# Postoperative Infectious Morbidities of Cesarean Delivery in Human Immunodeficiency Virus-Infected Women

Authors: Helen Cavasin; Thao Dola; Olga Uribe; Manoj Biswas; Mai Do; Azad Bhuiyan; MarkAlain Dery; Chi Dola
Journal: Infectious Diseases in Obstetrics and Gynecology
 (2009)

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## Abstract

Objective. To compare the infectious complication rates from cesarean delivery of human immunodeficiency virus (HIV)-infected women and HIV-negative women. Materials and Methods. A retrospective analysis was performed on data derived from HIV-infected women and HIV-negative women, who underwent cesarean delivery at two teaching hospitals. Main outcome measures were infectious postoperative morbidity. Descriptive, comparison analysis, and multiple logistic regression analysis were performed. Results. One hundred and nineteen HIV-infected women and 264 HIV-negative women delivered by cesarean section and were compared. The HIV-negative women were more likely than the HIV-infected women to deliver by emergent cesarean section (78.0% versus 51.3%, resp., P<.05), to labor prior to delivery (69.4% versus 48.3%, resp., P<.01), and to have ruptured membranes prior to delivery (63.5% versus 34.8%, resp., P<.05). In bivariate analysis, HIV-infected and HIV-negative women had similar rates of post-operative infectious complications (16.8% versus 19.7%, resp., P>.05). In a multivariate stepwise logistic analysis, emergent cesarean delivery and chorioamnionitis but not HIV infection were associated with increased rate of post-operative endometritis (odds ratio (OR) 4.10, 95% confidence interval (95% CI) 1.41–11.91, P<.01, and OR 3.02, 95% CI 1.13–8.03, P<.05, resp.). Conclusion. In our facilities, emergent cesarean delivery and chorioamnionitis but not HIV infection were identified as risk factors for post-operative endometritis.


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## Body

## 1. Introduction

The original landmark study, PACTG 076 reported a
decrease in the vertical transmission of human immunodeficiency virus (HIV)
infection from mother to child from 25% to 8% with the use of zidovudine in the
antenatal, intrapartum, and neonatal periods [1]. More recently,
cesarean section has been recommended in women with viral load above 1000 copies/mL
to further prevent vertical transmission of HIV [2].  While there are many
studies supporting the benefits of the combination of cesarean delivery and
antiretroviral medications in preventing vertical transmission of HIV disease
from mother to child [3–8], there are also reports on the morbidities that HIV-infected women
incurred from surgical procedures [9–11]. Previous reports on the morbidities of
cesarean deliveries implied that even healthy, nonimmunodeficient women could
sustain significant complications [12, 13].  Thus, it would appear that
HIV-infected women may have even more post-operative complications, especially
the infectious morbidities, due to their immunodeficient status when they
underwent cesarean delivery in an attempt to decrease vertical transmission of
the HIV disease.Current available data reported
conflicting results with regard to the post-operative morbidities experienced
by HIV-infected women [4, 9–11, 14, 15], therefore, we undertook this
study to further examine and compare the infectious complication rate from
cesarean delivery of HIV-infected women with those of HIV negative women.


## 2. Materials and Methods

A retrospective analysis was
performed on data obtained from women who presented at two teaching medical
institutions, the Medical Center of Louisiana at New Orleans - University Campus and Tulane
Health Sciences Center, and who subsequently underwent a cesarean section.  This study was approved by the Institutional
Review Board.  Identification of the
study patients (HIV-infected women) was obtained by reviewing the labor and
delivery log.  Their available medical
records were reviewed for data abstraction. Control subjects were
HIV-seronegative women who delivered by cesarean section during the same time
period and whose medical records were available for review.Medical records were reviewed and
data was collected on maternal demographics, number of previous cesarean
deliveries, estimated gestational age at time of delivery, classification of
cesarean delivery as elective or emergent, pre-operative hematocrit values on
the day of delivery, membrane status, application of internal monitoring
device, type of anesthesia, skin incision, uterine incision, operative time,
estimated blood loss, post-operative morbidities, HIV status, CD4 lymphocyte count, and viral
load.For this study, elective cesarean delivery was defined as
a planned operation without signs of labor prior to surgery.  Emergent cesarean delivery was defined as
surgery performed after the presence of regular uterine contractions with or
without rupture of membranes and for maternal and/or fetal indications, such as
nonreassuring fetal heart rate status, arrest disorders, and third trimester
bleeding.Post-operative infectious morbidities that were evaluated
in this study included endometritis
(defined as temperature elevation above38°C with uterine
tenderness and requiring antibiotics treatment in the absence of other etiology
for the fever), urinary tract infection, septic pelvic thrombophlebitis,
pneumonia, and superficial or deep wound breakdown at the time of discharge
from the hospital.At the
above teaching institutions, the management of the patients was conducted by
resident physicians under the supervision of Maternal-Fetal Medicine specialist
or general obstetrician with consultation from Maternal-Fetal Medicine
specialist as indicated.  The management
of patients was within the standard of current obstetric care.  All patients received prophylactic pre-operative
antibiotics.Data was
analyzed using SPSS-11 Software (SPSS Inc., Chicago, Ill.).  Chi-square analysis with Fischer exact when
necessary, Student’st-test, and multiple logistic regression analysis were
performed when appropriate. Statistical
significance was assumed at   P<.05.


## 3. Results

Over the study period, from July 1998 to December 2004,
119 HIV infected women delivered by cesarean section at the above two teaching
institutions.  Data was collected on 264
HIV-negative women who delivered by cesarean section during this time and served
as the controls. Maternal characteristics of the two groups are presented in Table1. Overall, the majority of the patients
were African American (92.1% of HIV-infected group and 84.3% of HIV-negative
group, P<.05).  Both groups
demonstrated a high body mass index (32.7±7.8 kg/m2 in
HIV-infected group versus 33.6±8.2 kg/m2 in HIV-negative group,
P>.05).  The CD4 lymphocyte
count and viral load near time of delivery of the HIV-infected group were
evaluated; 78.8% of the HIV-infected women had a CD4 lymphocyte
count of ≥200 and 19.2% had undetectable viral load (Table 1).Table 1
Maternal characteristics.
HIV-infectedHIV-negativeP-valueAge (years)24.6 ± 5.125.7±6.7NSRaceAfrican American105 (92.1%)210 (84.3%)<.05Others*9 (7.9%)39 (15.7%)<.05Maternal
weight (kg)88.9±23.189.8±23.2NSMaternal
height (m)1.6 ± .071.6 ± .07NSBMI (kg/m2)32.7±7.833.6±8.2NSMean CD
Count (n=80)455.0±277.9—Women withCD4         count ≥200 cells/mm363 (78.8%)Mean viral
load (copies/ml) (n=73)40,295.8 ± 115,448.8—Women with
undetectable viral load (<400 copies/ml)14 (19.2%)Data presented as number
and percent or mean ± standard deviation.NS = Not significant.Others* include:
Caucasian, Hispanic, and Asian.Obstetrical
characteristics of the two groups are compared in Table2.  There was no significant difference between
the HIV-infected group and the HIV-negative group in terms of gravidity,
parity, number of previous cesarean sections, estimated gestational age at time
of delivery, and rate of chorioamnionitis.
HIV-infected women were significantly more likely to have a lower
preoperative hematocrit than the HIV-negative women (31.9±3.8% versus 33.6±3.8%,
resp., P<.01).  HIV-negative
women were significantly more likely than HIV-infected patients to deliver by
emergent cesarean section (78.0% versus 51.3%, resp., P<.01), to labor
prior to delivery (69.4% versus 48.3%, resp., P<.01), to have ruptured membranes
prior to delivery (63.5% versus 34.8%, resp., P<.01), and to have
application of internal monitoring devices during labor (31.5% versus 6.0%,
resp., P<.01).Table 2
Obstetrical characteristics.
HIV-infectedHIV-negativeP-valueGravidity2.9±2.02.8±1.9NSParity1.6±1.81.4±1.6NSNo. of previous c/s064
(58.7%)146
(56.2%)NS128
(25.7%)61
(23.5%)NS212
(11.0%)34
(13.1%)NS33 (2.8%)13 (5.0%)NS41 (.9%)6 (2.3%)NS51 (.9%)0NSEGA at delivery (weeks)37.4±3.137.7±3.4NSPreoperative Hematocrit (%)31.9±3.833.6±3.8<.01Emergent cesarean delivery61
(51.3%)206
(78.0%)<.01Labor prior to delivery56
(48.3%)179
(69.4%)<.01Rupture of membranes prior to delivery40
(34.8%)165
(63.5%)<.01Use of internal monitor7 (6.0%)82
(31.5%)<.01Chorioamnionitis5 (4.3%)18 (6.8%)NSData
presented as mean ± standard deviation or number and percent.NS =
Not significant.The surgical characteristics of cesarean delivery in both
HIV-infected and HIV-negative women are presented in Table3.  Pfannenstiel skin incision were more often
performed in HIV-infected women than their controls (94.5% versus 82.7%,
resp., P<.01).  There was no
statistical difference in the other characteristics reviewed which included the
type of anesthesia, the type of uterine incision, the estimated blood loss
during surgery, or the operative time.
Postoperative infectious morbidities are presented in Table 4.  There was no significant difference in the
infectious morbidities between the HIV infected women and the control group. The
most common infectious morbidity after cesarean delivery for our study
population is postpartum endometritis.Table 3
Description of surgical procedures.
HIV-infectedHIV-negativeP-valueAnesthesiaGeneral10 (8.6%)30
(11.6%)NSRegional106
(91.4%)229
(88.4%)NSSkin IncisionPfannenstiel104
(94.5%)215
(82.7%)<.01Midline6 (5.5%)45 (17.3%)<.01Uterine IncisionLow transverse110
(95.7%)248
(94.7%)NSClassical/low transverse5 (4.3%)14 (5.3%)NSwith vertical extensionEstimated blood loss
(cc)857.4±311.2880.0±364.5NSOperative time (min)69.5±34.974.9±33.0NSData presented as mean ±
standard deviation or number and percent.NS = Not significant.Table 4
Postoperative
infectious complications among HIV-infected women and HIV-negative women.
HIV-infectedHIV-negativeP-valueInfectious complications20 (16.8%)52 (19.7%)NSEndometritis15 (12.6%)32 (12.1%)NSUrinary tract infection2 (1.7%)15 (5.7%)NSSuperficial wound
breakdown1 (0.8%)5 (1.9%)NSDeep wound breakdown1 (0.8%)3 (1.1%)NSSPT*05 (1.9%)NSPneumonia2 (1.7%)3 (1.1%)NSData presented as
number and percent.SPT* = Septic pelvic
thrombophlebitis.NS = Not significant.Furthermore, there
was no statistical significant difference between the mean ± SDCD4 lymphocyte count between the HIV-infected women with infectious morbidity and
those without infectious morbidity (413.2±257.9 cells/mm3 and 465.4±283.7 cells/mm3, resp., P>.05), and between the mean
± SD viral load of those with infectious morbidity and those without infectious
morbidity (26,967.1 ± 79,491.6 copies/ml and 43,7242.9 ± 123,389.8 copies/mL,
resp., P>.05).Postoperative infectious morbidity in both groups was analyzed
according to whether the cesarean section was an elective or emergent
delivery.  Both groups of women were
statistically more likely to experience postpartum endometritis when being
delivered by emergent cesarean section than by elective cesarean section, (21.3%
versus 3.4%, resp.,P<.05 in HIV-infected women and 14.6% versus 3.5%,
resp., P<.05 in HIV-negative women).Postpartum endometritis composed the majority of the
post-operative infectious morbidity, and HIV-negative women in our study had
significantly more obstetrics risk factors for postpartum endometritis than the
HIV-infected women. Those risk factors were: delivery by emergent cesarean
section, rupture of membranes and labor prior to delivery, and insertion of
internal monitoring. Because of that, we further performed logistic regression
analysis, controlling for these risk factors to determine whether HIV infection
play a significant role in postpartum endometritis. To identify risk factors
influencing the risk of postpartum endometritis, we constructed a stepwise
proportional odds model.  HIV infectious
status, emergent cesarean delivery, ruptured membranes prior to delivery,
application of internal monitoring devices during labor, chorioamnionitis, and
preoperative hematocrit were included in the model-building.  HIV infectious status, rupture of membranes
prior to cesarean delivery, application of internal monitoring devices during
labor, and preoperative hematocrit were not found to be significant predictors
of endometritis (P>.05).  However,
the odds of having endometritis were almost 4 times higher in emergent cesarean
delivery (odds ratio (OR) 4.1, 95% Confidence interval (CI) 1.41–1.91, P=.009) and 3 times higher in those
with chorioamnionitis during labor (OR 3.02, 95% CI 1.13–8.03, P=.027).  It should be noted that because colinearity
was present between labor prior to delivery by emergent cesarean section and
emergent cesarean delivery, we only included emergent cesarean delivery in the
multivariate stepwise logistic regression model (Table 5).Table 5
Risk factors
variables influencing postpartum endometritis in a stepwise oddsmodel.*
Riskfactors†EstimateOdds of postpartum endometritisP valueβSE‡OR‡95%CI‡Intercept−4.621.04——<.0001Emergent cesarean delivery1.410.544.101.41–11.91.009Chorioamnionitis1.100.503.021.13–8.03.027M*odel-building for
emergent cesarean delivery: β0 + β1 HIV status + β2 experienced rupture of membranes prior to cesarean delivery + β3 placement
of internal monitoring devices during labor + β4  Chorioamnionitis + β5 hematocrit +  β6 indication of cesarean delivery. R†eference group:
elective cesarean delivery, absence of chorioamnionitis.SE‡, Standard error; OR,
odds ratio; CI, confidence interval.


## 4. Discussion

According to our study, there was not a
significant difference in infectious postoperative morbidity in HIV infected
women who delivered by cesarean section when compared to their cohorts of
HIV-negative women. However, logistic regression analysis highlighted the
increased risk of postpartum endometritis in women who delivered by emergent
cesarean section and who had chorioamnionitis during labor, controlling for covariates
including HIV infectious status.  The HIV
infected women in this study were significantly less likely than the control
subjects to deliver by emergent cesarean delivery (51.3% versus 78.0%, resp.,P<.01) and should, therefore, have had a lower rate of postpartum
endometritis.  Since
we observed similar rates of postpartum endometritis in the two groups, despite
the fact that HIV-infected women had less risk factors for postpartum
endometritis, we can speculate that HIV infection may be a risk factor for
postpartum endometritis after cesarean section. However, because of the small
sample size, we do not find statistical evidence that HIV infection resulted in
higher infectious morbidity after cesarean delivery as reported in some previous
studies [8–11, 16–21]. A
possible explanation for our result is that we reported on a population of
HIV-infected women who were reasonably immunocompetent.  The mean ± SD CD4 lymphocyte
count of our study population was 455.0±277.9 and 78.8% had a CD4 lymphocyte count of at least 200 or greater.  Most studies reported the increased risk of
postoperative infectious morbidities to be associated with the severe degree of
immune suppression [9, 17].Stratified analysis by whether
cesarean delivery was emergent or elective in HIV infected women demonstrated
that emergent cesarean delivery increased postoperative endometritis over
elective cesarean delivery.  This is
consistent with previous studies which have also demonstrated the highest risk
of postoperative morbidity occurring in HIV-infected women who deliver by
emergent cesarean section [11, 20, 21].
Therefore
as an HIV-infected woman considers elective cesarean delivery or attempt at
vaginal delivery, our counseling should include the increased risk of
developing postoperative endometritis should her attempt at vaginal delivery
fail and emergent cesarean delivery become necessary.  We agreed with Marcollet’s recommendation
that women with a low probability of having a successful vaginal delivery
should consider scheduled cesarean delivery [14].  Current ACOG guidelines on recommending
elective cesarean delivery for HIV infected women to reduce vertical
transmission emphasize the importance of performing the surgery prior to the
onset of labor or rupture of membranes [2].
Cesarean delivery performed after the onset of labor or rupture of
membranes (i.e., Emergent cesarean delivery) is of unclear benefit with regard
to decreasing the vertical transmission risk [2]. Thus, it is important to adhere to the ACOG
recommendation on elective cesarean delivery for HIV-infected women as a mean
to further reduce vertical transmission rate, as the benefits of cesarean
delivery performed after labor or rupture of membranes is unknown and based on
current study and other reports [11, 14, 20, 21], maternal infectious morbidity
is greater at times of emergent cesarean delivery when compared to elective
cesarean delivery.Limitations of this study include the small number of
study patients with severe HIV disease status as determined byCD4 lymphocyte
counts and viral  load quantifications. Thus, we were not able to demonstrate
the association between post-operative morbidity among HIV-infected women and
the severity of their diseases. Larger study populations are necessary to truly
examine the impact of disease status on postoperative morbidity in HIV-infected
patients.  We also did not evaluate the
use of antiretroviral medications and are unable to comment on any possible
effects that these medications may have had on postoperative morbidity.  This study was also limited due to its
retrospective approach to data collection. A large prospective study will
better evaluate the post-operative morbidities of cesarean delivery in
HIV-infected women.



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