Research

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OBSTETRICS

Expectant management of preterm premature rupture

of membranes: is it all about gestational age?
Nir Melamed, MD, MSc; Avi Ben-Haroush, MD, MSc; Joseph Pardo, MD;
Rony Chen, MD; Eran Hadar, MD; Moshe Hod, MD; Yariv Yogev, MD
OBJECTIVE: We sought to compare neonatal outcome in cases of uncomplicated preterm premature rupture of membranes (PPROM) (ie, no
evidence of clinical chorioamnionitis, placental abruption, or fetal distress) with that of spontaneous preterm deliveries (PTDs) and to determine the effect of the latency period.

.001), mortality (1.6% vs 0.0%; P .001), respiratory morbidity

(32.8% vs 26.4%; P .006), necrotizing enterocolitis, jaundice, hypoglycemia, hypothermia, and polycythemia. Neonatal adverse outcome
was more likely in cases of latency period 7 days, oligohydramnios,
male fetus, and nulliparity.

STUDY DESIGN: The study group included women with PPROM at ges-

CONCLUSION: Consultation regarding prematurity-related morbidity in

infants exposed to uncomplicated PPROM cannot be extrapolated from
PTDs and should be stratified by the duration of the latency period and
the other risk factors identified in the current study.

tational age 280/7-336/7 weeks (n 488). Neonatal outcome was compared with a matched control group of women with spontaneous PTD (n
1464).
RESULTS: Neonates in the uncomplicated PPROM group were at in-

creased risk for composite adverse outcome (53.7% vs 42.0%; P

Key words: latency, neonatal, outcome, preterm premature rupture

of membranes

Cite this article as: Melamed N, Ben-Haroush A, Pardo J, et al. Expectant management of preterm premature rupture of membranes: is it all about gestational
age? Am J Obstet Gynecol 2010;203:x.ex-x.ex.

reterm premature rupture of membranes (PPROM) complicates 1-3%

of all pregnancies,1-4 and is associated
with maternal and perinatal morbidity
and mortality.2,5 The optimal management of pregnancies complicated by
PPROM remains unclear. Specifically,
the issue of expectant management vs
immediate delivery, especially in cases of
PPROM occurring at 30 weeks of gestation, is controversial.6-11
In cases of preterm labor, perinatal
outcome is largely affected by gestational
age at delivery. For that reason, the common practice in cases of uncomplicated

From the Department of Obstetrics and

Gynecology, Helen Schneider Hospital for
Women, Rabin Medical Center, and the
Sackler Faculty of Medicine, Tel Aviv
University, Tel Aviv, Israel.
Presented at the 30th Annual Meeting of the
Society for MaternalFetal Medicine, Chicago,
IL, Feb. 1-6, 2010.
Received April 12, 2010; revised June 20,
2010; accepted Aug. 16, 2010.
Reprints not available from the authors.
0002-9378/$36.00
2010 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2010.08.021

PPROM (ie, no evidence of clinical chorioamnionitis, placental abruption, or

fetal distress) is expectant management,
followed by labor induction when the
risks of amnionitis exceeds the risk of
prematurity, usually at around 32-34
weeks of gestation.
Nevertheless, it has been previously
shown that a significant proportion of
pregnancies with uncomplicated PPROM
may involve subclinical chorioamnionitis.12-15 Thus, considering the potential
unfavorable intrauterine environment
in the case of uncomplicated PPROM, it
is uncertain whether neonatal outcome
in these pregnancies can be directly extrapolated from that of newborns following spontaneous preterm labor at
similar gestational age. Furthermore, it is
possible that in cases of expectant management of uncomplicated PPROM, it is
not only gestational age at delivery that
should be taken into consideration, but
also the duration of the latency period
through which the fetus is exposed to
a potentially unfavorable intrauterine
environment.
Our aim was to compare neonatal outcome in cases of uncomplicated PPROM
with that of spontaneous low-risk preterm

deliveries (PTDs) at an equivalent gestational age, and to determine the effect of

the latency period on neonatal outcome.

M ATERIALS AND M ETHODS

We conducted a retrospective cohort study
in a single tertiary center from January
1995 through December 2007. The study
group included all women diagnosed with
PPROM at gestational age of 280/7-336/7
weeks (PPROM group). We did not include cases of PPROM at 28 weeks because the controversy regarding expectant
management vs immediate delivery in this
subgroup is of less relevance. The control
group was composed of the women presenting with spontaneous PTD (SPTD)
immediately following each of the
PPROM cases in the delivery logbook,
matched by gestational age at delivery in a
3:1 ratio (SPTD group). Only low-risk
women were included in the study and
control groups; women with chronic hypertension, pregnancy-induced hypertensive complications, gestational or pregestational diabetes, placenta previa, placental
abruption, amnionitis, oligohydramnios
(only for the control group), multiple gestations, intrauterine growth restriction at
presentation (birthweight 10th percen-

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TABLE 1

Demographic and obstetric characteristics

of women in PPROM and SPTD groups
Characteristic

PPROM group
n 488

Maternal age, y

29.9 5.0

SPTD group
n 1464
29.6 5.4

P value
.2

.....................................................................................................................................................................................................................................

Age 35 y

80 (16.4)

219 (15.0)

.4

204 (41.8)

948 (64.8)

.001

..............................................................................................................................................................................................................................................

Nulliparity

..............................................................................................................................................................................................................................................

32.5 1.8

32.5 1.8

N/A

28

20 (4.1)

60 (4.1)

N/A

29

32 (6.6)

96 (6.6)

N/A

30

44 (9.0)

132 (9.0)

N/A

31

28 (5.7)

84 (5.7)

N/A

32

60 (12.3)

180 (12.3)

N/A

33

84 (17.2)

252 (17.2)

N/A

34

220 (45.1)

660 (45.1)

N/A

Gestational age at delivery, wk

.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................

..............................................................................................................................................................................................................................................

Operative vaginal delivery

12 (2.5)

39 (2.7)

.8

212 (43.4)

879 (60.0)

.001

1876 431

1869 631

.9

..............................................................................................................................................................................................................................................

Cesarean section

..............................................................................................................................................................................................................................................

Birthweight, g

..............................................................................................................................................................................................................................................
a

Oligohydramnios

160 (32.8)

N/A

N/A

..............................................................................................................................................................................................................................................

Latency period, d

8.2 10.0

N/A

N/A

190 (38.9)

N/A

N/A

2-7

124 (25.5)

N/A

N/A

174 (35.7)

N/A

N/A

.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................

..............................................................................................................................................................................................................................................

Data presented as mean SD or n (%).

N/A, not applicable; PPROM, preterm premature rupture of membranes; SPTD, spontaneous preterm delivery.
a

Amniotic fluid index 50 mm at admission; women with oligohydramnios were excluded from control group.

Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

tile), cord pH 7.0, or 5-minute Apgar

score 7 were excluded from both groups.
The study protocol was approved by the
local institutional review board.
Data were collected from patients
hospital charts and from the institutional computerized perinatal database.
Neonatal outcome was compared between the study and control groups,
stratified by gestational age at delivery
and duration of the latency period.
PPROM was defined as spontaneous
rupture of membranes occurring before
the onset of active labor and 370/7 weeks
of gestation. The diagnosis of PPROM was
established on the basis of a history suggesting amniotic fluid leakage and a sterile
speculum examination demonstrating either amniotic fluid passing through the
cervix or fluid accumulation in the posterior vaginal fornix, and was confirmed by
1.e2

nitrazine paper reaction and ferning pattern when necessary.

The latency period was defined as the
time elapsed between onset of PPROM
to spontaneous delivery, labor induction
at 340/7 weeks, or indicated delivery
340/7 weeks. Gestational age was determined by the patients last menstrual period and, when available, confirmed by
first-trimester ultrasound. Chorioamnionitis was diagnosed on a clinical basis
that included maternal fever (38C),
leukocytosis, fetal tachycardia, uterine
tenderness, or foul-smelling amniotic
fluid with no other source of infection.
Respiratory morbidity was defined as
any of the following: the presence of
respiratory distress syndrome, transient
tachypnea of the newborn, bronchopulmonary dysplasia (BPD), apnea, or need
for ventilatory support. Infectious mor-

American Journal of Obstetrics & Gynecology MONTH 2010

bidity was defined as the presence of culture-proven sepsis, meningitis, or pneumonia. Neurologic morbidity included
convulsions, hypotonia, intraventricular
hemorrhage (any grade), or periventricular leukomalacia (PVL). Composite
neonatal outcome was defined as the
presence of any of the following: respiratory, infectious, or neurologic morbidity
(as defined above); neonatal death;
necrotizing enterocolitis (NEC); need
for phototherapy; hypoglycemia16; or
hypothermia.17
According to our departmental protocol, all women with suspected PPROM at
gestational age 340/7 weeks who are not
in active labor and do not have signs of
chorioamnionitis or placental abruption
are admitted for expectant management,
as follows. First, betamethasone is administrated at gestational age 240/7 and
340/7 weeks (12 mg of intramuscular
Celestone chronodose [Schering-Plough
Lab N.V., Brussels, Belgium] given twice
at a 24-hour interval). Second, antibiotic
treatment is initiated with intravenous
ampicillin (2 g 4 times daily) and oral
roxithromycin (150 mg twice daily) for
48 hours, followed by oral amoxicillin
(250 mg 3 times daily) and oral roxithromycin (150 mg twice daily) for 5 days.
Third, vaginal culture is taken at diagnosis of PPROM, and carriers of group B
streptococcus (GBS) are identified and
treated during labor.18 If culture results
are unavailable, patients are treated empirically with intravenous ampicillin
during labor. Fourth, routine daily follow-up is conducted for evidence of active labor, infection, or well-being. Follow-up includes examination of body
temperature, pulse, blood pressure,
uterine tenderness, white blood cell
count, nonstress test (twice a day), biophysical profile (twice a week), and estimated fetal weight evaluation (every
10-14 days). Vaginal examinations are
avoided as long as the patient is asymptomatic and free of contractions. When
indicated, sterile visual inspection of the
cervix is preferred over digital examination. Fifth, labor is induced at 340/7
weeks, either by vaginal prostaglandin
E2 tablets or oxytocin. Cesarean section
is performed on the basis of obstetric indications. Tocolytic treatment is avoided

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FIGURE 1

Neonatal outcome in cases of PPROM and PTL

Neonatal outcome in preterm premature rupture of membranes (PPROM) (squares) and preterm labor
(PTL) (triangles) groups. Data reflect rate of composite neonatal outcome, stratified by gestational age.
*
P .05.
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

in cases of PPROM. Women presenting

with preterm labor are treated with betamethasone (as described above) and tocolysis (indomethacin, nifedipine, or
oxytocin antagonists).
Data analysis was performed with software (SPSS, version 15.0; SPSS, Inc, Chicago, IL). One-way analysis of variance
and Student t test were used to compare
continuous variables between groups,
and 2 test was used for categorical variables. Multivariate logistic regression
analysis was used to identify factors that
are associated with adverse neonatal outcome in cases of PPROM and to determine whether the association of the
duration of the latency period with neonatal outcome is independent. Relative
risks were estimated based on the odds
ratios (ORs) using the Zhang and Yu
method.19 Differences were considered
significant when the P value was .05.

R ESULTS
Demographic and obstetric
characteristics
Of the total of 83,118 deliveries during
the study period, the rate of PPROM was
1.5% (n 1247), of which 39.1% (488/

1247) were eligible for the study (711

cases occurred 340/7 weeks, and 48
cases were either high-risk pregnancies
or complicated by clinical chorioamnionitis). The demographic and obstetric
characteristics of the women in the
PPROM group and the control group
(women presenting with SPTD, matched
by gestational age at delivery in a 3:1 ratio,
n 1464) are summarized in Table 1. The
PPROM group was characterized by a
lower proportion of nulliparous women
and a lower rate of delivery by cesarean
section.

Neonatal outcome
The rate of adverse neonatal outcome
was higher in cases of uncomplicated
PPROM compared with cases of SPTD
(Figure 1). Specifically, neonates in the
PPROM group were characterized by a
higher neonatal mortality rate, were
more likely to be admitted to neonatal
intensive care unit, and demonstrated a
higher rate of respiratory morbidity,
neurologic morbidity, and other prematurity-related complications including
NEC, jaundice requiring phototherapy,
hypoglycemia, hypothermia, and poly-

Research

cythemia (Table 2). The rate of infectious morbidity was similar in the
PPROM and the SPTD groups (Table 2).
We used logistic regression analysis to
control for potential confounders including maternal age, parity, gestational
age at delivery, fetal sex, and birthweight.
Uncomplicated PPROM was associated
with increased risk for composite neonatal outcome (OR, 1.7; 95% confidence
interval [CI], 1.4 2.2) and respiratory
morbidity (OR, 1.4; 95% CI, 1.11.7)
compared with SPTD. We then used the
same analysis to isolate the association of
PPROM with adverse neonatal outcome
from the possible adverse effects of a prolonged latency period by assessing the association of PPROM with a latency period of 2 days (representing the
isolated effect of PPROM) against the
background of SPTD at the same gestational week. Even in the absence of a significant latency period (ie, 2 days)
PPROM was independently associated
with increased risk for adverse neonatal
outcome (OR, 1.4; 95% CI, 1.11.9).

The effect of the latency period

We next sought to assess the effect of the
latency period in cases with uncomplicated PPROM on the risk of adverse neonatal outcome. Neonatal outcome was
stratified by gestational age at delivery
and duration of the latency period (Figures 2 and 3). The rate of composite neonatal outcome was higher when the latency period was 7 days (Figure 2).
Similarly, the rate of respiratory morbidity was consistently higher when the latency period following PPROM was 7
days, independently of gestational age at
delivery (Figure 3). The risk of neonatal
infectious morbidity (after exclusion of
cases of clinical chorioamnionitis, as described in the Materials and Methods
section) was not related to the duration
of the latency period (Figure 3). Neurologic morbidity was found to be more
common in cases of prolonged latency
period for neonates delivered at gestational age of 28-32 weeks (Figure 3).
Risk factors for adverse neonatal
outcome in cases of PPROM
To better characterize cases with uncomplicated PPROM that are at increased

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TABLE 2

Short-term neonatal outcome in PPROM and SPTD groups

Outcome
Hospital stay, d

PPROM group n 488

25.6 24.2

SPTD group n 1464

22.4 20.7

OR (95% CI)

P value

N/A

.005

N/A

.001

................................................................................................................................................................................................................................................................................................................................................................................

Admission to NICU

488 (100)

925 (63.2)

Composite neonatal outcome

262 (53.7)

615 (42.0)

8 (1.6)

0 (0.0)

160 (32.8)

387 (26.4)

1.4 (1.11.7)

.006

RDS

76 (15.6)

176 (12.0)

1.4 (1.11.8)

.04

TTN

37 (7.6)

114 (7.8)

1.0 (0.71.4)

.9

Mechanical ventilation

83 (17.0)

96 (6.6)

2.9 (2.14.0)

.001

Apnea or cyanotic events

28 (5.7)

6 (0.4)

14.8 (6.135.9)

.001

................................................................................................................................................................................................................................................................................................................................................................................
a

1.6 (1.32.0)

.001

................................................................................................................................................................................................................................................................................................................................................................................
b

Neonatal death

N/A

.001

................................................................................................................................................................................................................................................................................................................................................................................

Respiratory morbidity

.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................

Pneumothorax

3 (0.6)

16 (1.1)

0.6 (0.21.9)

.4

21 (4.3)

30 (2.0)

2.1 (1.23.8)

.007

17 (3.5)

72 (4.9)

0.7 (0.41.2)

.2

429 (88.0)

486 (33.2)

14.6 (10.919.6)

.001

.......................................................................................................................................................................................................................................................................................................................................................................

BPD

................................................................................................................................................................................................................................................................................................................................................................................

Infectious morbidity

.......................................................................................................................................................................................................................................................................................................................................................................

Sepsis workup

.......................................................................................................................................................................................................................................................................................................................................................................

Culture-proven sepsis

12 (2.5)

63 (4.3)

0.6 (0.31.1)

.07

Pneumonia

5 (1.0)

12 (0.8)

1.3 (0.43.6)

.7

Meningitis

0 (0.0)

0 (0.0)

Neurologic morbidity

32 (6.6)

62 (4.2)

1.6 (1.12.5)

.04

Convulsions

8 (1.6)

36 (2.5)

0.7 (0.31.4)

.3

Hypotonia

8 (1.6)

9 (0.6)

2.7 (1.17.0)

.03

24 (4.9)

48 (3.3)

1.5 (0.92.5)

.09

4 (0.8)

0 (0.0)

.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................

N/A

N/A

................................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................

IVH grade 1-2

.......................................................................................................................................................................................................................................................................................................................................................................

PVL

N/A

.001

................................................................................................................................................................................................................................................................................................................................................................................

Additional morbidities

.......................................................................................................................................................................................................................................................................................................................................................................

52 (10.7)

81 (5.5)

2.0 (1.42.9)

.001

Jaundice requiring phototherapy

183 (37.5)

426 (29.1)

1.5 (1.21.8)

.001

Hypoglycemia

108 (22.1)

111 (7.6)

3.5 (2.64.6)

.001

Hypothermia

20 (4.1)

0 (0.0)

Polycythemia

20 (4.1)

18 (1.2)

3.4 (1.86.5)

Anemia requiring blood transfusion

28 (5.7)

120 (8.2)

0.7 (0.41.1)

NEC

.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................
.......................................................................................................................................................................................................................................................................................................................................................................

N/A

.001

.......................................................................................................................................................................................................................................................................................................................................................................

.001

.......................................................................................................................................................................................................................................................................................................................................................................

.08

................................................................................................................................................................................................................................................................................................................................................................................

Data presented as mean SD or n (%).

BPD, bronchopulmonary dysplasia; CI, confidence interval; IVH, intraventricular hemorrhage; N/A, not applicable; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; OR, odds ratio;
PPROM, preterm premature rupture of membranes; PVL, periventricular leukomalacia; RDS, respiratory distress syndrome; SPTD, spontaneous preterm delivery; TTN, transient tachypnea of
newborn.
a

As defined in Materials and Methods section; b Refers to infants not discharged.

Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

risk for adverse neonatal outcome (independently of overt complications, eg,

clinical chorioamnionitis and placental
abruption), we used multivariable logistic regression analysis to identify risk factors for composite neonatal adverse outcome and respiratory morbidity (Table
3). Other than the obvious relationship
to gestational age, composite neonatal
adverse outcome and respiratory morbidity were more likely when oligohy1.e4

dramnios was noted at presentation,

with a prolonged latency period (7
days), and with male fetal sex (Table 3).
Nulliparity and a positive GBS carrier
status were additional risk factors for
composite neonatal adverse outcome.
Maternal age, birthweight, mode of delivery, and administration of betamethasone were unrelated to adverse outcome
in this selective group of cases with uncomplicated PPROM (Table 3).

American Journal of Obstetrics & Gynecology MONTH 2010

Maturity vs latency
Considering the finding that prolonged
latency (at each given gestational age at
delivery) is associated with increased risk
for adverse neonatal outcome, the overall effect of the latency period on neonatal outcome in women who present with
PPROM can be considered as a combination of the beneficial effects (ie, more
advanced fetal maturity) and the negative effects (as described above, Figures 2

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FIGURE 2

The effect of the latency period on composite neonatal outcome

Effect of prolonged latency period (7 days; circles) on neonatal outcome in cases of preterm
premature rupture of membranes. Data reflect rate of composite neonatal outcome, stratified by
duration of latency period (7 [squares] and 7 days) and gestational age. Rate of adverse neonatal
outcome in preterm labor (PTL) (triangles) group is presented for comparison.
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

and 3). Thus, we questioned whether, at

a certain gestational age, the negative effects of prolonged latency in cases of expectant management of PPROM may
outweigh the beneficial effects of more
advanced fetal maturity.
For that purpose, for each subgroup of
women who presented with PPROM at
the same gestational age (28, 29, 30, 31,
32, or 33 weeks), we analyzed the overall
effect of the duration of the latency period on neonatal outcome (Figure 4). We
identified a clear trend of decreased rate
of adverse neonatal outcome with increasing duration of the latency period,
irrespective of gestational age at presentation with PPROM. Thus, it appears
that for women with uncomplicated
PPROM at gestational age 28-33 weeks,
the overall effect of expectant management is beneficial, despite the potential
negative effects associated with prolonged latency.

C OMMENT
In the current study we hypothesized
that, considering the potential differences in the intrauterine environment,

neonatal outcome in cases of uncomplicated PPROM may be less favorable than

that of newborns following SPTD at similar gestational age, especially in cases of
a prolonged latency period. Our main
findings were as follows. First, the rate
of adverse neonatal outcome is about
70% higher in cases of uncomplicated
PPROM compared with that of SPTD.
Second, prolonged latency (7 days),
oligohydramnios, male fetal sex, nulliparity, and a GBS carrier status are associated with increased risk for adverse
neonatal outcome in cases of uncomplicated PPROM, independently of gestational age. Third, for women with uncomplicated PPROM at gestational age
28-33 weeks, the benefit of more advanced fetal maturity associated with expectant management appear to outweigh the potential harming effect of a
prolonged latency period.
We were able to identify only 1 study
comparing neonatal outcome in cases of
PPROM with that of neonates following
SPTD. Newman et al20 compared neonatal outcome in cases of PPROM at gestational age of 23-27 weeks with that of

Research

PTD with intact membranes at similar

gestational age. They found the rate of
chorioamnionitis and adverse neonatal
outcome to be higher in the PPROM
group. However, this study is limited by
referring to only a small number of neonatal outcome parameters (Apgar score,
chorioamnionitis, and mortality), as
well as by the lack of information regarding the latency period in the PPROM
group. Furthermore, in contrast to our
study, the authors did not limit the study
to cases of uncomplicated PPROM, so
that the differences in perinatal outcome
can be the result of multiple factors other
than the intrauterine environment (ie,
placental abruption, clinical chorioamnionitis, and cord prolapse).
The reason for the higher rate of adverse neonatal outcome in cases of uncomplicated PPROM is unclear. One
possible explanation is the presence of
subclinical chorioamnionitis, which has
been shown to complicate up to 25-40%
of cases of PPROM.13-15 Recent studies
have shown that the indolent inflammatory environment and the presence of
various proinflammatory mediators and
cytokines in cases of subclinical chorioamnionitis may be associated with shortand long-term adverse neonatal outcome, including neurological injury
(PVL and intraventricular hemorrhage),21-25 lung injury (BPD),21,23,26-31
NEC,25 and infectious morbidity.25,32
The findings in the current study of a
higher rate of BPD, PVL, and NEC in the
PPROM group, and the association of a
GBS carrier status with adverse neonatal
outcome in the PPROM group provide
some support to this hypothesis.
We have also hypothesized that if it is
the differences in the intrauterine environment that are responsible for the lessfavorable outcome in cases of uncomplicated PPROM, then the duration
through which the fetus is exposed to
this environment (ie, the latency period)
will affect neonatal outcome. Indeed, we
have found that in cases of uncomplicated PPROM, a prolonged latency period, for each given gestational age at delivery, is an independent risk factor for
adverse neonatal outcome (Figures 2 and
3). For illustration, in a case of PPROM
at 28 weeks that culminates in delivery at

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FIGURE 3

The effect of the latency period on specific neonatal outcomes

Effect of prolonged latency period (7 days; dark bars) on neonatal respiratory, neurologic, and
infectious morbidity in cases of preterm premature rupture of membranes. Data are stratified by
latency period (7 [light bars] and 7 days) and gestational age at delivery.
*P .05.
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

32 weeks, neonatal outcome appears to

be less favorable than in the case of
PPROM at 31 weeks that also results in
delivery at 32 weeks of gestation. Another possible explanation for this observation is the higher probability for sub-

clinical intraamniotic infection as the

duration of the latency period increases.
Thus, it appears that expectant management in cases of PPROM is associated
with 2 opposing effects on neonatal outcomea beneficial effect resulting from

the more advanced fetal maturity

achieved, and a negative effect that may
be related to the prolonged fetal exposure to an unfavorable intrauterine environment (as described in the preceding
paragraph). To determine whether, at a
certain gestational age, the negative effects of expectant management outweigh
its beneficial effects, we compared the
outcome of cases of PPROM that occurred in the same gestational week and
were followed by latency periods of different durations (Figure 4). Our results
suggest that for women presenting with
PPROM at gestational age 28-33 weeks,
in the absence of PPROM-related complications (ie, chorioamnionitis, placental abruption, and cord prolapse), the
overall effect of expectant management
is beneficial. For illustration, when 2
cases of PPROM at 28 weeks of gestation
are managed expectantly, the case that
results in delivery at 30 weeks of gestation appears to be associated with lessfavorable neonatal outcome compared
with the case that results in delivery at 32
weeks of gestation, even though the neonate in the latter case might have been
exposed to an unfavorable intrauterine
environment for a longer period of time.
Thus, it can be deduced that these results
do not provide support for a practice of
immediate delivery in cases of PPROM
at gestational age of 28-33 weeks. Nevertheless, because of our selective study
population and the retrospective design,
our results cannot be used to determine

TABLE 3

Factors predicting adverse neonatal outcome in cases of preterm premature rupture of membranes
Composite neonatal outcomea

Respiratory morbiditya

Risk factors

OR
(95% CI)

Estimated RR
(95% CI)b

Risk factors

OR
(95% CI)

Estimated RR
(95% CI)b

Nulliparity

3.1 (1.85.5)

1.7 (1.42.0)

Oligohydramnios (AFI 50 mm)

2.5 (1.44.5)

1.8 (1.32.3)

Oligohydramnios (AFI 50 mm)

2.8 (1.55.3)

1.9 (1.32.5)

Male sex

2.1 (1.64.4)

1.4 (1.31.8)

GBS carrier

2.7 (1.34.8)

2.5 (1.34.0)

Latency period 7 d

1.9 (1.13.3)

1.5 (1.11.9)

Latency period 7 d

1.7 (1.12.8)

1.4 (1.11.8)

Gestational wk

0.6 (0.50.8)

N/A

Male sex

1.7 (1.13.2)

1.3 (1.11.7)

Gestational wk

0.6 (0.40.7)

N/A

................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................
................................................................................................................................................................................................................................................................................................................................................................................

AFI, amniotic fluid index; CI, confidence interval; GBS, group B streptococcus; N/A, not applicable; OR, odds ratio; RR, relative risk.
Values reflect results of multivariable logistic regression analysis.
a

As defined in Materials and Methods section; b Estimations of relative risk were made using Zhang and Yu method.19

Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

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Research

the other risk factors for adverse outcome identified in the current study.
Further prospective studies are needed
to validate our observations and to
define the reasons for the less-favorable neonatal outcome in cases of
PPROM.
f

FIGURE 4

Overall effect of duration of latency period on neonatal

outcome in cases of expectant management of PPROM

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Overall effect of latency period on neonatal outcome reflects combination of beneficial effects (ie,
more advanced fetal maturity) and negative effects associated with prolonged latency (see text and
Figures 2 and 3). Separate analysis was performed for each subgroup of women presenting with
PPROM at same gestational age (28 weeks [open squares], 29 weeks [diamonds], 30 weeks [open
circles], 31 weeks [X], 32 weeks [solid squares], and 33 weeks [solid circles]). For purpose of
comparison, rate of composite adverse neonatal outcome for women in spontaneous preterm delivery
(SPTD) group at each gestational week is presented on left side of graph.
*P .05.
PPROM, preterm premature rupture of membranes.
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2010.

the optimal management for women

presenting PPROM at these gestational
weeks.
The reason for the association of oligohydramnios with adverse neonatal
outcome in cases of uncomplicated
PPROM is not entirely clear. It is possible that oligohydramnios, as well as a
GBS carrier status, which are wellknown risk factors for intraamniotic infection in cases of PPROM, also increase
the risk for subclinical chorioamnionitis.33-35 The association of fetal male gender with adverse neonatal outcome in
the PPROM group may be explained by
the observation made in previous studies
that fetal male gender is an independent
risk factor for adverse neonatal outcome
in cases of PTD in general.36

In conclusion, we have found that the

rate of adverse neonatal outcome is
higher in cases of PPROM at gestational
age 28-33 weeks compared with cases of
SPTD at the same gestational age, even in
the absence of PPROM-related complications, and that the outcome is even less
favorable in cases of prolonged latency,
oligohydramnios, male fetal sex, nulliparity, and a GBS carrier status. Thus,
when providing consultation to patients
presenting with PPROM, information
regarding the predicted neonatal outcome cannot be directly extrapolated
from studies of PTD. Instead, the prognostic information should be based on
data obtained from cases of PPROM,
and should be further stratified by the
duration of the latency period as well as

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