preterm premature rupture of membranes ( pprom ) occurs in approximately 3% 
		 of all pregnancies , accounting for nearly 1/3 of all 
 preterm births [ 15 ] 
 . moreover , pprom is a contributor 
 to perinatal morbidity and mortality  primarily due to its 
 association with delivery remote from term , 
 chorioamnionitis , placental abruption , and umbilical cord 
 compression or prolapse [ 1 , 2 ] 
  management of women with hiv infection who 
 develop pprom poses an obstetric dilemma .
limited data are 
 available to direct optimal management of hiv - positive women who 
 develop pprom .
previous investigations have demonstrated that in 
 term pregnancies complicated by maternal hiv infection , duration 
 of membrane rupture > 4 hours increases the risk of intrapartum 
 vertical transmission [ 1217 ] . by extrapolation 
 of this data
, some authors suggest that women with hiv who undergo 
 pprom should not be managed conservatively [ 1 , 
 1214 ]
. 
 however , in instances near the limits of viability , conservative 
 management of pprom may be justified because of the extremely high 
 risk of mortality and chronic morbidity when immediate delivery is 
 prompted .
we and others   have been 
 unable to identify any published manuscripts to date reporting on 
 conservative management of pprom in the setting of hiv ( medline search 1 
 january 19661 september 2005 : search terms : preterm premature 
 rupture of membranes , human immunodeficiency virus infection , 
 acquired immunodeficiency syndrome ) . given an absolute lack of 
 published reports , we sought to provide an initial report on the 
 management and outcomes of a series of hiv - infected women whose 
 pregnancies were complicated by preterm premature rupture of 
 membranes ( pprom ) .
discussion of management options in each instance , a thorough and complete review of the relative risks of prematurity 
 and pprom remote from term and potential for vertical transmission 
 with prolonged rupture of the membranes was reviewed with the 
 patient , and documented in the patient chart .
these discussions 
 involved obstetrician / gynecologists , maternal - fetal medicine 
 specialists , neonatologists , and/or infectious disease specialists , 
 with language interpreters as indicated . at hennepin county medical center ( hcmc )
, 
 the hiv - infected women were identified through the hcmc hiv database 
 encompassing the interval from 1990 to 2004 , and the 
 electronic medical records ( emrs ) system was reviewed to identify 
 whether they had been seen through the obstetrics and gynecology 
 clinics , high - risk obstetrics clinics , or on labor and delivery . 
 for those with identified encounters , exhaustive review of both 
 the emr and patient chart was undertaken to ascertain whether a 
 pregnancy had occurred , and whether the pregnancy had been 
 complicated by pprom remote from term . at the university of 
 alabama at birmingham ( uab ) , an electronic obstetric database 
 ( obar ) of women who obtained their prenatal care and delivered at 
 uab from 1980 to 2004 was searched .
women with hiv having 
 undergone prom were identified and for those women in whom latency 
 was greater than 24 hours , an exhaustive chart review was 
 performed .
pprom remote from term was defined as preterm , 
 premature rupture of the membranes prior to 32-week gestation 
 confirmed by ferning , pooling , or indigo - carmine amnioinfusion ; 
 dating was by previously published american college of 
 obstetricians and gynecologist ( acog ) criteria and employed last 
 menstrual period with fetal biometry by ultrasonographic 
 determination .
maternal hiv - positive status was defined 
 as documentation of hiv-1 or hiv-2 seroconversion , confirmed 
 by western blot analysis .
aids was defined as an absolute cd4 + , 
 cd3 + lymphocyte count less than 200 10 cells / l . 

infants were considered infected if they were hiv - seropositive , 
 confirmed by western blot at > 18 months of age , had two or more 
 positive pcr tests or viral cultures at any age , had an 
 aids - defining illness , or if they died with an hiv - related 
 condition .
once a pregnancy was identified as having 
 been dually complicated by hiv - positive maternal status 
 and prom remote from term , data was uniformly extracted from the 
 patients chart with respect to maternal characteristics ( age , 
 ethnicity , parity , year of hiv - positive diagnosis , past medical 
 history , polysubstance abuse history , and infectious 
 comorbidities ) , prenatal care ( gestational age and dating 
 criteria , gestational age at initiation of prenatal care , 
 gestational age at initiation of haart / therapy , number of prenatal 
 visits ) , hiv characteristics ( genotype , aids , infectious 
 comorbidities [ gbs , trichomonas , gonorrhea , chlamydia , 
 ppd , hepatitis a , b , or c ] ) , pprom characteristics ( means of 
 confirmation , most recent viral load and cd4 count prior to pprom , 
 antiviral therapy at pprom , gestational age at delivery , latency 
 interval , indication for delivery , clinical or histologic evidence 
 of chorioamnionitis ) , use of antiviral and antimicrobial therapy 
 ( haart / intrapartum azt , duration of use , utilization of 
 antibiotics for the prolongation of latency ) , maternal peripartum 
 complications ( sepsis , chorioamnionitis , endometritis ) , and fetal 
 and infant characteristics ( administration of steroids for the 
 promotion of fetal lung maturity , infant sex , birth weight , 
 apgars , cord gasses , nicu admission and duration of nicu stay , 
 neonatal sepsis , rds , ivh , necrotizing enterocolitis , vertical 
 transmission , other complications or medical morbidities ) . at hcmc ,
the hiv database for women with hiv 
 is supported by infectious disease hiv clinic with irb approval . 

as this represented a case series , no further irb approval was 
 deemed necessary . at uab
patient characteristics ( table 1 ) over the indicated study intervals at hcmc and uab , birmingham , we 
 identified 291 pregnancies having occurred in the cohort of 
 hiv - positive women . of these pregnancies ,
7 ( 2.4% ) developed pprom with subsequent delivery 
 from 25-to 32-week 
 gestation . with the exception of one patient ( patient 1 ) , all 
 women received prenatal care in their first or early midtrimester . 

for those who received adequate prenatal care , medical 
 comorbidities reported reflect those found in the at - large hcmc 
 and uab populations .
hiv and infectious morbidity ( table 2 ) with the exception of two patients ( patients 2 and 6 ) , all 
 women were aware of their diagnosis of hiv prior to the pregnancy . 

note that the diagnosis of hiv seroconversion ( for patient 1 ) 
 occurred in a prior pregnancy , but treatment was never initiated 
 secondary to failed followup ; this was in spite of multiple 
 attempts to encourage compliance with care . 
 
each of the patients who received prenatal care at hcmc was 
 initiated on haart in the early midtrimester ; two of these 
 patients 
  continued a modification of their prepregnancy therapy 
 ( table 2 ) . at uab ,
both pregnancies occurred ( 1993 ) 
 prior to the use of haart in pregnancy .
one woman ( patient 6 ) 
 was part of the pactg 076 trial and was randomized to placebo . 

all patients were screened for viral and bacterial infectious 
 comorbidities on initial presentation ; all were rescreened on 
 admission .
none were hepatitis b surface antigen - positive , one was 
 hepatitis c positive ( patient 7 ) ; one ( patient 3 ) had been 
 previously exposed to hepatitis a but was without active disease . 

three of the 7 patients had trichomonas vaginalis 
 detected and treated , and one woman ( patient 1 ) was positive and 
 treated for trichomonas , c trachomatis , and n 
 gonorrhea at the time of admission .
two women ( patients 3 and 7 ) had a history of tuberculosis , and had previously 
 received therapy accordingly .
pprom and delivery characteristics ( table 3 ) each patient in our series was distinct from the others with 
 respect to gestational age at the time of pprom ; however , the 
 overall profile typifies that seen among hiv - negative women with 
 pprom . in one instance ( patient 2 ) ,
pprom occurred prior to 
 viability and extensive counseling regarding the risks of 
 oligohydramnios and prolonged ruptured membranes was undertaken . 
 the patient elected to pursue expectant management .
with respect to viral load at the time of pprom , one woman 
 ( patient 1 ) was hospitalized for preterm labor when rupture of 
 membranes occurred . with respect to patients 2 and 5 , 
 noncompliance with
however , with inpatient management ( patient 5 ) and 
 frequent outpatient visits ( patient 2 ) , compliance improved and 
 the viral load declined accordingly ( table 3 ) . as 
 per protocol standard at the time of presentation , viral loads 
 were not obtained in the women that delivered at uab . all patients with ongoing pregnancies at hcmc received intravenous 
 azt for a maximum of 48 hours following membrane rupture , with 
 repeat administration of therapy proximal to delivery . during the 
 same interval ,
the single exception to optimal 
 utilization of intrapartum azt use was patient 3 , as she had 
 experienced a prior episode of neutropenic sepsis with ards . at 
 uab ,
intrapartum azt was not administered to one woman ( patient 6 ) as per study ( pactg 076 ) protocol following randomization 
 to placebo . in another patient , intravenous azt
was administered 
 for 60 hours during her prolonged latent phase ( from the time 
 of admission to the time of delivery ) .
the mean latency in this cohort was 17.1 days with a median of 5 days ; one woman ( patient 2 ) 
 had a latency of 92 days . 

indications for delivery typified that of pregnancies complicated 
 by pprom , and mode of delivery was determined by obstetrical 
 indications ( table 3 ) .
maternal complications ( table 3 ) clinical or 
 histologic evidence of chorioamnionitis was prevalent ; 
 endometritis ensued in four cases .
there was one instance of 
 maternal sepsis with positive blood cultures for 
 peptostreptococcus .
otherwise , the duration of 
 postdelivery hospitalization mirrored that of the general 
 obstetric population at the respective institutions .
infant sequelae and complications ( table 4 ) neonatal outcomes of the pregnancies in our series are shown in 
 table 4 .
vertical hiv transmission was noted in 2 of the possible 6 cases ( 33% ) . 
 in the two instances of vertical transmission ,
one woman and infant pair received no 
 antiretroviral therapy as per study ( pactg 076 ) protocol . in the 
 second instance , azt was the only antiretroviral employed and 
 viral loads were not used to guide delivery practice .
all infants 
 ( except for patient 6 ( pactg 076 protocol ) ) received 
 antiretroviral therapy in the neonatal period as per standard of 
 care . of the cases without vertical transmission in our series
, 
 all women received haart at the time of pprom with cesarean 
 delivery for those with a viral load > 1000 copies / ml .
in our series , there were no instances of vertical transmission in 
 women with pprom who were receiving multidrug therapy or haart 
 despite prolonged intervals of rupture of membranes .
the only two 
 cases of vertical transmission observed were in one woman who did 
 not receive antepartum or intrapartum antiretroviral therapy , and 
 in another who received only azt in the antepartum period .
our 
 observations suggest that in the era of haart , one might consider 
 whether or not immediate delivery should be undertaken in 
 pregnancies complicated by pprom at an early gestational age . 

alternatively , in pregnancies that may lend themselves to 
 expectant management , such a strategy should be entertained . in pregnancies complicated by maternal hiv infection ,
duration of 
 rupture of membranes > 4 hours , in term pregnancies 
 appear to increase the risk of intrapartum vertical 
 transmission [ 1217 ] . 
 in one study , 
 prolonged rupture of membranes in term (
> 37 weeks ) relative to 
 preterm ( < 37 weeks ) was assessed .
the authors found a 3.8-fold 
 rr ( 95% ci 1.9 , 7.8 ) increase in intrapartum hiv 
 transmission when comparing preterm to term infants whose 
 membranes had been ruptured > 4 hours .
these authors attempted to 
 delineate whether vertical transmission occurred in the 
 intrauterine or intrapartum period and came to the 
 conclusion that  preterm infants are at increased risk of 
 acquiring infection at the time of delivery , 
however , transmission risk was not stratified by use of 
 antiretroviral therapy , gestational age , nor mode of delivery 
 . as with this study ,
other studies [ 1217 ] exploring the relationship of duration of membrane 
 rupture and perinatal hiv transmission have failed to account for the use 
 of haart and viral load at the time of delivery .
one recent analysis   investigated the risk of perinatal 
 hiv transmission in women on combination antiretroviral therapy 
 with viral loads < 1000 copies / ml and membrane rupture > 4 
 hours .
interestingly , monotherapy ( or 6.3 , ci 2.416.6 ) or lack of antiretroviral therapy ( or 17.4 
 ci 6.745.5 ) and viral load > 1000 copies / ml ( or 9.9 , ci 1.284.5 ) were independently associated with neonatal 
 infection .
our case series suggests that this relationship between 
 combination antiretroviral therapy and reduction in the rate of 
 vertical transmission may apply to pregnancies complicated by 
 prolonged premature preterm rupture of membranes and hiv .
we recognize that the primary limitation of this study is its 
 limited sample size and its heterogeneous population .
our series 
 does not claim to provide any statistical risk assessment for 
 counseling patients on the relative merits or risks of 
 transmission in the setting of pprom remote from term .
rather , it 
 is our hope that this novel series will provide an impetus to 
 further reports and larger multi - institutional investigations to 
 address this important clinical issue .
we report a novel case series describing management and outcomes 
 in human immunodeficiency virus - infected women who developed 
 preterm premature rupture of membranes remote from term .
pnc : 
 prenatal care ; ards : adult respiratory distress syndrome ; azt : 
 zidovudine ; aids : acquired immunodeficiency syndrome ; n / a : data 
 not available . hiv and infectious morbidity . hiv : human immunodeficiency 
 virus ; aids : acquired immunodeficiency syndrome ; haart : highly 
 active antiretroviral therapy ; azt : zidovudine ; inh : isoniazide ; 
 pactg : the pediatric aids clinical trials group ; tb : tuberculosis ; 
 s / p : status - post .
pprom : 
 preterm premature rupture of membranes ; haart : highly active 
 antiretroviral therapy ; azt : zidovudine ; c / s : cesarean delivery ; 
 iufd : intrauterine fetal demise ; nsvd : spontaneous vaginal 
 delivery ; n / a : data not available .
nicu : neonatal intensive 
 care unit ; rds : respiratory distress syndrome ; ivh : 
 intraventricular hemorrhage ; nec : necrotizing enterocolitis ; iufd : 
 intrauterine fetal demise ; vsd : ventriculoseptal 
 defect .
 objective . to evaluate the management and outcomes of a 
 series of human immunodeficiency virus-(hiv- ) infected women 
 whose 
 pregnancies were complicated by preterm premature rupture of 
 membranes ( pprom ) . study design . 
 we conducted a 
 retrospective chart review of all women with confirmed hiv 
 infection who had a pregnancy complicated by pprom remote from 
 term . 
 pprom remote from term was defined as rupture of membranes 
 prior to 32-week gestation . 
 collective cases from two centers 
 ( hennepin county medical center and the university of alabama at 
 birmingham ) were reviewed and data on management and outcomes were 
 abstracted . results . 
 of the hiv - positive women , we 
 identified 291 pregnancies having occurred in the study interval 
 from two institutions . 
 of these pregnancies , 7 ( 2.4% ) 
 developed pprom remote from term with subsequent delivery from 25- to 32-week gestation . 
 vertical hiv transmission was noted 
 in 2 of 6 children whose long - term followup status was confirmed 
 ( 33% ) of these cases . 
 however , both of these cases occurred 
 in women with either no antepartum / intrapartum antiviral therapy 
 or where only zidovudine monotherapy was used . 
 importantly , in 
 spite of expectant management , no cases of vertical hiv 
 transmission occurred in women who were receiving either multidrug 
 or highly active antiviral therapy ( haart ) at the time of pprom 
 and who had a cesarean delivery in cases where the predelivery 
 viral load > 1000 copies / ml . conclusion . 
 our limited 
 observations raise the question as to whether in the current era 
 of multidrug therapy immediate delivery should be undertaken in 
 hiv+ pregnancies complicated by pprom at an early gestational age . 
 
 this case series further suggests that in those pregnancies that 
 lend themselves to expectant management , such a strategy may be 
 considered appropriate . 
INTRODUCTION
MATERIALS AND METHODS
RESULTS
COMMENTS
CONDENSATION
Figures and Tables