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Is Meconium Passage a Risk Factor for Maternal Infection in Term Pregnancies?

From the Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas; and Information Systems/Decision Sciences Department, University of South Florida, Tampa, Florida.

Address reprint requests to: Allahyar Jazayeri, MD, PhD, Texas Tech University Health Sciences Center, Department of Obstetrics and Gynecology, 3601 4th Street, Lubbock, TX 79430; E-mail: allahyar.jazayeri{at}ttmc.ttuhsc.edu.

	ABSTRACT

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OBJECTIVE: To study the association between meconium and maternal infection.

METHODS: This was a retrospective cohort study of 678 pregnant women. All term deliveries during a 31-month period with meconium passage were included. Each meconium delivery was matched with a consecutive delivery without meconium at the same gestational age.

RESULTS: The overall infection rate was 16%, with 13% of the infections directly related to the pregnancy, labor, and delivery. The endometritis rate was 5%, with 7.1% and 3% in the meconium and no-meconium group, respectively. The chorioamnionitis rate was 8.3%, with 9.5% in the meconium and 7.1% in the no-meconium group. Factors found to be associated with overall obstetric infections had the following odds ratios (ORs) and 95% confidence intervals (CIs): meconium (OR 1.8, 95% CI 1.1, 2.8), internal monitoring (OR 3.4, 95% CI 1.9, 5.9), amnioinfusion (OR 2.0, 95% CI 1.3, 3.3), number of vaginal exams (OR 4.5, 95% CI 2.8, 7.1), length of labor (OR 2.8, 95% CI 1.8, 4.4), and cesarean (OR 3.1, 95% CI 1.9, 5.1). Logistic regression analyses revealed the following ORs and 95% CIs: 1) for endometritis–cesarean (OR 4.2, 95% CI 1.9, 8.9), internal monitoring (OR 2.5, 95% CI 1.1, 5.9), and meconium (OR 2.5, 95% CI 1.1, 5.5), and 2) for chorioamnionitis–length of labor greater than 10 hours (OR 2.7, 95% CI 1.4, 5.6), number of vaginal exams greater than seven (OR 3.4, 95% CI 1.7, 6.6), and use of internal monitors (OR 2.5, 95% CI 1.2, 5.3).

CONCLUSION: Meconium passage increases the risk of post-partum endometritis but not chorioamnionitis. Length of labor, internal monitoring, and number of vaginal exams are risk factors for chorioamnionitis.

Meconium passage occurs in 10–20% of all deliveries and in as many as 40% of post-term pregnancies.¹ Before 37 weeks’ gestation, meconium passage occurs infrequently (5%) and may have a different etiology than term meconium such as intrauterine infection.¹ A strong association between meconium passage in preterm pregnancies and chorioamnionitis has been reported.^2,3 Also, in the presence of meconium, enhanced bacterial growth and inhibition of neutrophil bactericidal activities have been reported.^4,5 Previous studies have shown an association between meconium and maternal infection.^6,7 However, they were either not initially designed to examine meconium and its association with infection,⁶ or had small numbers limiting their ability to analyze other risk factors for infection.⁷

Based on term and preterm reports of infectious morbidity caused by meconium, prospective randomized trials of broad-spectrum antibiotic use in pregnancies complicated by meconium have been performed to reduce the risk of infection.^8,9 These studies have shown that broad spectrum antibiotics given throughout labor intravenously reduced the incidence of maternal infection but did not reduce neonatal infection. When antibiotics were given by amnioinfusion, it did not alter maternal or neonatal outcome significantly.

Because the incidence of meconium passage increases with gestational age,¹ and because preterm meconium may be associated with intramniotic infections, there may be an independent gestational age effect on meconium-associated infectious risk. In a large study investigating meconium as a risk for infection, an increase in gestational age in the meconium group was documented.⁶

Therefore, in studying meconium effects on obstetric infections, one must account for gestational age and preterm-associated intra-amniotic infection risk. To do this, we designed this study with sufficient power to analyze meconium and other risk factors for infection during labor and after delivery in term pregnancies.

	MATERIALS AND METHODS

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The Institutional Review Board at Louisiana State University Medical Center and Texas Tech University Health Sciences Center approved the study. Once a patient delivered at term with meconium, the immediate subsequent delivery without meconium at the same gestational age was selected as the matching control. Patient information, demographics, and clinical data were then extracted from the chart.

Chorioamnionitis was defined as maternal temperature greater than 38C with uterine tenderness and maternal or fetal tachycardia. Endometritis was defined as maternal temperature greater than 38C at least 24 hours after delivery with uterine tenderness without other causes for the fever. The attending physician caring for the patient at the time of hospitalization made the diagnoses of endometritis or chorioamnionitis. The patients with chorioamnionitis were analyzed separately from the patients in the endometritis group because all patients with chorioamnionitis were treated with antibiotics in labor until they were afebrile for at least 48 hours.

Length of labor was determined from onset of regular painful uterine contractions with documented cervical change, or presentation to labor and delivery with cervical dilatation of at least 3 cm, or from initiation of labor induction with oxytocin or amniotomy until delivery. Length of ruptured membranes was defined from the time of spontaneous rupture reported by the patient, which was confirmed by clinical assessment with leakage of fluid, ferning, and test of the alkalinity of the fluid during speculum examination, or from the time of artificial ruptured membrane as part of labor management until delivery.

In the period from July 1, 1998, to February 1, 2001, 678 patients were enrolled (339 with meconium and 339 without meconium), and data were extracted and entered into SPSS 10.0, statistical package for analysis (SPSS Inc., Chicago, IL). Power calculations, assuming a probability of making a type I error of 5% and a type II error of 10% with meconium occurring about 12% of the time and a relative risk of meconium-associated infection of 2.0, revealed that we needed 320 patients in each group. Two-by-two tables were generated and analyzed initially to investigate association, odds ratios (ORs), and statistical significance using ² or Fisher exact tests when appropriate. When multiple associations were found, logistic regression models were built by including covariates identified as potentially important from the two-by-two tables. Model fit characteristics were evaluated using goodness-of-fit tests. The final logistic regression models were designed to address model fit requirements and allow clinical interpretations. To avoid problems with multicollinearity, when significant correlations were found between two independent variables in the model, each one was removed from the model individually, and the model was reanalyzed to evaluate the accuracy of the initial model that included all variables. To account for the one-to-one matching design of this study, dummy variables representing the 339 patient-pairs were included in the logistic regression model and tested for significance. None of these dummy variables were found to be significant in any of the models. In a comparison of the meconium and no-meconium groups, continuous variables were analyzed using paired t tests, whereas categoric variables were analyzed with Wilcoxon signed rank tests and McNemar ² tests. Infection groups were compared using analysis of variance with Dunnett post hoc analysis (continuous variables) and ² analysis (categoric variables). Observed significance levels (P values) less than 5% were considered significant.

	RESULTS

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Table 1 illustrates the demographics of the two groups and indicates that the two groups had similar characteristics except for slightly lower 1-minute Apgar scores in the meconium group. The overall infection rate was 16%. Chorioamnionitis occurred in 8.3% (with 9.5% in the meconium group and 7.1% in the no-meconium group) and endometritis occurred in 5.0% of all deliveries (3.4% of vaginal deliveries and 13.3% of cesarean deliveries). Endometritis occurred in 7.1% of the meconium group and 3% of the no- meconium group (P < .02). Three percent of patients had maternal infection caused by urinary tract infections, upper respiratory tract infections, mastitis, and otitis media. Twenty percent of patients received antibiotics during labor prophylactically or empirically (18% for group B Streptococcus prevention, 2% for urinary tract infections). The distribution of patients who received antibiotics in labor was not different between the meconium group and the no-meconium group (Table 1). All patients undergoing cesarean delivery received antibiotics prophylaxis for the procedure after delivery of the newborn.

	DISCUSSION

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A number of studies have reported an association between meconium and increased maternal infection during labor or after delivery.^2,3,6–8 An association between meconium and term neonatal sepsis^7,8 has never been reported. However, studies of antibiotics used to reduce maternal and/or neonatal morbidity have shown that intravenous broad-spectrum antibiotics given during labor reduced meconium-associated maternal infection rate,⁸ whereas giving the antibiotics through amnioinfusion⁹ did not have an effect on maternal infection rate. Neither study showed a difference in neonatal outcome. The use of antibiotic prophylaxis in a large population of women whose pregnancies have been complicated by meconium passage requires evidence of both benefit to mother and protection to the fetus.

The purpose of our study was to determine the meconium risk for infection by eliminating some of the previous study limitations. To do this, we designed this study with one-to-one matching between controls and meconium pregnancies and included every patient with meconium who delivered during a specific period to reduce the potential for bias. The meconium delivery was matched with the immediate delivery without meconium at the same gestational age. This was done to match gestational age and to standardize selection of matching controls. Individuals who were not aware of the hypothesis being tested collected the data to eliminate risk of selection bias.

Demographic data illustrate the appropriateness of the matching between the meconium deliveries and controls. Previous studies on meconium-associated risk of infection, where patient selection was not based on gestational age and meconium, have shown differences in cesarean rate, number of vaginal exams, rate of internal monitoring, as well as gestational age and birth weight.⁶ All these factors themselves are potential risk factors for infection as illustrated here in our study. Matching the group for gestational age resulted in the two groups having similar demographic characteristics, except for the cesarean delivery rate, which remained slightly higher in the meconium group.

Our results indicated that meconium was not associated with chorioamnionitis in term pregnancies. Length of labor, the use of internal monitoring, and the number of times a woman was examined vaginally during labor were associated with an increased risk of chorioamnionitis. Meconium increased the risk of endometritis by about four times in vaginal deliveries (5.5% versus 1.5%, respectively). Endometritis in these women, who delivered vaginally at term, remained a mild disease, responded quickly to antibiotic therapy, and was not associated with any serious complications such as sepsis, blood transfusion, or loss of a reproductive organ. The maternal hospital stay with or without meconium was not different.

In our study, the diagnosis of infection was based on clinical judgment of the obstetrician caring for the pregnant women and was not confirmed with cultures and/or biopsies. This is one of the limitations of this retrospective study and may result in overdiagnoses of infection. There are differences in our infection rates as compared with others who have examined the same question.^7,8 However, our overall intra-amniotic and postpartum infection rates for vaginal and cesarean deliveries are clearly within accepted rates of infection in the general population,^10,11 and are lower than previously reported infections rates.^6,8 This observation may indicate differences between the populations but argues against overestimation of infectious morbidity in the current study.

The present study was designed to investigate the association between meconium and maternal infection. We found an association between meconium and endometritis in vaginal deliveries only. Meconium may act by different mechanisms to cause endometritis. It may enhance bacterial virulence, through inhibition of the immune response, or may accelerate growth by providing a richer growth media for the bacteria to grow on and invade tissues.^4,5 Alternatively, meconium itself may initiate a foreign body inflammatory response in the uterus and the fallopian tubes, resulting in activation of the inflammatory cytokines, fever, and a clinical picture of endometritis. These potential mechanisms, for the meconium effect, require exposure over a period of incubation. This incubation period may be one reason to explain the meconium-associated risk of endometritis, an infection that can occur hours to days after delivery.

Our results indicate that, in vaginal deliveries at term, meconium passage may increase the risk of endometritis. Given the similar morbidity associated with endometritis between the meconium and no-meconium patients, we speculate that close postpartum observation is safe, will allow early diagnosis for selective treatment of meconium-associated endometritis, and will avoid the unnecessary neonatal exposure to antibiotics.

	Footnotes

 
PII S0029-7844(01)01786-0

Received July 31, 2001. Received in revised form November 15, 2001. Accepted November 29, 2001.

	REFERENCES

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1. Katz VL, Bowes WA. Meconium aspiration syndrome: Reflections on a murky subject. Am J Obstet Gynecol 1992;166:171–3.[Medline]

2. Romero R, Hanaoka S, Mazor M, Athanassiadis AP, Callahan R, Hsu YC, et al. Meconium-stained amniotic fluid: A risk factor for microbial invasion of the amniotic cavity. Am J Obstet Gynecol 1991;164:859–62.[Medline]

3. Mazor M, Furman B, Wiznitzer A, Shoham-Vardi I, Cohen J, Ghezzi F. Maternal and perinatal outcome of patients with preterm labor and meconium-stained amniotic fluid. Obstet Gynecol 1995;86:830–3.[Abstract]

4. Florman AL, Teubner D. Enhancement of bacterial growth in amniotic fluid by meconium. J Pediatr 1969;74: 111–4.[Medline]

5. Clark P, Duff P. Inhibition of neutrophil oxidative burst and phagocytosis by meconium. Am J Obstet Gynecol 1995;173:1301–5.[Medline]

6. Piper JM, Newton ER, Berkus MD, Peairs WA. Meconium: A marker for peripartum infection. Obstet Gynecol 1998;91:741–5.[Abstract]

7. Wen TS, Ericksen NL, Blanco JD, Graham JM, Oshiro BT, Prieto JA. Association of clinical intra-amniotic infection and meconium. Am J Perinatol 1993;10:438–40.[Medline]

8. Adair CD, Ernest JM, Sanchez-Ramos L, Burrus DR, Boles ML, Veille JC. Meconium-stained amniotic fluid-associated infectious morbidity: A randomized double-blind trial of ampicillin-sulbactam prophylaxis. Obstet Gynecol 1996;88:216–9.[Abstract]

9. Edwards RK, Duff P. Prophylactic cefazolin in amnioinfusions administered for meconium-stained amniotic fluid. Infect Dis Obstet Gynecol 1999;7:153–7.[Medline]

10. Sweet RL, Ledger WJ. Puerperal infectious morbidity. A two-year review. Am J Obstet Gynecol 1973;117: 1093–100.[Medline]

11. Gibbs RS, Duff P. Progress in pathogenesis and management of clinical intra-amniotic infection. Am J Obstet Gynecol 1991;164:1317–26.[Medline]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Jazayeri, A. Articles by Sincich, T. Search for Related Content PubMed PubMed Citation Articles by Jazayeri, A. Articles by Sincich, T.