parous (at least one prior live birth).
Data on characteristics of labor and delivery included delivery method (cesarean delivery, forceps, or vacuum), prolonged labor (abnormally slow progress of labor lasting more than 20 hours), premature rupture of membranes (rupture of the membranes at any time during pregnancy occurring more than 12 hours before the onset of labor), abruptio placentae (premature separation of a normally implanted placenta from the uterus), and placenta previa (implantation of the placenta over or near the internal opening of the cervix).
In addition to descriptive statistics, logistic regression analysis was used to examine the association between intrapartum fever and infant morbidity and mortality (neonatal and postneonatal) before and after accounting for important confounding variables. These relationships were assessed after stratifying the data separately by nulliparous or parous mothers and preterm birth. The confounding variables that were adjusted in the models included maternal age, race, educational status, pregnancy and labor complications such as diabetes, prepregnancy hypertension, pregnancy-induced hypertension, abruptio placentae, placenta previa, premature rupture of membranes, vaginal birth after cesarean delivery, and prolonged labor. Infant’s birth weight and gestational age were also used as confounders in the logistic regression models. Selection and order of entry of confounding variables for the model were based on a priori knowledge about factors that are associated with intrapartum fever and neonatal morbidity and infant death.
|
RESULTS |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
. Mothers who exhibited fever during labor were more likely to be nulliparous and to have diabetes and pregnancy-induced hypertension. The proportion of mothers with prolonged labor and premature rupture of membranes was higher among those with intrapartum fever than those without. Mothers with intrapartum fever were also more likely to be nonwhite and to deliver before 34 weeks. The rates of cesarean and instrumental delivery (forceps or vacuum) were higher among mothers with intrapartum fever.
|
shows neonatal morbidity rates in the presence or absence of intrapartum fever separately for term and preterm infants and for infants born to nulliparous and parous mothers. Intrapartum fever was associated with increased risk for meconium aspiration syndrome, hyaline membrane disease, assisted ventilation, and seizures during the first 24 hours in term infants of nulliparous mothers. However, intrapartum fever was significantly associated with hyaline membrane disease and assisted ventilation in preterm infants of nulliparous mothers. Analyses of the association between intrapartum fever and neonatal morbidity in parous mothers showed similar patterns to those in nulliparous mothers.
|
shows neonatal and infant mortality rates in the presence or absence of intrapartum fever separately for term and preterm infants and for the presence or absence of premature rupture of membranes. Intrapartum fever was associated with an approximately two-fold increased risk for early neonatal, late neonatal, and infant deaths in preterm births with intact membranes. However, mortality rates were not meaningfully different between fever and no fever groups in term infants with intact membranes. Analyses of mothers with premature rupture of membranes showed similar patterns.
|
. Separate logistic regression models were constructed for early neonatal, late neonatal, postneonatal, and infant death after stratifying the analyses according to preterm and term deliveries separately for infants born to nulliparous and parous mothers. Analyses were not stratified by membrane status (with versus without premature rupture) in the logistic models; bivariate analyses failed to reveal an important difference in the association of fever with neonatal or infant mortality between those births with ruptured or intact membranes (Table 3
).
|
Analysis of the association between cause-specific neonatal and infant death with intrapartum fever is shown in Table 5. In both preterm and term infants, intrapartum fever was a strong predictor of infection-related early neonatal and infant deaths. After adjustment for confounders, the odds ratios (OR) for these associations were much higher among term than preterm infants. Stratified analyses by parity did not meaningfully change these associations. In the analyses not stratified by parity, intrapartum fever was not associated with asphyxia-related neonatal and infant death in term and preterm births. When stratified by parity, intrapartum fever was associated with increased risk for asphyxia-related early neonatal (OR 2.81, 95% confidence interval [CI] 1.48, 5.34) and infant (OR 2.42, 95% CI 1.35, 4.35) death in term infants of nulliparous mothers. Intrapartum fever was not associated with asphyxia-related death in preterm infants of either nulliparous or parous mothers. Similarly, there was no association between intrapartum fever and asphyxia-related death in term infants of parous mothers. Stratified analyses by race on the association between intrapartum fever and cause-specific mortality separately in preterm and term infants showed no differences among the races. Among preterm infants, intrapartum fever was associated with immaturity-related early neonatal (OR 1.82, 95% CI 1.51, 2.20) and infant (OR 1.64, 95% CI 1.39, 1.93) death, but not with late neonatal (OR 1.22, 95% CI 0.82, 1.81) and postneonatal (OR 1.34, 95% CI 0.82, 2.18) death.
|
|
DISCUSSION |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Among singletons delivered in the United States in 1995–1997, we found that intrapartum fever was associated with several neonatal morbidities along with neonatal and infant death. Intrapartum fever increased the likelihood of infection-related death in both preterm and term infants. The strengths of our study includes (a) a generalizable population-based cohort; (b) large sample size (about 11.2 million singleton live births); (c) reliable data on mortality during the first year of life as obtained from death certificates; and (d) extensive control for confounding variables. The incidence of intrapartum fever was slightly higher (1.6%) than the previously reported incidence of chorioamnionitis (0.7–1.3%) in which maternal fever was a significant clinical symptom.23,24 This finding most likely can be attributed to additional etiologies of intrapartum fever.
The finding that nulliparous mothers were more likely than parous mothers to exhibit intrapartum fever has been reported by three previous studies.2,15,25 One possible explanation for such a difference could be the higher metabolic expenditures that are associated with contraction of uterine and skeletal muscles in nulliparous as compared with parous mothers.12 Similarly, our findings agree with previous studies that identified premature rupture of membranes, cesarean and instrumental deliveries, and prolonged labor as risk factors for intrapartum fever.2,15,21 Lieberman et al21 did not find an association between premature rupture of membranes and intrapartum fever, but their study was conducted among low-risk pregnancies that were delivered at term. Pregnancy-induced hypertension and diabetes were also identified as additional risk factors for intrapartum fever in the present study. However, the results of studies that examined the association between race, maternal age, and intrapartum fever were conflicting. The distribution of race, maternal age, and educational status between those with and without intrapartum fever did not differ meaningfully in our study, although the difference achieved statistical significance because of large numbers. Although the study of Kevin26 reported a higher proportion of black mothers with intrapartum fever, two other studies1,21 failed to corroborate this finding.27
A recent study1 found a strong association between intrapartum fever and low Apgar score, high frequency of resuscitation, and neonatal seizures during the first 24 hours after birth. The authors of that report emphasized the need for further work to examine the outcomes of pregnancies complicated by intrapartum fever during the first year of life. Our study demonstrates a higher likelihood of presenting with meconium aspiration syndrome, hyaline membrane disease, seizures, and the need for assisted ventilation when labor was complicated by fever. We have also shown that intrapartum fever is strongly associated with infection-related early neonatal and infant deaths among both preterm and term infants and, more surprisingly, with deaths related to asphyxia in term infants of nulliparous mothers. An explanation for the later finding is unclear, although one could hypothesize that the higher metabolic requirements leading to earlier development of acidosis of a fetus in a febrile environment could play a role. Infection-related fevers also may lead to vasculitis/inflammation, which alters vessel tensile strength leading to easier vessel compression and compromise of blood flow.
The finding of a higher magnitude of association between intrapartum fever and infection-related neonatal and infant death among term births may be explained by differences in the degree of aggressiveness in the use of antibiotics in preterm compared with term deliveries. The Centers for Disease Control and Prevention, ACOG, and the American Academy of Pediatrics recognized preterm birth as a high-risk marker for neonatal sepsis, and has recommended the intrapartum administration of antibiotics among all preterm labor patients.7,19,20
The results of our study should be interpreted in light of its limitations. Birth certificate data have been reported to underestimate complications of pregnancy.28 As a result, underreporting of intrapartum fever is likely. This possibility may have resulted in attenuation of associations between intrapartum fever and neonatal and infant outcomes. Thus, the ORs reported in our study are conservative estimates of the true associations. Moreover, the causes of intrapartum fever and the extent of antibiotic use were not captured in the vital statistics data and we were unable to determine the contribution of epidural anesthesia and use of antibiotics to the findings of the present study. Clinical decision for using antibiotics among mothers with intrapartum fever is dependent on factors including gestational age and preterm rupture of membranes. We were able to control for the confounding effects of these factors in the analysis. These factors may serve as a weak proxy for use of antibiotics. However, one can argue that adjustment for premature rupture of membranes may decrease the degree of association between intrapartum fever and adverse outcomes as mothers with premature rupture of membranes represent a subset of patients with chorioamnionitis. Although all mothers with intrapartum fever may not have evidence of infection, our finding that intrapartum fever is not a benign condition underlines the significance of this labor complication regardless of the etiology.
Intrapartum fever is an important determinant of neonatal morbidity and mortality. Strategies to reduce these adverse outcomes through targeted maternal, neonatal, and pediatric interventions will require additional study. Further research is also needed to examine the etiology-specific implications of fever during labor.
|
Footnotes |
|---|
Anna Petrova was a postdoctoral primary care health service research fellow when the research was carried out.
Received September 13, 2000. Received in revised form January 2, 2001. Accepted February 8, 2001.
|
REFERENCES |
|---|
|
TOP
ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
2. Herbst A, Wolner-Hanssen P, Ingemarsson I. Risk factors for fever in labor. Obstet Gynecol 1995;86:790–4.[Abstract]
3. Gibbs RS, Blanco JD, St. Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic fluid from women with clinical intraamniotic infection at term. J Infect Dis 1982; 145:1–8.[Medline]
4. Smulian JC, Shen-Schwartz S, Vintzileos AM, Lake MF, Ananth CV. Clinical chorioamnionitis and histologic placental inflammation. Obstet Gyenecol 1999;94:1000–5.
5. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eshenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988;319:972–7.[Abstract]
6. Zlatnik FJ, Cellhaus TM, Benda JOA, Koontz FP, Burmeister LF. Histologic chorioamnionitis, microbial infection, and prematurity. Obstet Gynecol 1990;76:355–9.
7. Center for Disease Control and Prevention. Prevention of perinatal group B streptococcal disease: A public health perspective. MMWR Morb Mortal Wkly Rep 1996;45: 1–24.[Medline]
8. Towers CV, Suriano K, Asrat T. The capture rate of at-risk term newborns for early-onset group B streptococcal sepsis determined by risk factor approach. Am J Obstet Gynecol 1999;181:1243–9.[Medline]
9. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278: 207–11.[Abstract]
10. Adamson J, Alessandri LM, Badawi N, Burton PR, Remberton PJ, Stanley F. Predictors of neonatal encephalopathy in full term infants. BMJ 1995;311:568–602.
11. Svensson L, Ingemarsson I, Mardh PA. Chorioamnionitis and the isolation of microorganisms from the placenta. Obstet Gynecol 1986;67:403–9.[Medline]
12. Marx GF, Loew DAY. Tympanic temperature during labor and parturition. Br J Anaesth 1975;47:600–2.
13. Lieberman E, Lang JM, Frigoletto F, Richardson DK, Ringer SA, Cohen A. Epidural analgesia, intrapartum fever, and neonatal sepsis evaluation. Pediatrics 1997;99: 415–9.
14. Dashe JS, Rogers BB, Mcintire DD, Leveno KJ. Epidural analgesia and intrapartum fever: Placental findings. Obstet Gynecol 1999;93:341–4.
15. Alexander JM, Mcintire DD, Leveno KJ. Chorioamnionitis and the prognosis for term infants. Obstet Gynecol 1999;94:274–8.
16. National Center for Health Statistics. 1995–97 Linked birth/infant death data set. NCHS CD-ROM Series 20, Numbers 12–14. Hyattsville, Maryland: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 1998–2000.
17. Cole S, Hartford RB, Bergsjo P, McCarthy B. International collaborative effort (ICE) on birthweight, plurality, perinatal, and infant mortality. Acta Obstet Gynecol Scand 1989;68:113–7.[Medline]
18. National Center for Health Statistics. Instruction manual, computer edits for natality data, part 12, 1989. Hyattsville, Maryland: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 1991: 34–6.
19. American College of Obstetricians and Gynecologists. Prevention of early-onset group B Streptococcal disease in newborns. ACOG committee opinion no. 173. Washington DC: American College of Obstetricians and Gynecologists, 1999.
20. Committees on Infectious Diseases and Fetus and Newborn. Revised guidelines for prevention of early-onset group B streptococcal (GBS) infection. Pediatrics 1997;99: 489–5.
21. Lieberman E, Cohen AP, Lang JM, Frigoletto FD, Goetzl L. Maternal intrapartum temperature elevation as a risk factor for cesarean section and assisted vaginal delivery. Am J Public Health 1999;89:506–10.
22. Herbst A, Wolner-Honssen P, Ingemarsson I. Maternal fever in term labour in relation to fetal tachycardia, cord artery acidaemia and neonatal infection. Br J Obstet Gynaecol 1997;104:363–6.[Medline]
23. Huth JC, Gilstrop LC, Haukins GDV, Connor KD. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol 1985;66:59–62.
24. Soper DE, Mayhall CG, Dalton HP. Risk factors for intraamniotic infection: A prospective epidemiologic study. Am J Obstet Gynecol 1989;161:562–70.[Medline]
25. Shurchler D, Menegoz F, Daling J. Reproductive history and intrapartum fever. Gynecol Obstet Invest 1986;21: 182–6.[Medline]
26. Kevin F. Race, perinatal outcome, and amniotic infection. Obstet Gynecol Surv 1996;51:60–6.[Medline]
27. Rickert VI, Wiemann CM, Hankins GD, Mckee JM, Berenson AB. Prevalence and risk of chorioamnionitis among adolescents. Obstet Gynecol 1998;92:254–7.[Abstract]
28. Dobie SA, Baldwin LM, Rosenblatt RA, Fordyce MA, Andrilla CH, Hart LG. How well do birth certificates describe the pregnancies they report? The Washington State experience with low-risk pregnancies. Matern Child Health J 1998;2:145–54.[Medline]
This article has been cited by other articles:
|
|
 |
|
  H. K. Blume, C. M. Loch, and C. I. Li Neonatal Encephalopathy and Socioeconomic Status: Population-Based Case-Control Study Arch Pediatr Adolesc Med, July 1, 2007; 161(7): 663 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 American Heart Association, American Academy of Pe 2005 American Heart Association (AHA) Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) of Pediatric and Neonatal Patients: Neonatal Resuscitation Guidelines Pediatrics, May 1, 2006; 117(5): e1029 - e1038. [Full Text] [PDF]
|
|
|
|
|
|
The International Liaison Committee on Resuscitati The International Liaison Committee on Resuscitation (ILCOR) Consensus on Science With Treatment Recommendations for Pediatric and Neonatal Patients: Neonatal Resuscitation Pediatrics, May 1, 2006; 117(5): e978 - e988. [Full Text] [PDF]
|
|
|
|
 |
|
 Part 13: Neonatal Resuscitation Guidelines Circulation, December 13, 2005; 112(24_suppl): IV-188 - IV-195. [Full Text] [PDF]
|
|
|
|
|
|
Part 7: Neonatal Resuscitation Circulation, November 29, 2005; 112(22_suppl): III-91 - III-99. [Full Text] [PDF]
|
|
|
|
 |
|
 L. Helpman, D. Pauzner, J. B Lessing, M. J Kupferminc, and G. Gutman Chorioamnionitis associated with Crohn's disease and azathioprine treatment: a case report J. Med. Microbiol., August 1, 2005; 54(8): 803 - 804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Getahun, D. Amre, G. G. Rhoads, and K. Demissie Maternal and Obstetric Risk Factors for Sudden Infant Death Syndrome in the United States Obstet. Gynecol., April 1, 2004; 103(4): 646 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Imai-Matsumura, K. Matsumura, A. Terao, and Y. Watanabe Attenuated fever in pregnant rats is associated with blunted syntheses of brain cyclooxygenase-2 and PGE2 Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2002; 283(6): R1346 - R1353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Bartholomew, E. Ashkin, A. Schiffman, and J. W. Larsen Maternal Temperature Variation During Parturition Obstet. Gynecol., October 1, 2002; 100(4): 642 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Jordan, J. L. Jordan, A. Petrova, K. Demissie, and J. C. Smulian Association of Maternal Fever During Labor with Neonatal and Infant Morbidity and Mortality Obstet. Gynecol., December 1, 2001; 98(6): 1152 - 1154. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
