| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
ORIGINAL RESEARCH |
From the Departments of Obstetrics and Gynecology, Pathology, Center for Statistical Sciences, and Pediatrics, Brown University, Women and Infants’ Hospital, Providence, Rhode Island.
 |
Abstract |
|---|
Top
 Abstract Materials and MethodsResultsDiscussionReferences |
|---|
Methods: We conducted a cohort study of 287 VLBW infants delivered as a result of preterm premature rupture of membranes (PROM) or preterm labor. Control subjects (n = 123) had placentas with absent umbilical cord inflammation and absent or low-grade membrane inflammation. Case subjects (n = 164) had moderate membrane inflammation or any umbilical cord inflammation. Neonatal and 7-month outcomes were compared. A power analysis showed that 98 total subjects were needed to reject the two-sided null hypothesis with a difference in mean Bayley index scores of at least 8.
Results: Infants in the study group had significantly more preterm PROM, antenatal antibiotics, lower birth weight, lower gestational age, longer duration of ruptured membranes, and clinical chorioamnionitis. Intraventricular hemorrhage occurred more commonly in infants with placentas demonstrating chorioamnionitis (relative risk = 1.6, 95% confidence interval 1.1, 2.4, P = .013). One hundred sixty-seven (69%) of the 243 surviving infants had 7-month follow-up. There was no difference between cases and controls in mean Bayley mental developmental index (93 compared with 90, P = .25), psychomotor developmental index (89 compared with 90, P = .68), or in the number of infants that were developmentally delayed.
Conclusion: Despite a higher frequency of intraventricular hemorrhage, no difference in developmental scores was detected at 7 months of corrected age in VLBW infants with histologic chorioamnionitis.
Although neonatal care continues to improve, infants delivered at gestational ages near the limits of viability have high rates of mortality and morbidity. Intrauterine infection is commonly identified in pregnancies delivered prematurely. Higher frequencies of histologic chorioamnionitis in preterm placentas compared with those at term have been well documented.1–4
Several studies have reported an adverse effect of clinical and histopathologic chorioamnionitis on neonatal outcome. Hardt et al5 found a decreased Bayley mental developmental index score at 1 year of age in infants exposed to chorioamnionitis, whereas Morales6 did not. Russell7 reported higher rates of perinatal death and neonatal sepsis in the first 48 hours of life in infants whose deliveries were complicated by histopathologic chorioamnionitis. Similarly, Zhang et al8 reported that neonatal morbidity (sepsis, respiratory distress, fever) was higher in infants delivered with placentas demonstrating chorioamnionitis or funisitis.
Because chorioamnionitis often complicates preterm birth and can affect neonatal outcome, we studied the outcome at 7 months of corrected age in neonates with placentas demonstrating histologic chorioamnionitis. Very low birth weight (VLBW) infants would be expected to be particularly susceptible to the potential consequences of infection. Our null hypothesis was that there would be no difference in mean Bayley developmental index scores at 7 months of corrected age in VLBW infants exposed to placental chorioamnionitis compared with infants not exposed.
|
Materials and Methods |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Infants born of multiple gestations for whom birth order was not indicated on the placental specimen were excluded, because the placenta corresponding to the neonate enrolled in the study could not be determined. Placental specimens included a minimum of two segments of umbilical cord, one parenchyma section including chorion and amnion, and a membrane roll extending from the area of rupture to the margin of the placenta. Specimens without this minimum of sections were excluded. Tissue sections were stained with hematoxylin and eosin.
The definition of histopathologic chorioamnionitis was determined at the outset of the study and was adopted from that used clinically at Women and Infants’ Hospital. The umbilical cord was given a grade of 0 if it contained no polymorphonuclear leukocytes (PMNs) through grade 3 for funisitis if PMNs were present in the Wharton jelly regardless of the presence of vasculitis. A blood vessel was considered positive for vasculiltis if the vessel wall contained PMNs. If the umbilical cord was without funisitis but contained one vessel with vasculitis it was designated as grade 1. The presence of two- or three-vessel vasculitis without funisitis constituted grade 2 inflammation. The amnion and chorion of the membrane roll and of the parenchyma section were each graded according to the leukocyte density in the area of highest PMN concentration as follows. Specimens with no PMNs were grade 0, and those with one to ten PMNs per high-power field were grade 1. Grade 2 specimens had 11 to 50 PMNs in a high-power field. Amnion or chorion with higher concentrations of PMNs were designated as grade 3. The higher grade of inflammation of the amnion/ chorion in the membrane roll and in the parenchyma section was designated as the grade of membrane inflammation. A placenta was considered negative for chorioamnionitis if the umbilical cord inflammation was grade 0 and membrane inflammation was grade 0 or 1. Subjects with those grades constituted the control group. All specimens with grade 2–3 inflammation of the membranes or grade 1–3 inflammation in the umbilical cord were considered positive for chorioamnionitis and comprised the study group. A single examiner (HP) reviewed all slides without knowledge of the clinical outcomes.
Clinical chorioamnionitis was defined by criteria introduced by Gibbs et al.14 These criteria required a maternal temperature of 100F or higher and two of the following: maternal heart rate above 120 beats per minute, fetal heart rate above 160 beats per minute, foul smelling amniotic fluid, fundal tenderness, and maternal white blood cell count above 14,000/mL, in the absence of another source of infection. Infants delivered of mothers who did not meet these criteria were considered negative for clinical chorioamnionitis.
Maternal treatment decisions were at the discretion of the attending obstetrician. In women with preterm PROM, tocolytics and digital vaginal examinations were routinely avoided. Mothers with preterm labor were typically offered tocolytic therapy. Prophylactic antibiotic use and corticosteroid use varied, and their frequency of use was noted. Surveillance for clinical chorioamnionitis included serial fetal heart rate tracings, leukocyte counts, daily maternal vital signs, and examinations for fundal tenderness. Cesarean delivery was done for standard obstetric indications.
One author (SD) reviewed all maternal charts and extracted data from all cases of preterm PROM and preterm labor. These data included presence or absence of clinical chorioamnionitis, duration of ruptured membranes, and route of delivery. Mothers were considered to have had preterm PROM if spontaneous rupture of membranes occurred before the onset of labor. Rupture of the membranes was diagnosed in most cases by the presence of vaginal pooling, ferning, and basic pH on sterile speculum examination. Mothers were considered to have had preterm labor if delivery occurred after idiopathic preterm labor in the absence of preterm PROM. A second reviewer (MM) examined maternal charts if information was questionable on initial review, and a consensus was reached.
Statistical analyses were done initially using the two-tailed Student t test for means comparison for the normally distributed Bayley developmental index scores and the Mann-Whitney U test for other continuous variables. The two-sided Fisher exact test was used for categoric data. Multiple regression analyses were used to assess the association between chorioamnionitis status and Bayley developmental index scores, adjusting for gender, birth weight, gestational age, intraventricular hemorrhage, multiple gestation, preterm labor or preterm PROM, antibiotic use, and duration of ruptured membranes. Additionally, developmental index scores were dichotomized to determine the frequency of both suspected (score less than 85) and diagnosed (score less than 70) developmental delay. Logistic regression analyses were used to assess differences between cases and controls, adjusting for the aforementioned factors. Outlier and influence analyses were conducted for regression models using standard procedures. The statistical models fit the data remarkably well. Analyses were repeated after regrouping control subjects with grade 1 membrane inflammation and grade 0 umbilical cord inflammation into the case group. A separate analysis was also performed excluding control subjects with clinical chorioamnionitis. A sample size calculation indicated that 49 subjects would be needed in each group given a type 1 error of 5% and a power of 80% to identify a difference in mean Bayley scores of at least 8, which represents one half of a standard deviation and was also believed to be a clinically significant difference. The 100 cases and 67 control subjects available for analysis exceeded the sample size calculation. The study was approved by the institutional review board. A P value of less than .05 was considered significant.
|
Results |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
. There were 519 liveborn deliveries of VLBW infants at Women and Infants’ Hospital between January 1, 1990 and December 31, 1994. Fifteen maternal charts (2%) were not available, resulting in 504 charts reviewed. Of the 504 charts reviewed, 358 (71%) infants were delivered after preterm labor or preterm PROM, and the remaining 146 were delivered with other indications described in a previous publication.13 Of these 358 deliveries, 60 were multiple gestations (55 twins, five triplets).
|
Placental chorioamnionitis was diagnosed in 164 of the 287 subjects, and this group comprised the study group. The 123 subjects who did not meet criteria for histopathologic chorioamnionitis were the controls. Of the 164 study subjects, 139 (85%) survived during the study period. One hundred (72%) of these 139 had Bayley developmental index scores administered at 7 months of corrected age. Of the 123 control subjects, 104 (85%) survived. Of these 104 subjects, 67 (64%) had 7-month testing done. The difference in 7-month follow-up rates of the cases and controls did not reach statistical significance.
Antepartum characteristics are shown in Table 1. Maternal age and socioeconomic scores were similar between groups. Gravidity and parity were higher in the study group. More women in the study group delivered after preterm PROM, received antenatal antibiotics, and had clinical chorioamnionitis. Table 2 summarizes delivery characteristics. Median gestational age and birth weight were lower and duration of ruptured membranes was longer in the chorioamnionitis group, whereas control infants were more likely to be male and the product of a multiple gestation. The frequencies of cesarean delivery and SGA infants were similar in both groups.
|
|
. The groups were not statistically different in all respects except for intraventricular hemorrhage of any grade (relative risk [RR] = 1.6, 95% confidence interval [CI] 1.1, 2.4, P = .013). Intraventricular hemorrhage grades 3 and 4 (RR = 1.8, CI 0.8, 3.9, P = .16) and neonatal sepsis (RR = 5.3, CI 0.7, 42.1, P = .14) occurred more frequently in the case group, although it did not reach statistical significance. The relationship between histopathologic chorioamnionitis and intraventricular hemorrhage remained statistically significant (P = .045) when examined in a logistic regression model controlling for multiple gestation, gender, preterm labor or preterm PROM, antibiotic use, birth weight, and gestational age.
|
, in the control group, the frequency of intraventricular hemorrhage of all grades and of grades 3 or 4 were similar between infants with 7-month follow-up compared with those without follow-up. In the study group, intraventricular hemorrhage of all grades occurred with a higher frequency in infants without follow-up compared with infants with follow-up. Grade 3 or 4 intraventricular hemorrhage was also more common in these infants.
|
). Adjusting for intraventricular hemorrhage, multiple gestation, gender, preterm labor or preterm PROM, antibiotic use, birth weight, gestational age, and duration of ruptured membranes did not substantially alter these results. Categorical analysis showed a similar percentage of infants in both groups with suspected and diagnosed developmental delay. Regression analysis did not significantly alter the bivariate analysis of Bayley score means presented in Table 5.
|
and 5 were repeated with regrouping the 26 control subjects with grade 1 membrane and grade 0 umbilical cord inflammation into the case group. The results were consistent with those presented in the original analysis. We also obtained consistent results when a similar repeat analysis was done after removing the nine subjects with clinical chorioamnionitis from the control group. |
Discussion |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
Other secondary outcomes in the present study, including low Apgar scores, grade 3 and 4 intraventricular hemorrhage, bronchopulmonary dysplasia, respiratory distress syndrome, and sepsis occurred more frequently in the study subjects compared with controls. However, these differences did not reach statistical significance. Given the modest size of our study population, the possibility of a type 2 error must be considered.
In case subjects, the lack of 7-month follow-up was associated with intraventricular hemorrhage in the neonatal intensive care unit. Because of this, although the initial study cohort had a higher rate of intraventricular hemorrhage in the chorioamnionitis group, this difference was not present in the study subjects who were followed up at 7 months. Although this might have biased the chorioamnionitis group to have better developmental testing scores, regression analysis that adjusted for multiple factors including intraventricular hemorrhage also found no difference.
The etiology of adverse neonatal outcome for infants delivered with chorioamnionitis might be directly from fetal and neonatal infection. It is also possible that inflammation impairs placental function. Johnston et al17 reported a significant decrease (46% compared with 75%, P < .05) in histopathologic chorioamnionitis in patients assigned to the treatment arm in a randomized, double-masked trial of the use of antibiotics in women with PROM before 35 weeks. Gibbs et al18 demonstrated that antepartum antibiotic use in a randomized study of patients with clinical chorioamnionitis was associated with improved neonatal outcome. Improved placental function could effect this improved outcome by decreasing placental inflammation. The more frequent use of maternal antibiotics in 54% of subjects in the chorioamnionitis group might have biased our study by improving their outcome at 7 months of age. However, antibiotic use was included in our regression model, and this did not change the relationship between chorioamnionitis and outcome at 7 months.
We found that 57% of placentas in our study had evidence of chorioamnionitis. This is consistent with previous studies of this gestational age range. In the present study, which covered a narrow range of birth weights, mean gestational age and birth weight were lower for infants with placental chorioamnionitis. Although these differences were statistically significant, the differences were not large and might not be clinically significant. However, this finding supports previous data indicating that chorioamnionitis is associated with younger gestational age. The difference in gestational age could also have contributed to the increased risk of intraventricular hemorrhage associated with chorioamnionitis, because the frequency of this complication is higher with younger gestational age. However, despite analysis with a regression model including gestational age, the significant relationship between chorioamnionitis and intraventricular hemorrhage remained.
|
Footnotes |
|---|
Received August 23, 1999. Received in revised form January 27, 2000. Accepted February 10, 2000.
|
References |
|---|
|
Top
AbstractMaterials and MethodsResultsDiscussionReferences |
|---|
2. Mueller-Heubach E, Rubinstein DN, Schwarz SS. Histologic chorioamnionitis and preterm delivery in different patient populations. Obstet Gynecol 1990;75:622–6.
3. Svensson L, Ingemarsson I, Mardh P. Chorioamnionitis and the isolation of microorganisms from the placenta. Obstet Gynecol 1986;67:403–9.[Medline]
4. Hillier SL, Martius J, Krohn M, Kiviat N, Holmes KK, Eschenbach DA. A case-control study of chorioamnionic infection and histologic chorioamnionitis in prematurity. N Engl J Med 1988;319: 972–8.[Abstract]
5. Hardt NS, Kostenbauder M, Ogburn M, Behnke M, Resnick M, Cruz A. Influence of chorioamnionitis on long-term prognosis in low birth weight infants. Obstet Gynecol 1985;65:5–10.
6. Morales WJ. The effect of chorioamnionitis on the developmental outcome of preterm infants at one year. Obstet Gynecol 1987;70: 183–6.
7. Russell P. Inflammatory lesions of the human placenta. I. Clinical significance of acute chorioamnionitis. Am J Diagn Gynecol Obstet 1979;1:127–37.
8. Zhang J, Kraus FT, Aquino TI. Chorioamnionitis: A comparative histologic, bacteriologic, and clinical study. Int J Gynecol Pathol 1985;4:1–10.[Medline]
9. Ballard JL, Khoury JC, Wedig K, Wang L, Eilers-Walsman BL, Lipp R. New Ballard score, expanded to include extremely premature infants. J Pediatr 1991;119:417–23.[Medline]
10. Lubchenco LO, Hansman C, Dressler M, Boyd E. Intrauterine growth as estimated from liveborn birth weight data at 24 to 42 weeks of gestation. Pediatrics 1963;32:793–800.
11. Bayley N. Bayley scales of infant development. New York: Psychological Corporation, 1969.
12. Bayley N. Bayley scales of infant development II. San Antonio, Texas: Psychological Corporation, 1993.
13. Dexter SC, Malee MP, Pinar H, Hogan JW, Carpenter MW, Vohr BR. Influence of chorioamnionitis on developmental outcome in very low birth weight infants. Obstet Gynecol 1999;94:267–73.
14. 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]
15. Salafia CM, Minior VK, Rosenkrantz TS, Pezzullo JC, Popek EJ, Cusick W, et al. Maternal, placental, and neonatal associations with early germinal matrix/intraventricular hemorrhage in infants born before 32 weeks’ gestation. Am J Perinatol 1995;12:429–36.[Medline]
16. Grether JK, Nelson KB. Maternal infection and cerebral palsy in infants of normal birth weight. JAMA 1997;278:207–11.[Abstract]
17. Johnston MW, Sanchez-Ramos LS, Vaughn AJ, Todd MW, Benrubi GI. Antibiotic therapy in preterm premature rupture of the membranes: A randomized, prospective, double-blind trial. Am J Obstet Gynecol 1990;163:743–7.[Medline]
18. Gibbs RS, Dinsmoor MJ, Newton ER, Ramamurthy RS. A randomized trial of intrapartum versus immediate postpartum treatment of women with intraamniotic infection. Obstet Gynecol 1988;72: 823–8.
This article has been cited by other articles:
|
|
 |
|
  S. Polam, A. Koons, M. Anwar, S. Shen-Schwarz, and T. Hegyi Effect of Chorioamnionitis on Neurodevelopmental Outcome in Preterm Infants Arch Pediatr Adolesc Med, November 1, 2005; 159(11): 1032 - 1035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Yang, D. R. Taylor, H. H. Kaufman, R. Hume, and B. Calhoun Maternal and Fetal Outcomes of Spontaneous Preterm Premature Rupture of Membranes J Am Osteopath Assoc, December 1, 2004; 104(12): 537 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.E. Lee, E.H. Ha, H.S. Park, Y.J. Kim, Y.C. Hong, H. Kim, and J.T. Lee Exposure to air pollution during different gestational phases contributes to risks of low birth weight Hum. Reprod., March 1, 2003; 18(3): 638 - 643. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
