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Journal of Obstetrics and Gynaecology, 2015; Early Online: 1–6

© 2015 Informa UK, Ltd.

ISSN 0144-3615 print/ISSN 1364-6893 online
DOI: 10.3109/01443615.2014.990432


Conservative management of preterm premature rupture of membranes

beyond 32 weeks’ gestation: Is it worthwhile?
Z. Tsafrir1, G. Margolis1, Y. Cohen1, A. Cohen1, I. Laskov1, I. Levin1, D. Mandel2 & A. Many1
1The Department of Gynecology and 2Neonatal Intensive Care Unit, Lis Maternity Hospital, Tel-Aviv Sourasky Medical Center, Sackler Faculty

of Medicine, Tel-Aviv University, Tel Aviv, Israel

necrotising enterocolitis (NEC) and neonatal sepsis (Egarter et al.

We aimed to investigate whether conservative management
1996; Lewis et al. 1996; Pattinson et al. 1999; Kenyon et al. 2003).
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of preterm premature rupture of membranes (PPROM) at

In addition, prophylactic antibiotic treatment assists in reducing
32–34 weeks’ gestation improves outcome. In this retrospective
the likelihood of chorioamnionitis and delays delivery, thereby
analysis of singleton pregnancies, the study group included
allowing sufficient time for the administration of prophylactic
patients with PPROM at 28–34 weeks’ gestation and the control
prenatal corticosteroids (Mercer et al. 1997; Kenyon et al. 2001;
group included patients presented with spontaneous preterm
RCOG 2006). However, an extended latency period may increase
delivery at 28–34 weeks’ gestation. Both groups were subdivided
the risk of chorioamnionitis, thereby exposing the foetus to an
according to gestational age – early (28–31 weeks’ gestation)
unfavourable intrauterine environment, which is associated with
versus late (32–34 weeks’ gestation). Adverse neonatal outcome
adverse neonatal outcomes, including cerebral palsy, lung injury,
included neonatal death, intraventricular haemorrhage grade
NEC and early neonatal sepsis. Other complications associated
3/4, respiratory distress syndrome, periventricular leucomalacia
with conservative management include cord compression due to
and neonatal sepsis. The study and control groups included
oligohydramnios and umbilical cord prolapse, especially in cases
For personal use only.

94 and 86 women, respectively. The study group had a lower

of malpresentation.
incidence of adverse neonatal outcome at the earlier weeks
There is a consensus on the need for expeditious delivery in the
(28–31), compared with the control group at the same
following scenarios, regardless of gestational age: (1) overt chorio-
gestational age. In contrast, at 32–34 weeks’ gestation no
amnionitis, (2) abruptio placenta, (3) foetal distress and (4) advanced
difference in the risk for adverse neonatal outcome was
labour. In the event of foetal malpresentation and significant cervical
noticed. Additionally, within the study group, chorioamnionitis
dilatation, it may be justified to operate without delay. Furthermore,
rate was significantly higher among those who delivered at
induction of labour is the accepted policy when PPROM occurs at
32–34 weeks’ gestation (p ⬍ 0.01). No advantage for
or beyond 34 weeks’ gestation, or in the cases of PPROM which had
conservative management of PPROM was demonstrated
been managed expectantly and reached 34 weeks’ gestation (ACOG
beyond 31 weeks’ gestation. Moreover, conservative
2007). The American Congress of Obstetricians and Gynecologists
management of PPROM at 32–34 weeks’ gestation may
(ACOG) recommends conservative management with the admin-
expose both mother and neonate to infectious morbidity.
istration of glucocorticoids and antibiotics up to 33 weeks’ gestation
Keywords: Conservative management, chorioamnionitis, outcome, (ACOG 2007). However, the Royal College of Obstetricians and
preterm premature rupture of membranes Gynecologists (RCOG) states that delivery should be considered at
34 weeks’ gestation (RCOG 2006).
There is also wide agreement that in the absence of any of the
Introduction indications mentioned above, women who present with PPROM
Preterm premature rupture of membranes (PPROM) accounts remote from term (i.e. ⬍ 32 weeks’ gestation) should be treated
for nearly 3% of all pregnancies and is a leading cause of expectantly. In cases of PPROM at 32–34 weeks’ gestation, how-
maternal and perinatal morbidity and mortality (Mercer 2003; ever, the optimal management is controversial. We performed this
ACOG 2007). There is an inverse correlation between the fre- retrospective analysis in order to determine whether expectant
quency and severity of neonatal complications after PROM and management in PPROM at 32–34 weeks’ gestation is beneficial.
the gestational age at membrane rupture and at delivery (Locatelli
et al. 2005). The appropriate management in the event of PPROM
is controversial (Ramsey et al. 2004). Expectant management Materials and methods
is justified in order to decrease gestational age-related morbid- This retrospective cohort analysis was conducted on all
ity associated with prematurity. Accumulated experience in the singleton pregnancies that were delivered at 280/7–346/7 weeks’
last decade established the benefit of administering prophylactic gestation between 2004 and 2011 in a single tertiary centre.
glucocorticoids and antibiotics before 32 weeks’ gestation in pre- The study group was comprised of women who presented with
venting neonatal morbidity and mortality, especially respiratory PPROM. The control group included randomly selected women
distress syndrome (RDS), intraventricular haemorrhage (IVH), who presented with spontaneous preterm labour (SPTL) and

Correspondence: Ziv Tsafrir, MD, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, 6 Weizman Street, Tel Aviv 64239, Israel. Tel: ⫹ 972-3-6925604.
Fax: ⫹ 972-3-6925687 and Current address: 7632 Goshen Dr. West Bloomfield, Michigan 48322, USA. Tel: ⫹ 1-248-859-5255, 1-248826-3782, 1-313-673-
4757. Fax: ⫹ 1-248-325-0094. E-mail:
2 Z. Tsafrir et al.

intact membranes, during the same study period. Both groups (PDA), bilirubin and haematocrit levels, phototherapy treat-
were divided according to gestational age at delivery: early ment, erythropoietin treatment, documented hypoglycaemia or
(280/7–316/7) and late (320/7–336/7). Patients who presented hyponatremia, and administration of surfactants.
with PPROM or SPTL and gave birth before the completion of
34 weeks’ gestation (i.e. ⬍ 35 weeks’ gestation) were included in Statistical analysis
the ‘late’ group as well. We excluded all pregnancies with known According to our calculation with the implementation of Z-test,
foetal malformations, multiple foetuses, stillbirths, placenta pre- a sample size of 90 patients in each studied group could reveal
via, women who presented with abruptio placenta and cases in a decrease of at least 25% in the incidence of composite adverse
which a decision to deliver was made due to other maternal or neonatal outcome in the study group compared with that in the
foetal indications. Women who delivered within 24 h of PPROM control group, with a power of 80% at the 0.05 significance level.
were also excluded from the study group. This study was approved This assumption was based upon accepted differences in the
by the Institutional Review Board. literature regarding the rate of RDS, IVH stage 3/4, PVL, sepsis,
PPROM was defined as spontaneous rupture of membranes and neonatal death between newborns before 32 weeks’ gestation
(ROM) occurring before the onset of active labour and at and those at 32–34 weeks’ gestation (Mercer, 2003; Hartling et al.
⬍ 340/7 weeks’ gestation. ROM was diagnosed by the observation 2006; RCOG, 2006). Data were analysed with the Student’s t-test,
of persistent vaginal pooling on sterile speculum examination. the χ2 test and the Fisher’s exact test as appropriate. A multivari-
Gestational age was determined by the last menstrual period, able logistic regression with backward elimination was performed
and confirmed by first-trimester ultrasound. The latency period to examine the effect of possible confounding variables that were
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was defined as ‘the time interval between ROM and time of considered risk factors for the composite neonatal outcome. Odds
delivery’. Clinical chorioamnionitis was defined as ‘the pres- ratio (OR) and their 95% confidence intervals (CIs) were com-
ence of uterine tenderness and/or foul-smelling amniotic fluid, puted. Probability values of ⬍ 0.05 for all two-tailed tests were
maternal fever (⬎ 38.0°C), leucocytosis or foetal tachycardia’. considered significant.
All women who presented with PPROM at ⬍ 340/7 weeks’ ges-
tation were managed by a standardised protocol as follows: (1)
inpatient management after excluding cases of active labour, cho- Results
rioamnionitis, placental abruption or foetal compromise; (2) intra- During 2004–2011, we had 80,384 deliveries in our medical cen-
muscular administration of betamethasone (12 mg, 2 doses 12 h tre. There were 1262 preterm births at 28–34 weeks’ gestation.
apart) and prophylactic antibiotics (ampicillin and azithromycin) After applying the above-mentioned exclusion criteria, we had
based on the ACOG and RCOG guidelines (ACOG, 2007; RCOG, 238 cases of PPROM, of which 94 singleton pregnancies were
For personal use only.

2006); (3) urine culture upon admission; and (4) monitoring of mater- eligible for study entry, that is the women presented with PPROM
nal and foetal status for signs of chorioamnionitis, labour and/or and gave birth after more than 24 h from ROM. In addition, we
foetal compromise. The routine follow-up included daily mea- had 337 cases of SPTL. The control group of 86 women was ran-
surement of vital signs, examination for uterine tenderness, non- domly selected within the same time period. After stratification
stress test three times daily, complete blood count every other day, by gestational age at delivery, there were 43 women in the study
biophysical profile twice a week and estimation of foetal weight group who delivered between 280 and 316/7 weeks’ gestation (the
every 2 weeks. Vaginal examination was avoided unless the patient early PPROM subgroup), and 51 women who delivered between
was symptomatic or complained of contractions. 32 and 34 weeks’ gestation (the late PPROM subgroup). The con-
Indications for rejecting expectant management were cho- trol group consisted of 37 and 49 women in the early and late
rioamnionitis, abruption placenta, foetal compromise and active SPTL subgroups, respectively. Demographic and obstetric details
labour. Tocolysis was avoided for women who presented with of all four subgroups are summarised in Table I.
PPROM. Women who presented with SPTL were given betame- The late PPROM subgroup had more events of urinary tract
thasone at the time of admission to the emergency room. All the infection (UTI) compared with the late PTL subgroup (9 vs. 1;
women in active labour were treated using prophylactic antibi- p ⬍ 0.01). Cerclage in the current pregnancy or a history of cervi-
otics intrapartum (intravenous penicillin 5 million U, followed cal procedures was present in 7/43 of early PPROM cases com-
by 2.5 million U every 4 h) to prevent vertical transmission of pared with 0/37 early SPTL cases (p ⬍ 0.01).
group B streptococci, regardless of earlier treatments. Induction
of labour, when indicated, was performed by oxytocin. Neonatal outcome
Data for this study were retrieved from our computerised The rate of composite adverse neonatal outcome was significantly
obstetrics database as well as from neonatal intensive care unit lower in the early PPROM subgroup than that of the early SPTL
(NICU) records. Maternal information included demographics, subgroup but not between the late PPROM and SPTL subgroups
age, height, weight and calculated body mass index, smoking, (Table II). In order to examine whether the better neonatal
alcohol use and medical and obstetrical history. Obstetrical infor- outcome in PPROM events at 28–31 weeks’ gestation could be
mation included current pregnancy follow-up, latency period, attributed to expectant management, we used linear regression
mode of delivery and complications. Clinical chorioamnionitis and included potential confounders that might affect neonatal
was confirmed by histopathological examination when available. outcome, i.e. maternal age, parity, caesarean section/operative
Primary adverse neonatal outcomes included IVH, sepsis, RDS, delivery, chorioamnionitis and birth weight. The expectant man-
NEC, retinopathy of prematurity, periventricular leucomalacia agement of PPROM at 28–31 weeks’ gestation was associated with
(PVL) and neonatal death. The composite adverse neonatal out- less neonatal morbidity than preterm deliveries at 28–31 weeks’
come was defined as ‘the presence of at least one of the followings: gestation, even after adjusting for the variables mentioned above
RDS, IVH stage ¾, PVL, sepsis and neonatal death’. Secondary (OR: 0.34; 95% CI: 0.13–0.89).
neonatal outcomes included number of days in the NICU, birth Analysis of secondary adverse neonatal outcome (Table III)
weight, Apgar score, intubation/mechanical ventilation in the revealed that more cases of PDA occurred in the early SPTL
delivery room, hypotension, inotropic or crystalloids support, subgroup compared with those in the early PPROM subgroup
administration of indomethacin for patent ductus arteriosus (13 vs. 5; p ⫽ 0.013). In addition, fewer premature newborns in
Conservative management of PPROM 3
Table I. Demographic and obstetric characteristics of pregnancies with PPROM and SPTL.

Early gestational age at labour Late gestational age at labour

(28–31 weeks) (32–34 weeks)


Characteristics (n ⫽ 43) (n ⫽ 37) p value (n ⫽ 51) (n ⫽ 49) p

Maternal age (years) 32.7 ⫾ 6.1 31.6 ⫾ 9.0 0.14 31.6 ⫾ 5.8 31.1 ⫾ 5.1 0.65
Body mass index (kg/m2) 20.5 ⫾ 3.5 20.4 ⫾ 3.5 0.96 21.0 ⫾ 4.6 21.1 ⫾ 3.8 0.89
Smoking rate 2 (4.6) 2 (5.4) 0.87 7 (13.7) 6 (12.2) 0.41
Pre-gestational diabetes 0 0 N/A 0 1 (2) N/A
History of abdominal surgery 4 (9.3) 1 (2.7) 0.21 5 (8.7) 4 (8.1) 0.39
History of caesarean section 3 (6.9) 3 (8.1) 0.92 5 (9.8) 5 (10.2) 0.97
Nulliparous 15 (34.8) 21 (56.7) 0.04 21 (41.1) 16 (32.6) 0.6
Recurrent pregnancy loss (⬎ 2 miscarriages) 10 (23.2) 3 (8.1) 0.07 14 (27.4) 10 (20.4) 0.48
Previous SPTL 2 (4.6) 4 (10.8) 0.31 8 (15.6) 11 (22.4) 0.2
Assisted reproductive technique 7 (16.3) 1 (2.7) 0.06 5 (9.8) 5 (10.2) 0.97
Gestational diabetes 2 (4.6) 2 (5.4) 0.87 3 (5.8) 7 (14.3) 0.08
UTI 3 (6.9) 2 (4.6) 0.77 9 (17.6) 1 (2) ⬍ 0.01
Cerclage in current pregnancy/history of cervical procedure 7 (16.2) 0 (0) ⬍ 0.01 3 (5.8) 5 (10.2) 0.21
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Antepartum vaginal bleeding 5 (11.3) 3 (8.1) 0.6 5 (9.8) 3 (6.1) 0.25

Data presented as number (%) or mean ⫾ standard deviation (SD).

N/A, not applicable.

the early PPROM subgroup needed fluids or inotropic support neonates of both groups of women. These results were repeated
and their mean haematocrit level was higher compared with the even after applying multivariate analysis, which included latency
newborns in the early SPTL subgroup, although these differences period, maternal age, birth weight, UTI during pregnancy, cur-
did not reach a level of significance. rent cerclage or history of cervical procedures, and chorioamni-
onitis. We next evaluated the effect of the duration of the latency
Maternal outcome period on the rate of chorioamnionitis in the PPROM group
For personal use only.

Women who presented with PPROM at 32–34 weeks’ gesta- and found no significant difference between the women with
tion suffered from a higher rate of clinical and histological short or long latency periods at any gestational age. The rate of
chorioamnionitis, underwent more operative deliveries/cae- neonatal sepsis among neonates who were born at 32–34 weeks’
sarean sections and had prolonged length of stay in hospital gestation after a prolonged latency period, however, was higher
compared with the control women. These differences also compared with that of neonates who were born after a short
applied to the earlier PPROM subgroup (Table IV). There were latency period (15.3% vs. 0%; p ⫽ 0.05). This difference was not
more cases of chorioamnionitis in the PPROM group at 28–31 observed in PPROM cases at 28–31 weeks’ gestation.
weeks’ gestation compared with 32–34 weeks’ gestation (15 vs. Finally, we performed a multivariate regression analysis
9; p ⬍ 0.05). in order to determine which risk factors for PPROM were
independently or directly associated with the composite
Effect of a latency period adverse neonatal outcome. The results showed that gestational
In order to examine the influence of a latency period on adverse age at the time of membrane rupture correlated to adverse
neonatal outcome of the PPROM women, we divided these neonatal outcome, even after adjustment for confounding fac-
patients into cases with a prolonged latency period (i.e. ⬎ 7 tors, such as maternal age, history of vaginal bleeding, cho-
days) and cases with a short latency period (i.e. ⱕ 7 days). There rioamnionitis, prolonged latency period, nulliparity and the
was no significant difference in adverse outcome between the newborn’s gender.

Table II. Primary adverse neonatal outcome in PPROM and SPTL Groups.

Early gestational age at labour Late gestational age at labour

(28–31 weeks) (32–34 weeks)

Early PPROM Early PTL Late PPROM Late SPTL

Outcome (n ⫽ 43) (n ⫽ 37) p (n ⫽ 51) (n ⫽ 49) p

Composite neonatal outcome¶ 17 (39.5) 24 (64.9) 0.02 9 (17.6) 11 (22.4) 0.28

Neonatal death 1 (2.3) 1 (2.7) 0.91 0 0 N\A
IVH (grade 3–4) 1 (2.3) 2(5.4) 0.48 0 0 N\A
Neonatal sepsis 6 (13.9) 5 (13.5) 0.95 2 (3.9) 0 0.48
RDS 16 (37.2) 21 (56.7) 0.11 8 (15.6) 11 (22.4) 0.19
NEC 4 (9.2) 2 (5.4) 0.5 2 (3.9) 1 (2.0) 0.29
PVL 0 3 (8.1) 0.09 0 0 N/A
ROP 6 (13.9) 2 (5.4) 0.19 0 0 N/A

Data presented as number (%).

RDS, respiratory distress syndrome; IVH, intraventricular haemorrhage; NEC, necrotising enterocolitis; PVL, periventricular
leucomalacia; ROP, retinopathy of prematurity; N/A, not applicable.
¶Defined in the ‘Materials and methods’ section
4 Z. Tsafrir et al.
Table III. Secondary adverse neonatal outcome in PPROM and SPTL groups.

Early gestational age at labour Late gestational age at labour

(28–31 weeks) (32–34 weeks)

Early PPROM Early PTL Late PPROM Late SPTL

Outcome (n ⫽ 43) (n ⫽ 37) p (n ⫽ 51) (n ⫽ 49) p

Days at the NICU 40.9 ⫾ 12.5 44.9 ⫾ 15 0.84 18.9 ⫾ 8.3 17.2 ⫾ 7.5 0.88
Birth weight(g) 1477 ⫾ 285 1503 ⫾ 266 0.68 2018 ⫾ 234 2148 ⫾ 305 0.73
Apgar score ⬍ 7 at 1 min 9 (20.9) 7 (18.9) 1 6 (11.7) 6 (12.2) 1
Apgar score ⬍ 7 at 5 min 2 (4.6) 1 (2.7) 1 1 (1.9) 3 (6.1) 0.35
Hypotension at admission to NICU 3 (6.9) 6 (16.2) 0.2 2 (3.9) 3 (6.1) 0.3
Fluids/inotropic agents treatment 4 (9.3) 9 (24.3) 0.08 3 (5.8) 3 (6.1) 0.48
PDA 5 (11.6) 13 (35.1) 0.014 1 (1.9) 2 (4.0) 0.27
Indomethacin treatment 4 (9.3) 9 (24.3) 0.08 0 0 N/A
Jaundice requiring phototherapy 32 (74.4) 24 (64.8) 0.36 21 (41.2) 17 (34.6) 0.25
Haematocrit upon discharge 34.4 ⫾ 4.6 32.4 ⫾ 5.3 0.07 44.1 ⫾ 7.6 42.6 ⫾ 10.6 0.45
Erythropoietin treatment 13 (30) 11(29) 0.96 0 0 N/A
Hypoglycaemia 3 (6.9) 2 (5.4) 0.77 6 (11.8) 4 (8.1) 0.27
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Hyponatremia 4 (9.3) 3 (8.1) 0.85 0 0 N/A

Data presented as number (%) or mean ⫾ SD.

NICU, neonatal intensive care unit.

Discussion management (Van Der Ham et al. 2012). Mercer et al.’s ran-
The results of our analysis demonstrate that expectant manage- domised controlled study demonstrated the importance of anti-
ment of women presenting with PPROM at 28–31 weeks’ gesta- biotic therapy in the event of PPROM occurring up to 32 weeks’
tion is associated with lower rates of adverse neonatal outcome gestation (Mercer et al. 1997). The ACOG recommends conserva-
compared with cases of SPTL at the same gestational age. How- tive management with the administration of glucocorticoids and
ever, we did not detect any benefit for conservative management antibiotics up to 33 weeks’ gestation (ACOG 2007). However,
For personal use only.

in the event of PPROM occurrence at 32–34 weeks’ gestation. The the RCOG states that delivery should be considered at 34 weeks’
most appropriate model to evaluate the benefit of expectant man- gestation, and that women should be informed of the increased
agement of a PPROM event is a prospective clinical trial in which risk of chorioamnionitis and the decreased risk of respiratory
obstetrical and neonatal outcomes of PPROM cases managed problems in the neonate (RCOG 2006).
expectantly are compared with PPROM cases who were actively An alternative model is to compare the obstetrical and neo-
delivered. Hartling et al.’s meta-analysis evaluated four randomised natal outcomes of PPROM versus SPTL. Only a few such studies
controlled trials that were relevant to this issue. These authors were identified in our literature search. Sims et al. retrospectively
concluded that while intentional delivery may be more favourable compared a PPROM group of 99 neonates and an SPTL group of
than expectant management for some maternal outcomes, there 267 neonates (at 24–34 weeks’ gestation). Similar to our study
is insufficient evidence to suggest that either strategy is beneficial findings, women who presented with PPROM and delivered
or harmful for the baby (Spinnato et al. 1987; Cox and Leveno within 24 h were excluded, and steroid and antibiotics were
1995; Mercer et al. 1996; Naef et al. 1998; Hartling et al. 2006). administered to all PPROM patients. Their results showed that
Since none of those trials included glucocorticoids or systematic neonates in the PPROM group had a lower incidence of RDS
antibiotic treatment as part of the management, their relevance to (Sims et al. 2002). Sciscione et al. analysed the outcome of neo-
the contemporary clinical context is called into doubt. nates with very low birth weight (⬍ 1500 g) who were delivered
Van Der Ham et al. randomised women who presented with due to SPTL versus similar infants who were delivered due to
PPROM between 340 and 370 weeks’ gestation to either induc- PPROM. Their cohort is comparable to the early subgroups in
tion of labour or expectant management. Patients in both groups our study. These authors concluded that the neonates who were
received antibiotics. The authors found that induction of labour delivered as a result of PPROM had a higher survival rate than
did not improve pregnancy outcomes compared with expectant those who were delivered after SPTL (Sciscione et al. 2008).

Table IV. Maternal outcome in PPROM and SPTL Groups.

Early gestational age at labour Late gestational age at labour

(28–31 weeks) (32–34 weeks)

Early PPROM Early SPTL Late PPROM Late PTL

Outcome (n ⫽ 43) (n ⫽ 37) p (n ⫽ 51) (n ⫽ 49) p

Caesarean/instrumental deliveries 17 (39.5) 7 (18.9) 0.05 18 (35.2) 4 (8.1) ⬍ 0.01

Chorioamnionitis 15 (34.8) 8 (21.6) 0.19 9 (17.6) 1 (2) ⬍ 0.01
White blood count max (mm3) 17.3 ⫾ 5.1 14.3 ⫾ 3.8 ⬍ 0.01 16.2 ⫾ 4.2 13.1 ⫾ 3.3 0.06
Body temperature (Co) 37.3 ⫾ 0.6 37.1 ⫾ 0.5 0.08 37.1 ⫾ 0.3 36.8 ⫾ 0.4 ⬍ 0.01
LOS postpartum (days) 3.1 ⫾ 1.2 2.5 ⫾ 0.9 0.049 2.9 ⫾ 1.4 2.2 ⫾ 0.5 ⬍ 0.01

Data presented as number (%) or mean ⫾ SD.

LOS, length of stay; N/A, not applicable.
Conservative management of PPROM 5

We observed that the group of women who presented with Acknowledgments

PPROM at 32–34 weeks’ gestation (the late subgroup) had a sig-
We thank Esther Eshkol, the institutional medical and scientific
nificantly higher rate of chorioamnionitis and operative delivery
or caesarean section, as well as prolonged length of post-delivery
stay in hospital compared with the late SPTL subgroup. Tanir Declaration of interest: The authors report no conflicts of
et al. also observed that histological chorioamnionitis was more interest. The authors alone are responsible for the content and
common among PPROM cases compared with that among SPTL writing of the paper.
cases, but they did not stratify the outcome according to gesta-
tional week (Tanir et al. 2003).
We observed an inverse correlation between gestational age at References
PPROM and the probability of chorioamnionitis, in accordance American Congress of Obstetricians and Gynecologists: Premature rupture
with other reports (Ramsey et al. 2005; Aziz et al. 2008; Test et al. of membranes. 2007. ACOG Practice Bulletin No. 80. American Col-
lege of Obstetrics and Gynecologists. Obstetrics and Gynecology 109:
2011). We did not find any link between the length of latency 1007–1019.
period and the rate of chorioamnionitis in the PPROM group: Aziz N, Cheng YW, Caughey AB. 2008. Factors and outcomes associated with
this is in agreement with Aziz et al., but not with Test et al. and longer latency in premature rupture of membranes. Journal of Maternal-
Ramsey et al., who demonstrated opposite correlations (Ramsey Fetal & Neonatal Medicine 21:821–825.
Cox SM, Leveno KJ. 1995. Intentional delivery versus expectant management
et al. 2005; Aziz et al. 2008; Test et al. 2011). with preterm ruptured membranes at 30–34 weeks’ gestation. Obstetrics
We then scrutinised the effect of a latency period on adverse and Gynecology ;86:875–879.
J Obstet Gynaecol Downloaded from by Nyu Medical Center on 04/28/15

neonatal outcome and found that a prolonged latency period (i.e. Egarter C, Leitich H, Karas H, Weiser F, Husselein P, Kaider A et al.
⬎ 7 days) was not associated with improved neonatal outcome. 1996. Antibiotic treatment in premature rupture of membranes and
Moreover, neonates of women in the PPROM group who had an neonatal morbidity: a meta-analysis. American Journal of Obstetrics and
Gynecology 174:589–597.
extended latency period at 32–34 weeks’ gestation suffered from Hartling L, Chari R, Friesen C, Vandermeer B, Masmonteil TL. 2006. A sys-
higher rates of early neonatal sepsis. tematic review of intentional delivery in women with preterm prelabor
Our results demonstrate that the most important factor influ- rupture of membranes. Journal of Maternal-Fetal Neonatal Medicine
encing neonatal outcome is gestational age at the time of ROM. 19:177–187.
Kenyon S, Boulvain M, Neilson J. 2003. Antibiotics for preterm rupture
In a prospective study of PPROM cases at 24–34 weeks’ gestation, of membranes. Cochrane Database of Systematic Reviews Issue 2. Art
Pasquier et al. did not detect any association between a latency No.:CD001058. DOI:10. 1002/14651858.CD001058.
period and neonatal outcomes. Those authors also concluded that Kenyon SL, Taylor DJ, Tarnow-Mordi W. 2001. Broad spectrum antibiotics
the risk of adverse neonatal outcome is inversely related to gesta- for preterm, pre-labor rupture of fetal membranes: the ORACLE I ran-
For personal use only.

tional age at PPROM (Pasquier et al. 2009). Locatelli et al. found domized trial. ORACLE Collaborative Group. Lancet 357:979–988.
Lewis DF, Brody K, Edwards MS, Brouillette RM, Burlison S, London SN.
that gestational age at PPROM was independently predictive of 1996. Preterm premature ruptured ruptured membranes: a randomized
white matter damage (Locatelli et al. 2005). trial of steroids after treatment with antibiotics. Obstetrics and Gynecol-
The practitioner who advocates expectant management needs ogy 88:801–805.
to find a balance between two opposing processes: as the period of Locatelli A, Ghidini A, Paterlini G, Patane L, Doria V, Zorloni C et al. 2005.
Gestational age at preterm premature rupture of membranes: a risk factor
latency is prolonged, the rate of adverse neonatal outcome associ- for neonatal white matter damage. American Journal of Obstetrics and
ated with prematurity decreases, but the risk of chorioamnionitis Gynecology 193:947–951.
and related neonatal complications increases. We strived to iden- Mercer BM. 2003. Preterm premature rupture of the membranes. Obstetrics
tify the definitive point at which expectant management might and Gynecology 101:178–193.
be counterproductive. According to our observations, expectant Mercer BM, Crocker LG, Boe NM, Sibai BM. 1996. Induction versus expect-
ant management in premature rupture of the membranes with mature
management of a woman with PPROM at 32–34 weeks’ gestation amniotic fluid at 32–36 weeks: a randomized trial. American Journal of
is not associated with improved neonatal outcome. Furthermore, Obstetrics and Gynecology 169:775–778
we witnessed a higher rate of chorioamnionitis and neonatal sep- Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF,
sis in combination with a prolonged latency period among those Ramsey RD et al. 1997. Antibiotic therapy for reduction of infant
morbidity after preterm premature rupture of the membranes. A ran-
women. domized controlled trial. National Institute of Child Health and Human
We are aware of several possible limitations of this study. It Development Maternal-Fetal Medicine Units Network. JAMA 278:
has been claimed that SPTL and PPROM are associated with dif- 989–995.
ferent pathophysiological mechanisms, whereupon a comparison Naef RW, Allbert JR, Ross EL, Weber BH, Martin RW, Morrison JC. 1998.
of neonatal outcome between these two clinical entities may be Premature rupture of membranes at 34 to 37 weeks’ gestation: aggressive
versus conservative management. American Journal of Obstetrics and
open to question. Being limited as we were by the nature of a Gynecology 178:126–130.
retrospective design, we thought that a study group comprised Pasquier JC, Picaud JC, Rabilloud M, Claris O, Ecochard R, Moret S et al.
of SPTL cases will best reflect an alternative management, i.e. 2009. Neonatal outcomes after elective delivery management of preterm
expeditious delivery. An additional weakness of this study is the premature rupture of the membranes before 34 weeks’ gestation (DOMI-
NOS study). European Journal of Obstetrics, Gynecology, and Reproduc-
lack of follow-up, thus precluding knowledge of the long-term tive Biology 143:18–23.
outcome of these premature newborns, especially with regard to Pattinson RC, Makin JD, Funk M, Delrot SD, Macdonald AP, Norman K
their neurological development. et al. 1999. The use of dexamethasone in women with preterm premature
In summary, our findings demonstrate that expectant man- rupture of membranes – a multicentre, double-blind, placebo-controlled,
agement of PPROM cases at 28–31 weeks’ gestation is associated randomized trial. Dexiprom Study Group. South African Medical Journal
with improved neonatal outcome in comparison to the neonatal Ramsey PS, Lieman JM, Brumfield CG, Carlo W. 2005. Chorioamnionitis
outcome of SPTL cases at the same gestational age. This does not increases neonatal morbidity in pregnancies complicated by preterm
hold true at 32–34 weeks’ gestation. We also found higher rates of premature rupture of membranes. American Journal of Obstetrics and
chorioamnionitis and a higher incidence of neonatal sepsis to be Gynecology 192:1162–1166.
Ramsey PS, Nuthalapaty FS, Lu G, Ramin S, Nuthalapaty ES, Ramin KD.
associated with prolonged latency rates at 32–34 weeks’ gestation, 2004. Contemporary management of preterm premature rupture of
indicating that expectant management might be counterproduc- membranes (PPROM): a survey of maternal-fetal medicine providers.
tive and call for judicious decision-making. American Journal of Obstetrics and Gynecology 191:1497–1502.
6 Z. Tsafrir et al.
Royal College of Obstetricians and Gynaecologists: Preterm Prelabour Rup- Tanir HM, Sener T, Tekin N, Aksit A, Ardic N. 2003. Preterm premature
ture of Membranes. Gren-top Guideline No.44, November 2006. rupture of membranes and neonatal outcome prior to 34 weeks
Sciscione A, Hoffman M, Paul D, Adu-Amankwa B, Sciscione J, gestation. International Journal of Gynecology and Obstetrics 82;
Merriman J. 2008. Outcomes in very low birth weight (VLBW) infants 167–172.
who delivered as a result of preterm rupture of the membranes versus Test G, Levy A, Wiznitzer A, Mazor M, Holcberg G, Zlotnik A et al. 2011.
preterm labor (PTL). American Journal of Obstetrics and Gynecology Factors affecting the latency period in patients with preterm premature
199 Supplement A:S51. rupture of membranes. Archives of Gynecology and Obstetrics 283:
Sims EJ, Vemillion ST, Soper DE. 2002. Preterm premature rupture of the 707–710.
membranes is associated with a reduction in neonatal respiratory distress Van Der Ham DP, Vijgen SM, Nijhuis JG, Van Beek JJ, Opmeer BC,
syndrome. American Journal of Obstetrics and Gynecology 187:268–272. Mulder AL et al. 2012. Induction of labor versus expectant
Spinnato JA, Shaver DC, Bray EM, Lipshitz J. 1987. Preterm premature management in women with preterm prelabor rupture of membranes
rupture of the membranes with fetal pulmonary maturity present: a pro- between 34 and 37 weeks: a randomized controlled trial. PloS Medicine
spective study. Obstetrics and Gynecology 69:196–201. 9:e1001208.
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