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Preterm premature rupture of the membranes compli-cates approximately 3% to 5% of all births in the UnitedStates, yet it accounts for a disproportionate amount ofall neonatal morbidity and mortality.1-3 Furthermore,preterm premature rupture of the membranes is associ-ated with an increased risk of acquiring perinatal infec-tions including chorioamnionitis, endometritis, andneonatal sepsis.1-6 It has been hypothesized that this asso-ciation with infection may be related to preexisting bac-terial invasion or to the presence of pathogens in thevagina that ascend into the amniotic cavity after disrup-tion of the amniotic membrane barrier.6-9 It has also been

proposed that amniotic fluid possesses certain bacterio-static properties that protect against potential infectiousprocesses and that a decrease in amniotic fluid volumemay impair the gravid woman’s ability to combat such in-fections.10

This latter hypothesis was tested by Vintzileos et al,10

who categorized patients with preterm premature rup-ture of the membranes into 2 groups on the basis of theultrasound measurement of the single deepest verticalpocket of residual amniotic fluid. These investigatorsdemonstrated that patients with oligohydramnios, de-fined as a single deepest vertical pocket of <1 cm, were atgreater risk of having chorioamnionitis and subsequentsepsis in the neonate. This earlier study had several limi-tations. First, the investigators used measurement of thesingle deepest vertical pocket rather than a potentiallymore sensitive measurement: the 4-quadrant amnioticfluid index (AFI). Second, patients in this earlier studydid not receive antibiotic prophylaxis or antenatally ad-ministered corticosteroids—currently considered thestandard of care and known to influence perinatal infec-tious outcome.11-17 Therefore, by the incorporation of

From the Department of Obstetrics and Gynecology, Medical Universityof South Carolina.John R. McCain Presentation, presented at the Sixty-second AnnualMeeting of The South Atlantic Association of Obstetricians and Gyne-cologists, St Petersburg, Florida, January 22-25, 2000.Reprint requests: Stephen T. Vermillion, MD, Department of Obstetricsand Gynecology, Medical University of South Carolina, 96 JonathanLucas St, Suite 634, Charleston, SC 29425.Copyright © 2000 by Mosby, Inc.0002-9378/2000 $12.00 + 0 6/6/107653doi:10.1067/mob.2000.107653

Amniotic fluid index values after preterm premature rupture ofthe membranes and subsequent perinatal infection

Stephen T. Vermillion, MD, Austin M. Kooba, MD, and David E. Soper, MD

Charleston, South Carolina

OBJECTIVE: Our purpose was to determine whether an amniotic fluid index (AFI) <5 cm after preterm premature rupture of the membranes is associated with an increased risk of perinatal infection.STUDY DESIGN: We performed a nonconcurrent prospective analysis of 225 singleton pregnancies compli-cated by preterm premature rupture of the membranes, with delivery between 24 and 32 weeks’ gestation.All included patients received 2 doses of betamethasone antenatally, in the first 24 hours after admission,and broad-spectrum antibiotic prophylaxis. Patients were categorized into 2 groups on the basis of a 4-quad-rant AFI <5 cm (n = 131) or ≥5 cm (n = 94). Perinatal outcomes analyzed included latency until delivery,mode of delivery, and frequencies of clinical chorioamnionitis, postpartum endometritis, and culture-provedearly neonatal sepsis. Continuous data were evaluated for normal distribution and tested for significance withthe Student t test. Categoric data were tested with the χ2 and Fisher exact tests. Multiple logistic regressionanalyses were performed with chorioamnionitis, endometritis, and early-onset neonatal sepsis each as thedependent variable in separate analyses. All 2-sided P values < .05 were considered significant.RESULTS: Both groups were similar with respect to selected demographics, gestational age at rupture of the membranes, birth weight, and maternal group B streptococcal colonization. Patients with an AFI <5 cmdemonstrated a shorter mean latency until delivery (5.5 ± 4.0 vs 14.1 ± 5.2) (mean ± SD) days (P = .02),greater frequency of amnioinfusion therapy (23.6% vs 5.3%) (P < .001), and cesarean delivery for nonreas-suring fetal testing (18.3% vs 4.3%) (P = .01). Multiple logistic regression analysis showed that an AFI <5 cmwas the only significant risk factor independently associated with early-onset neonatal sepsis (P = .004) andchorioamnionitis (P = .024).CONCLUSIONS: An AFI <5 cm after preterm premature rupture of the membranes between 24 and 32weeks’ gestation is associated with an increased risk of perinatal infection and a shorter latency precedingdelivery. (Am J Obstet Gynecol 2000;183:271-6.)

Key words: Amniotic fluid index, premature rupture of the membranes, perinatal infection

current antibiotic and corticosteroid therapies, our pur-pose was to determine whether patients with preterm pre-mature rupture of the membranes and oligohydramnios,defined as a 4-quadrant AFI <5 cm, are at an increasedrisk of having perinatal infection.

Material and methods

Inclusion and exclusion criteria. We performed a non-concurrent prospective study of infants delivered be-tween 24 and 32 weeks’ gestation after preterm prema-ture rupture of the membranes. Data were collected andentered into a validated, research-quality perinatal data-base at the Medical University of South Carolina betweenJanuary 1995 and December 1998. At admission, amnior-rhexis was confirmed by either the fern test, Nitrazinepaper testing, or gross pooling of amniotic fluid in thevagina or by a combination of these. Rectovaginal speci-mens were obtained from all patients for culture of groupB streptococci, and tests were performed for Chlamydiainfection and gonorrhea. All patients received antibioticprophylaxis consisting of ampicillin or clindamycin pluserythromycin or azithromycin for 7 days after admission.Patients who had positive cultures for group B strepto-cocci received additional intrapartum prophylaxis con-sisting of ampicillin or clindamycin. Chlamydia infectionand gonorrhea, if present, were appropriately treated. Atadmission, all patients had an ultrasonographic examina-tion, which included confirmation of the estimated ges-tational age, estimated fetal weight, and a cumulative 4-quadrant AFI measurement, as previously described byPhelan et al.18 All patients received a single course of be-tamethasone, consisting of two 12-mg injections duringthe first 24 hours after admission. Fetal surveillance in-corporated daily nonstress testing. For fetuses with non-reassuring nonstress test results, biophysical profile as-sessments were performed. Indications for deliveryincluded labor, the diagnosis of chorioamnionitis, or non-reassuring fetal test results. Fetal lung maturity assess-ment by either amniocentesis or vaginal fluid collectionwas not routinely performed during the study period andwas not incorporated into the indications for delivery. Pa-tients with clinical chorioamnionitis or nonreassuringfetal status at initial admission were excluded. Addition-ally, any patients with repeated corticosteroid therapy, a cerclage in situ, a growth-restricted or anomalous fetus,insulin-requiring diabetes, tocolytic exposure after rup-ture of membranes, or delivery within 24 hours of admis-sion were not included in the analysis.

Variables analyzed. Eligible patients were subsequentlycategorized into 2 groups on the basis of the admissionAFI measurement. Patients in group 1 were those witholigohydramnios quantified as an AFI <5 cm, whereasthose in group 2 had an AFI ≥5 cm. The 2 groups werecompared for demographic characteristics, the estimatedgestational age at both rupture of the membranes and

delivery, latency until delivery, mode of delivery, birthweight, maternal group B streptococcal status, the devel-opment of clinical chorioamnionitis, postpartum en-dometritis, and early-onset neonatal sepsis.

Definitions. Clinical chorioamnionitis was defined as 3 of 4 of the following signs in the absence of othercausative factors: maternal fever (>100.4°F), uterine ten-derness, maternal tachycardia (>120 beats/min), andfetal tachycardia (>160 beats/min). The diagnosis ofpostpartum endometritis was made on the basis of thepresence of maternal fever (>100.4°F) and uterine ten-derness documented on 2 occasions at least 6 hours apartafter an initial 24-hour observation period. Additionally,the exclusion of other potential infectious sources was es-sential for the diagnosis of endometritis. Early-onsetneonatal sepsis was defined as sepsis in a neonate withpositive culture results on either blood or cerebrospinalspecimens collected within the first 48-hours of life andbefore antibiotic administration. The 48-hour time inter-val was used to differentiate those neonates with potentialperipartum transmission versus those with nosocomiallyacquired infections.

Statistical analyses. Categoric data were tested for signif-icance with the χ2 and Fisher exact tests. Continuous datawere evaluated for normal distribution and tested for sig-nificance with the Student t test. To determine the con-founding effect of multiple variables, we performed 3 mul-tiple regression analyses. Variables that were consideredrisk factors for early-onset neonatal sepsis, endometritis,and chorioamnionitis were included. Early-onset neonatalsepsis, endometritis, and chorioamnionitis were eachtreated as the dependent variable in separate analyses. All2-sided P values < .05 were considered significant.

Results

Maternal and neonatal variables. A total of 225 patientswith preterm premature rupture of the membranes wereincluded in the study; 131 were included in group 1 (AFI<5 cm) and 94 in group 2 (AFI ≥5 cm). The 2 groups weresimilar with respect to maternal age, race, parity, insur-ance status, and maternal colonization with group Bstreptococci (Table I). Although both groups were simi-lar with respect to gestational age at rupture of mem-branes, those in group 1 demonstrated a significantlyshorter mean latency until delivery and were delivered atan earlier mean gestational age in comparison with pa-tients in group 2. Birth weights, however, were not signif-icantly different between the 2 groups. Both groups hadsimilar proportions of vaginal deliveries; however, ingroup 1 cesarean delivery was more likely to be per-formed because of nonreassuring fetal status (Table II).

Maternal and neonatal infectious outcome variables.Univariate analysis demonstrated that patients in group 1had a significant increase in the frequency of clinicalchorioamnionitis (P < .001) and postpartum endometri-

272 Vermillion, Kooba, and Soper August 2000Am J Obstet Gynecol

tis (P < .001). Similarly, neonates born to the patients ingroup 1 demonstrated a significant increase in the fre-quency of early-onset neonatal sepsis (P = .034) (TableIII). In the multiple logistic regression analyses incorpo-rating risk factors for perinatal infection, an AFI <5 cmwas the only risk factor that demonstrated a significant in-dependent association with early-onset neonatal sepsis (P = .004) and clinical chorioamnionitis (P = .024). How-ever, the diagnosis of postpartum endometritis was signif-icantly associated with both chorioamnionitis (P < .001)and cesarean delivery for nonreassuring fetal status (P =.002) regardless of AFI.

Comment

In our study the finding of an AFI <5 cm after pretermpremature rupture of the membranes was associated withthe development of chorioamnionitis and early-onsetneonatal sepsis. The concept that oligohydramnios after

preterm premature rupture of the membranes is associ-ated with perinatal morbidity and death is not a new one.Several studies have implicated oligohydramnios in pa-tients with preterm premature rupture of the membranesas a significant risk factor for perinatal infection, fetal dis-tress, cesarean delivery, and neonatal death.6, 10, 19

Vintzileos et al10 confirmed an increased risk of chorioam-nionitis, a shorter latency until delivery, cesarean delivery,and neonatal sepsis in patients with oligohydramniosafter rupture of the membranes. Significant differencesbetween that study and ours were that all patients in ourstudy population received corticosteroids antenatally andantibiotic prophylaxis. Both of these therapies are nowconsidered the standard of care in the setting of pretermpremature rupture of the membranes at gestational agesof ≤32 weeks. The multiple benefits of antenatal adminis-tration of corticosteroids for preterm neonates outweighthe concerns of potential infection risks after cortico-

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Table I. Demographic comparisons between groups with preterm premature rupture of membranes

Characteristic AFI <5 cm (n = 130) AFI ≥5 cm (n = 93) Statistical significance*

Maternal age (y, mean ± SD) 24.8 ± 5.2 24.3 ± 4.9 NSAfrican-American 94 (72%) 63 (78%) NSCaucasian 35 (27%) 29 (31%) NSMultiparous 56 (43%) 45 (48%) NSMedicaid funding 115 (88%) 79 (85%) NSMaternal group B streptococci 25 (19%) 19 (21%) NS

NS, Not significant.*P values were determined by Student t test for comparison of means for continuous variables and by χ2 test for comparison of cate-

goric variables. Two-sided P < .05 was considered significant.

Table II. Delivery characteristic comparisons between groups with preterm premature rupture of membranes

Characteristic AFI <5 cm (n = 131) AFI ≥5 cm (n = 94) Statistical significance*

Gestational age at membrane rupture (wk, mean ± SD) 27.7 ± 2.0 28.7 ± 1.8 NSLatency (d, mean ± SD) 5.5 ± 4.0 14.1 ± 5.2 P = .02Gestational age at delivery (wk, mean ± SD) 28.5 ± 2.0 30.7 ± 1.6 P = .04Birth weight (g, mean ± SD) 1169 ± 332 1476 ± 306 NSAmnioinfusion 31 (23.6%) 5 (5.3%) P < .001Vaginal delivery 85 (64.9%) 65 (69.1%) NSCesarean delivery for nonreassuring fetal status 24 (18.3%) 4 (4.3%) P = .01

NS, Not significant.*P values were determined by the Student t test for comparison of continuous variables and by the χ2 test for comparison of categoric

variables. Two-sided P < .05 was considered significant.

Table III. Univariate analysis of perinatal infectious outcome comparisons between groups with preterm premature rup-ture of membranes

Odds ratio and 95% Statistical Outcome No. % No. % confidence interval significance*

Chorioamnionitis 40 30.5 7 7.5 5.5 (2.2-14.2) P < .001Endometritis 29 22.1 4 4.3 6.4 (2.0-22.4) P < .001Early-onset neonatal sepsis 11 8.4 1 1.1 8.5 (1.1-179.4) P = .034

*P values were determined by the Student t test for comparison of continuous variables and by the χ2 test for comparison of categoricvariables. Two-sided P < .05 was considered significant.

AFI <5 cm (n = 131) AFI ≥5 cm (n = 94)

steroid therapy in patients with preterm premature rup-ture of the membranes.13-15 Vermillion et al20 demon-strated that, in patients with preterm premature ruptureof the membranes, those who received a single antenatalcourse of betamethasone did not have a greater risk ofperinatal infectious complications than those who didnot receive corticosteroid therapy. However, patients inthat study who received weekly doses of prophylactic cor-ticosteroids had an increased risk of chorioamnionitisand neonatal sepsis. Recognizing the potential for addi-tional confounders from multiple dosing of corticoste-roids antenatally, we included only those patients who re-ceived a single course of betamethasone. Additionally, a recent mul-ticenter trial17 confirmed that the use of antibiotic pro-phylaxis after preterm premature rupture of the mem-branes increased the latency period until delivery anddecreased the risk of neonatal sepsis. Patients in ourstudy were treated by a similar protocol for potential im-provement of perinatal infectious outcomes.

Several studies have evaluated the association betweenoligohydramnios after rupture of the membranes and ce-sarean delivery for intrapartum fetal heart rate abnor-malities resulting from cord compression.10, 19 It is pre-sumed that the heart tracing abnormalities are due to theloss of the protective cushioning of the umbilical cord byamniotic fluid. The finding in our study that patients witholigohydramnios were more likely to undergo cesareandelivery because of nonreassuring fetal heart rate pat-terns is consistent with the findings of these other studies.

Internal monitoring with intrauterine pressurecatheters has been identified as a risk factor forchorioamnionitis and postpartum endometritis by previ-ous investigators.21 Although more patients in the oligo-hydramnios group were exposed to intrapartum am-nioinfusion therapy and thus to more internal catheters,amnioinfusion alone was not a significant risk factor forchorioamnionitis, endometritis, or early-onset neonatalsepsis in our multiple logistic regression analyses. Mona-han et al22 actually demonstrated a reduction in the riskof perinatal infection in patients receiving intrapartumamnioinfusion therapy. This is most likely the result of areduction in the overall microbial concentration in theamniotic cavity with amnioinfusion.

Although patients in the group with oligohydramnioshad a shorter latency until delivery and an increased fre-quency of chorioamnionitis, latency was not indepen-dently associated with chorioamnionitis. Other investiga-tors have demonstrated an association between thedevelopment of chorioamnionitis and a shorter latencyin patients with ruptured membranes.10 This is consistentwith the concept that preterm premature rupture of themembranes is due to a preexisting subclinical intra-amniotic infectious process that rapidly progresses tosymptomatic chorioamnionitis, resulting in a shorter la-

tency until delivery. Conversely, Soper et al21 previouslydemonstrated a direct relationship between longer dura-tion of ruptured membranes and intra-amniotic infectionthat is presumably the result of longer exposure to po-tential pathogens.

The identification of oligohydramnios, defined as anAFI <5 cm, in patients with preterm premature rupture ofthe membranes appears to indicate a significant risk ofchorioamnionitis and early-onset neonatal sepsis. Thesefindings can aid in the counseling of patients with pre-term premature rupture of the membranes and may haveseveral clinical applications. Perhaps these patients war-rant closer observation for early signs of chorioamnioni-tis, more frequent antenatal fetal testing, and more ag-gressive evaluation for neonatal sepsis. Further studiesare needed to address these questions.

REFERENCES

1. Johnson JW, Daikoku NH, Niebyl JR, Johnson TRB, KhouzamiVA, Witter RF. Premature rupture of the membranes and pro-longed pregnancy. Obstet Gynecol 1981;57:547-56.

2. Gibbs RS. Premature rupture of the membranes. Obstet Gy-necol 1982;60:671-9.

3. Mead PB. Management of the patient with premature rupture ofthe membranes. Clin Perinatol 1980;7:243-55.

4. Naeye RL. Causes of perinatal mortality in the US CollaborativePerinatal Project. JAMA 1977;238:228-9.

5. Lanier LR, Scarbrough RW, Ficklingim DW, et al. Incidence ofmaternal and fetal complications associated with rupture of themembranes before the onset of labor. Am J Obstet Gynecol1965;93:398-401.

6. Yoon BH, Kim YA, Romero R, Kim JC, Park KH, Kim MH, et al.Association of oligohydramnios in women with preterm prema-ture rupture of membranes with an inflammatory response infetal, amniotic, and maternal compartments. Am J Obstet Gy-necol 1999;181:784-8.

7. Romero R, Brody DT, Oyarzun, et al. Infection and labor. Inter-leukin-1: a signal for the onset of parturition. Am J Obstet Gy-necol 1989;160:1117-23.

8. Romero R, Durum S, Dinarello CA, Oyarzun E, Hobbins JC,Mitchell MD. Interleukin-1 stimulates prostaglandin biosynthe-sis by human amnion. Prostaglandins 1989;37:13-22.

9. Romero R, Manogue KR, Mitchell MD, Wu YK, Oyarzun E, Hob-bins JC, et al. Infection and labor. IV. Cachectin–tumor necrosisfactor in the amniotic fluid of women with intraamniotic infec-tion and preterm labor. Am J Obstet Gynecol 1989;161:336-41.

10. Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ. De-gree of oligohydramnios and pregnancy outcome in patientswith premature rupture of the membranes. Obstet Gynecol1985;66:162-7.

11. Collaborative Group on Antenatal Steroid Therapy. Effect of an-tenatal dexamethasone on the prevention of respiratory distresssyndrome. Am J Obstet Gynecol 1981;141:246-87.

12. Ohlsson A. Treatments of preterm premature rupture of themembranes: a meta-analysis. Am J Obstet Gynecol 1989;160:890-906.

13. Crowley PA, Chalmers I, Keirse MJ. The effects of corticosteroidadministration before preterm delivery: an overview of the evi-dence from controlled trials. Br J Obstet Gynaecol 1990;97:11-25.

14. Oyarzun E, Gomez R, Romero R, Bracken M. Preterm prema-ture rupture of the membranes: a meta-analysis of the effect ofsteroids on the prevention of respiratory distress syndrome. RevMed Chil 1991;119:388-95.

15. Effect of corticosteroids for fetal maturation on perinatal out-comes. NIH Consens Statement 1994 Feb 28–Mar 2;12(2):1-24.

16. Morales WJ, Diebel D, Lazar AJ, Zadrozny D. The effect of ante-natal dexamethasone administration on the prevention of respi-

274 Vermillion, Kooba, and Soper August 2000Am J Obstet Gynecol

ratory distress syndrome in preterm gestations with prematurerupture of the membranes. Am J Obstet Gynecol 1986;154:591-5.

17. Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, DasAF, Ramsey RD, et al. Antibiotic therapy for reduction of infantmorbidity after preterm premature rupture of the membranes: a randomized controlled trial. National Institute of Child Healthand Human Development Maternal-Fetal Medicine Units Net-work. JAMA 1997;278:989-95.

18. Phelan JP, Smith CV, Broussard P, Small M. Amniotic fluid vol-ume assessment with the four-quadrant technique at 36-42weeks’ gestation. J Reprod Med 1987;32:540-2.

19. Moberg LJ, Garite TJ, Freeman RK. Fetal heart rate patterns offetal distress in patients with preterm premature rupture of themembranes. Obstet Gynecol 1984;64:60-4.

20. Vermillion ST, Soper DE, Chasedunn-Roark J. Neonatal sepsisafter betamethasone administration to patients with pretermpremature rupture of membranes. Am J Obstet Gynecol1999;181:320-7.

21. Soper DE, Mayhall CG, Dalton HP. Risk factors for intraamnioticinfection: a prospective epidemiologic study. Am J Obstet Gy-necol 1989;161:562-8.

22. Monahan E, Katz VL, Cox RL. Amnioinfusion for preventing puer-peral infection: a prospective study. J Reprod Med 1995;40:721-3.

DiscussionDR CAROLYN S. WILSON, Winchester, Virginia. It is 3 o’-

clock in the morning on January 2, and I have been asleepabout 1 hour. The nurse wakes me up and tells me that apatient just came to the labor and delivery suite becauseher water broke at midnight. The patient denies contrac-tions or bleeding and has good fetal heart tones. I am notalarmed, and I consider going back to sleep. In answer tomy query, the nurse states that the patient’s due date is “theend of April.” My mood immediately changes, and I getout of bed. In the examination room, the patient is notedto have gross rupture of membranes, and I perform an ul-trasonographic examination. Thankfully, the fetus is in ver-tex presentation and has an estimated fetal weight of 700 g,but there is no measurable amniotic fluid.

Preterm premature rupture of membranes is relatedto an increased incidence of perinatal morbidity anddeath.1 Patients with preterm rupture of membranes andoligohydramnios have previously been shown to havehigher rates of clinical chorioamnionitis and neonatalsepsis than those with normal amniotic fluid volume.2

It has been proposed that the microbial invasion ofthe amniotic cavity associated with preterm prematurerupture of membranes is caused by an impaired naturalimmunity, because amniotic fluid has antimicrobial activ-ity. A reduced volume may decrease this activity and pre-dispose the patient to an ascending intrauterine infec-tion.3 In 1999, Yoon et al3 found that women withpreterm premature rupture of membranes had evidenceof inflammatory responses in the fetal, amniotic, and ma-ternal tissues. It is of interest that microbial invasion ofthe fetal compartment can cause fetal inflammatory syn-drome.4 This is a multisystem condition that affects thefetal adrenal gland and kidneys. The oligohydramniosmay be a host response to microbial invasion, and it is un-clear whether this precedes or is a result of rupturedmembranes.

Vintzileos et al2 studied the relationship between in-fection and preterm premature rupture of membraneswith oligohydramnios in 1985. In response to that study,

Vermillion, Kooba, and Soper reexamined this relation-ship but incorporated more recent practices of routineuse of corticosteroids and prophylactic antibiotics. Addi-tionally, they used the more accurate 4-quadrant tech-nique of obtaining an AFI.

The study was performed in South Carolina between1995 and 1998. It was a nonconcurrent prospective studyof 225 singleton pregnancies complicated by rupturedmembranes between 24 and 32 weeks’ gestation. Group 1had an AFI of <5 cm, and group 2 had an AFI of >5 cm.

The authors found a statistically significant increase inearly-onset neonatal sepsis and chorioamnionitis in pa-tients with preterm premature rupture of membranesand oligohydramnios. Additionally, these patients had ashorter latency to delivery, increased rates of amnioinfu-sion, and more cesarean deliveries for nonreassuringfetal heart rate patterns.

The statistical analysis was appropriate and thorough.The definitions of early-onset neonatal sepsis andchorioamnionitis were standard. Inclusion and exclusioncriteria were explained and results presented clearly.

In a review of the inclusion criteria for the study, sev-eral questions came to mind:

1. Specimens for culture of group B streptococci, Neis-seria gonorrhoeae, and Chlamydia were obtained. Was a wetmount preparation performed? Was the cervix digitallyexamined?

2. Patients received antibiotic prophylaxis with ampi-cillin, clindamycin, and erythromycin or azithromycin.Were the outcomes examined by culture positivity andantibiotic selection?

3. An ultrasonographic examination was performed onall patients. Was the fetal presentation considered in theanalysis and in the rate of cesarean deliveries? Was theAFI at admission confirmed by another observer? Was theAFI rechecked after hydration?

4. This interesting article has both clinical and basic sci-ence implications. Clinically, should patients with pre-term premature rupture of membranes and oligohy-dramnios be treated with more aggressive antibiotictherapy and increased fetal surveillance? What is the roleof amnioinfusion? Would amnioinfusion decrease the ce-sarean delivery rate for nonreassuring fetal heart rate pat-terns? What is the role of fetal fibronectin? Should thesepatients have tocolysis?

5. On a basic science level, what is the pathogenesis ofan increased inflammatory response in patients with pre-term premature rupture of membranes and oligohy-dramnios? Could agents be developed to affect the im-mune response before membrane rupture?

I look forward to Dr Kooba’s comments and hope thatfurther research in this area can shed new light on thisproblem.

REFERENCES

1. Vermillion ST, Soper DE, Chasedunn-Roark J. Neonatal sepsisafter betamethasone administration to patients with preterm

Volume 183, Number 2 Vermillion, Kooba, and Soper 275Am J Obstet Gynecol

premature rupture of membranes. Am J Obstet Gynecol1999;181:320-7.

2. Vintzileos AM, Campbell WA, Nochimson DJ, Weinbaum PJ. De-gree of oligohydramnios and pregnancy outcome in womenwith preterm premature rupture of membranes. Obstet Gynecol1985;66:162-7.

3. Yoon BH, Young AN, Romero R, Kim JC, Park KH, Kime MH, etal. Association of oligohydramnios in women with preterm pre-mature rupture of membranes with an inflammatory responsein fetal amniotic and maternal compartments. Am J Obstet Gy-necol 1999;181:784-8.

4. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM.The fetal inflammatory response syndrome. Am J Obstet Gy-necol 1998;179:194-202.

DR ED HORGER, Columbia, South Carolina. Dr Kooba,I am particularly interested in your final conclusion orrecommendation that a more aggressive antibiotic pro-phylaxis may be appropriate for those individuals withsignificant oligohydramnios. Could you give us any fur-ther recommendation as to what you may be doing in thisregard now?

DR JOHN SCOTT, Spartanburg, South Carolina. I have aclinical question. It was stated that 3 of 4 criteria areneeded to diagnose chorioamnionitis—maternal temper-ature >100.4°F, maternal tachycardia, fetal tachycardia,and uterine tenderness. In clinical practice most of thepatients laboring with clinical chorioamnionitis have anepidural injection, so uterine tenderness cannot be usedvery well. That is different for the patient who is not inlabor, but I wondered whether the 3 of 4 criteria appliedto patients in labor with epidural anesthesia, as well as topatients who are not in labor.

DR DAVID ARCHER, Norfolk, Virginia. This is not myarea of expertise, but I wish to ask a simple question. Hasanyone ever looked at the reaccumulation of amnioticfluid to indicate whether there is a defect in the mem-branes that prevents the reaccumulation?

DR KOOBA (Closing). First, I thank Dr Wilson for herkind review of our article, and I shall address her ques-tions first.

Digital examinations and cervicovaginal wet-prepara-tion examinations were not routinely performed at admis-sion. Any patients with documented digital examinationsbefore the onset of labor were excluded from our studysample. All patients with preterm premature rupture ofthe membranes received broad-spectrum antibiotic cover-age based on the data by Mercer et al (see reference 17 ofarticle). Before 1997, all patients with preterm premature

rupture of the membranes received a 2-day course of par-enterally administered ampicillin, followed by 5 days oforally administered amoxicillin concomitantly with 7 daysof orally administered erythromycin. From 1997 onward,azithromycin was substituted for erythromycin as standardprotocol in preterm premature rupture of the mem-branes at the study institution. Any patients colonized withgroup B streptococci received intrapartum doses of ampi-cillin or clindamycin for prophylaxis. Cultures positive forChlamydia and N gonorrhoeae were rare and were treatedappropriately. Both groups were similar with respect tothe frequencies of maternal colonization by group B strep-tococci. Further multiple logistic regression analysis wasunable to demonstrate an independent association be-tween positivity for group B streptococci and any of theadverse perinatal outcomes. All infants with nonvertexpresentations in our study sample were delivered by ce-sarean procedure. There was no difference in the rate ofcesarean delivery for nonvertex presentation between the2 groups. AFI evaluations were performed by a junior res-ident, with confirmation by either the attending physicianor the chief resident on call. The AFI was not routinely reassessed after hydration once amniorrhexis was con-firmed.

With regard to Dr Horger’s question, the finding of anAFI <5 cm may be added as an additional risk factor intothe neonatal sepsis workup protocol. Those neonatesperhaps could have more vigilant evaluations for earlydetection of septicemia and prompt antibiotic coverage.Additionally, a lowered threshold for initiating broad-spectrum intrapartum antibiotic therapy could be insti-tuted for those women with only a few signs of chorioam-nionitis and an AFI <5 cm, as Dr Scott has mentioned. Forstandardization of the outcomes, the definitions werestrictly used in that 3 of 4 of the listed signs for chorioam-nionitis were essential for the diagnosis. Of note, the ma-jority of the cases of chorioamnionitis were diagnosed be-fore intrapartum epidural placement.

Finally, for Dr Archer’s question regarding the reaccu-mulation of amniotic fluid after preterm premature rup-ture of the membranes, we specifically did not evaluate thepossibility of reaccumulation of amniotic fluid after the ini-tial AFI determination at admission. I am aware of only onepublished abstract evaluating daily AFI assessments afterpreterm premature rupture of the membranes. Those in-vestigators noted that the mean AFI at admission was es-sentially unchanged on the day of delivery.

276 Vermillion, Kooba, and Soper August 2000Am J Obstet Gynecol