Research www. AJOG.

org

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 un-
complicated preterm premature rupture of membranes (PPROM) (ie, no
evidence of clinical chorioamnionitis, placental abruption, or fetal dis-
tress) with that of spontaneous preterm deliveries (PTDs) and to deter-
mine the effect of the latency period.
STUDY DESIGN: The study group included women with PPROM at ges-
tational age 280/7-336/7 weeks (n ⫽ 488). Neonatal outcome was com-
pared 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 ⬍
.001), mortality (1.6% vs 0.0%; P ⬍ .001), respiratory morbidity
(32.8% vs 26.4%; P ⫽ .006), necrotizing enterocolitis, jaundice, hypo-
glycemia, hypothermia, and polycythemia. Neonatal adverse outcome
was more likely in cases of latency period ⬎7 days, oligohydramnios,
male fetus, and nulliparity.
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.
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 2011;204:48.e1-8.

P reterm premature rupture of mem-

branes (PPROM) complicates 1-3%
of all pregnancies,1-4 and is associated
with maternal and perinatal morbidity
and mortality.2,5 The optimal manage-
ment of pregnancies complicated by
PPROM remains unclear. Specifically,
the issue of expectant management vs
immediate delivery, especially in cases of
PPROM occurring at ⱖ30 weeks of ges-
tation, is controversial.6-11
In cases of preterm labor, perinatal
outcome is largely affected by gestational
age at delivery. For that reason, the com-
mon 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 Maternal-Fetal 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
© 2011 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2010.08.021
PPROM (ie, no evidence of clinical cho-
rioamnionitis, 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 chorioamnioni-
tis.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 ex-
trapolated from that of newborns fol-
lowing spontaneous preterm labor at
similar gestational age. Furthermore, it is
possible that in cases of expectant man-
agement 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 out-
come in cases of uncomplicated PPROM
with that of spontaneous low-risk preterm
deliveries (PTDs) at an equivalent gesta-
tional 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 in-
clude cases of PPROM at ⬍28 weeks be-
cause the controversy regarding expectant
management vs immediate delivery in this
subgroup is of less relevance. The control
group was composed of the women pre-
senting 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 hy-
pertension, pregnancy-induced hyperten-
sive complications, gestational or pregesta-
tional diabetes, placenta previa, placental
abruption, amnionitis, oligohydramnios
(only for the control group), multiple ges-
tations, intrauterine growth restriction at
presentation (birthweight ⬍10th percen-

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www.AJOG.org Obstetrics Research

bidity was defined as the presence of cul-

TABLE 1 ture-proven sepsis, meningitis, or pneu-
Demographic and obstetric characteristics monia. Neurologic morbidity included
of women in PPROM and SPTD groups convulsions, hypotonia, intraventricular
PPROM group SPTD group hemorrhage (any grade), or periven-
Characteristic n ⴝ 488 n ⴝ 1464 P value tricular leukomalacia (PVL). Composite
Maternal age, y 29.9 ⫾ 5.0 29.6 ⫾ 5.4 .2 neonatal outcome was defined as the
.....................................................................................................................................................................................................................................
Age ⬎35 y 80 (16.4) 219 (15.0) .4 presence of any of the following: respira-
..............................................................................................................................................................................................................................................
tory, infectious, or neurologic morbidity
Nulliparity 204 (41.8) 948 (64.8) ⬍ .001
.............................................................................................................................................................................................................................................. (as defined above); neonatal death;
Gestational age at delivery, wk 32.5 ⫾ 1.8 32.5 ⫾ 1.8 N/A necrotizing enterocolitis (NEC); need
.....................................................................................................................................................................................................................................
28 20 (4.1) 60 (4.1) N/A for phototherapy; hypoglycemia16; or
.....................................................................................................................................................................................................................................
29 32 (6.6) 96 (6.6) N/A hypothermia.17
.....................................................................................................................................................................................................................................
According to our departmental proto-
30 44 (9.0) 132 (9.0) N/A
..................................................................................................................................................................................................................................... col, all women with suspected PPROM at
31 28 (5.7) 84 (5.7) N/A
.....................................................................................................................................................................................................................................
gestational age ⬍340/7 weeks who are not
32 60 (12.3) 180 (12.3) N/A in active labor and do not have signs of
.....................................................................................................................................................................................................................................
33 84 (17.2) 252 (17.2) N/A chorioamnionitis or placental abruption
.....................................................................................................................................................................................................................................
are admitted for expectant management,
34 220 (45.1) 660 (45.1) N/A
.............................................................................................................................................................................................................................................. as follows. First, betamethasone is ad-
Operative vaginal delivery 12 (2.5) 39 (2.7) .8
..............................................................................................................................................................................................................................................
ministrated at gestational age ⬎240/7 and
Cesarean section 212 (43.4) 879 (60.0) ⬍ .001 ⬍340/7 weeks (12 mg of intramuscular
..............................................................................................................................................................................................................................................
Birthweight, g 1876 ⫾ 431 1869 ⫾ 631 .9 Celestone chronodose [Schering-Plough
..............................................................................................................................................................................................................................................
a
Lab N.V., Brussels, Belgium] given twice
Oligohydramnios 160 (32.8) N/A N/A
.............................................................................................................................................................................................................................................. at a 24-hour interval). Second, antibiotic
Latency period, d 8.2 ⫾ 10.0 N/A N/A treatment is initiated with intravenous
.....................................................................................................................................................................................................................................
⬍2 190 (38.9) N/A N/A ampicillin (2 g 4 times daily) and oral
.....................................................................................................................................................................................................................................
2-7 124 (25.5) N/A N/A roxithromycin (150 mg twice daily) for
.....................................................................................................................................................................................................................................
48 hours, followed by oral amoxicillin
⬎7 174 (35.7) N/A N/A
.............................................................................................................................................................................................................................................. (250 mg 3 times daily) and oral roxithro-
Data presented as mean ⫾ SD or n (%). mycin (150 mg twice daily) for 5 days.
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.
Third, vaginal culture is taken at diagno-
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2011. sis of PPROM, and carriers of group B
streptococcus (GBS) are identified and
treated during labor.18 If culture results
tile), cord pH ⬍7.0, or 5-minute Apgar nitrazine paper reaction and ferning pat- are unavailable, patients are treated em-
score ⬍7 were excluded from both groups. tern when necessary. pirically with intravenous ampicillin
The study protocol was approved by the The latency period was defined as the during labor. Fourth, routine daily fol-
local institutional review board. time elapsed between onset of PPROM low-up is conducted for evidence of ac-
Data were collected from patient’s to spontaneous delivery, labor induction tive labor, infection, or well-being. Fol-
hospital charts and from the institu- at 340/7 weeks, or indicated delivery low-up includes examination of body
tional computerized perinatal database. ⬍340/7 weeks. Gestational age was deter- temperature, pulse, blood pressure,
Neonatal outcome was compared be- mined by the patient’s last menstrual pe- uterine tenderness, white blood cell
tween the study and control groups, riod and, when available, confirmed by count, nonstress test (twice a day), bio-
stratified by gestational age at delivery first-trimester ultrasound. Chorioam- physical profile (twice a week), and esti-
and duration of the latency period. nionitis was diagnosed on a clinical basis mated fetal weight evaluation (every
PPROM was defined as spontaneous that included maternal fever (⬎38°C), 10-14 days). Vaginal examinations are
rupture of membranes occurring before leukocytosis, fetal tachycardia, uterine avoided as long as the patient is asymp-
the onset of active labor and ⬍370/7 weeks tenderness, or foul-smelling amniotic tomatic and free of contractions. When
of gestation. The diagnosis of PPROM was fluid with no other source of infection. indicated, sterile visual inspection of the
established on the basis of a history sug- Respiratory morbidity was defined as cervix is preferred over digital examina-
gesting amniotic fluid leakage and a sterile any of the following: the presence of tion. Fifth, labor is induced at 340/7
speculum examination demonstrating ei- respiratory distress syndrome, transient weeks, either by vaginal prostaglandin
ther amniotic fluid passing through the tachypnea of the newborn, bronchopul- E2 tablets or oxytocin. Cesarean section
cervix or fluid accumulation in the poste- monary dysplasia (BPD), apnea, or need is performed on the basis of obstetric in-
rior vaginal fornix, and was confirmed by for ventilatory support. Infectious mor- dications. Tocolytic treatment is avoided

JANUARY 2011 American Journal of Obstetrics & Gynecology 48.e2

Research Obstetrics
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 2011.
in cases of PPROM. Women presenting
with preterm labor are treated with beta-
methasone (as described above) and to-
colysis (indomethacin, nifedipine, or
oxytocin antagonists).
Data analysis was performed with soft-
ware (SPSS, version 15.0; SPSS, Inc, Chi-
cago, 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 vari-
ables. Multivariate logistic regression
analysis was used to identify factors that
are associated with adverse neonatal out-
come in cases of PPROM and to deter-
mine whether the association of the
duration of the latency period with neo-
natal 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/
48.e3 American Journal of Obstetrics & Gynecology JANUARY 2011
1247) were eligible for the study (711
cases occurred ⬎340/7 weeks, and 48
cases were either high-risk pregnancies
or complicated by clinical chorioamnio-
nitis). 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 prema-
turity-related complications including
NEC, jaundice requiring phototherapy,
hypoglycemia, hypothermia, and poly-
www.AJOG.org
cythemia (Table 2). The rate of infec-
tious morbidity was similar in the
PPROM and the SPTD groups (Table 2).
We used logistic regression analysis to
control for potential confounders in-
cluding maternal age, parity, gestational
age at delivery, fetal sex, and birthweight.
Uncomplicated PPROM was associated
with increased risk for composite neona-
tal outcome (OR, 1.7; 95% confidence
interval [CI], 1.4 –2.2) and respiratory
morbidity (OR, 1.4; 95% CI, 1.1–1.7)
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 pro-
longed latency period by assessing the as-
sociation of PPROM with a latency pe-
riod of ⬍2 days (representing the
isolated effect of PPROM) against the
background of SPTD at the same gesta-
tional week. Even in the absence of a sig-
nificant latency period (ie, ⬍2 days)
PPROM was independently associated
with increased risk for adverse neonatal
outcome (OR, 1.4; 95% CI, 1.1–1.9).
The effect of the latency period
We next sought to assess the effect of the
latency period in cases with uncompli-
cated PPROM on the risk of adverse neo-
natal outcome. Neonatal outcome was
stratified by gestational age at delivery
and duration of the latency period (Fig-
ures 2 and 3). The rate of composite neo-
natal outcome was higher when the la-
tency period was ⬎7 days (Figure 2).
Similarly, the rate of respiratory morbid-
ity was consistently higher when the la-
tency 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 de-
scribed in the “Materials and Methods”
section) was not related to the duration
of the latency period (Figure 3). Neuro-
logic morbidity was found to be more
common in cases of prolonged latency
period for neonates delivered at gesta-
tional age of 28-32 weeks (Figure 3).
Risk factors for adverse neonatal
outcome in cases of PPROM
To better characterize cases with uncom-
plicated PPROM that are at increased
www.AJOG.org Obstetrics Research

TABLE 2
Short-term neonatal outcome in PPROM and SPTD groups
Outcome PPROM group n ⴝ 488 SPTD group n ⴝ 1464 OR (95% CI) P value
Hospital stay, d 25.6 ⫾ 24.2 22.4 ⫾ 20.7 N/A .005
................................................................................................................................................................................................................................................................................................................................................................................
Admission to NICU 488 (100) 925 (63.2) N/A ⬍ .001
................................................................................................................................................................................................................................................................................................................................................................................
Composite neonatal outcome a
262 (53.7) 615 (42.0) 1.6 (1.3–2.0) ⬍ .001
................................................................................................................................................................................................................................................................................................................................................................................
Neonatal death b
8 (1.6) 0 (0.0) N/A ⬍ .001
................................................................................................................................................................................................................................................................................................................................................................................
Respiratory morbidity 160 (32.8) 387 (26.4) 1.4 (1.1–1.7) .006
.......................................................................................................................................................................................................................................................................................................................................................................
RDS 76 (15.6) 176 (12.0) 1.4 (1.1–1.8) .04
.......................................................................................................................................................................................................................................................................................................................................................................
TTN 37 (7.6) 114 (7.8) 1.0 (0.7–1.4) .9
.......................................................................................................................................................................................................................................................................................................................................................................
Mechanical ventilation 83 (17.0) 96 (6.6) 2.9 (2.1–4.0) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Apnea or cyanotic events 28 (5.7) 6 (0.4) 14.8 (6.1–35.9) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Pneumothorax 3 (0.6) 16 (1.1) 0.6 (0.2–1.9) .4
.......................................................................................................................................................................................................................................................................................................................................................................
BPD 21 (4.3) 30 (2.0) 2.1 (1.2–3.8) .007
................................................................................................................................................................................................................................................................................................................................................................................
Infectious morbidity 17 (3.5) 72 (4.9) 0.7 (0.4–1.2) .2
.......................................................................................................................................................................................................................................................................................................................................................................
Sepsis workup 429 (88.0) 486 (33.2) 14.6 (10.9–19.6) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Culture-proven sepsis 12 (2.5) 63 (4.3) 0.6 (0.3–1.1) .07
.......................................................................................................................................................................................................................................................................................................................................................................
Pneumonia 5 (1.0) 12 (0.8) 1.3 (0.4–3.6) .7
.......................................................................................................................................................................................................................................................................................................................................................................
Meningitis 0 (0.0) 0 (0.0) N/A N/A
................................................................................................................................................................................................................................................................................................................................................................................
Neurologic morbidity 32 (6.6) 62 (4.2) 1.6 (1.1–2.5) .04
.......................................................................................................................................................................................................................................................................................................................................................................
Convulsions 8 (1.6) 36 (2.5) 0.7 (0.3–1.4) .3
.......................................................................................................................................................................................................................................................................................................................................................................
Hypotonia 8 (1.6) 9 (0.6) 2.7 (1.1–7.0) .03
.......................................................................................................................................................................................................................................................................................................................................................................
IVH grade 1-2 24 (4.9) 48 (3.3) 1.5 (0.9–2.5) .09
.......................................................................................................................................................................................................................................................................................................................................................................
PVL 4 (0.8) 0 (0.0) N/A ⬍ .001
................................................................................................................................................................................................................................................................................................................................................................................
Additional morbidities
.......................................................................................................................................................................................................................................................................................................................................................................
NEC 52 (10.7) 81 (5.5) 2.0 (1.4–2.9) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Jaundice requiring phototherapy 183 (37.5) 426 (29.1) 1.5 (1.2–1.8) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Hypoglycemia 108 (22.1) 111 (7.6) 3.5 (2.6–4.6) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Hypothermia 20 (4.1) 0 (0.0) N/A ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Polycythemia 20 (4.1) 18 (1.2) 3.4 (1.8–6.5) ⬍ .001
.......................................................................................................................................................................................................................................................................................................................................................................
Anemia requiring blood transfusion 28 (5.7) 120 (8.2) 0.7 (0.4–1.1) .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 2011.

risk for adverse neonatal outcome (inde- dramnios was noted at presentation, Maturity vs latency
pendently of overt complications, eg, with a prolonged latency period (⬎7 Considering the finding that prolonged
clinical chorioamnionitis and placental days), and with male fetal sex (Table 3). latency (at each given gestational age at
abruption), we used multivariable logis- Nulliparity and a positive GBS carrier delivery) is associated with increased risk
tic regression analysis to identify risk fac- status were additional risk factors for for adverse neonatal outcome, the over-
tors for composite neonatal adverse out- composite neonatal adverse outcome. all effect of the latency period on neona-
come and respiratory morbidity (Table Maternal age, birthweight, mode of de- tal outcome in women who present with
3). Other than the obvious relationship livery, and administration of betametha- PPROM can be considered as a combi-
to gestational age, composite neonatal sone were unrelated to adverse outcome nation of the beneficial effects (ie, more
adverse outcome and respiratory mor- in this selective group of cases with un- advanced fetal maturity) and the nega-
bidity were more likely when oligohy- complicated PPROM (Table 3). tive effects (as described above, Figures 2

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Research Obstetrics www.AJOG.org

PTD with intact membranes at similar

FIGURE 2
gestational age. They found the rate of
The effect of the latency period on composite neonatal outcome 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 neo-
natal outcome parameters (Apgar score,
chorioamnionitis, and mortality), as
well as by the lack of information regard-
ing 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 chorioam-
nionitis, and cord prolapse).
The reason for the higher rate of ad-
verse neonatal outcome in cases of un-
complicated PPROM is unclear. One
possible explanation is the presence of
Effect of prolonged latency period (⬎7 days; circles) on neonatal outcome in cases of preterm subclinical chorioamnionitis, which has
premature rupture of membranes. Data reflect rate of composite neonatal outcome, stratified by been shown to complicate up to 25-40%
duration of latency period (ⱕ7 [squares] and ⬎7 days) and gestational age. Rate of adverse neonatal of cases of PPROM.13-15 Recent studies
outcome in preterm labor (PTL) (triangles) group is presented for comparison. have shown that the indolent inflamma-
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2011.
tory environment and the presence of
various proinflammatory mediators and
and 3). Thus, we questioned whether, at neonatal outcome in cases of uncompli- cytokines in cases of subclinical chorio-
a certain gestational age, the negative ef- cated PPROM may be less favorable than amnionitis may be associated with short-
fects of prolonged latency in cases of ex- that of newborns following SPTD at sim- and long-term adverse neonatal out-
pectant management of PPROM may ilar gestational age, especially in cases of come, including neurological injury
outweigh the beneficial effects of more a prolonged latency period. Our main (PVL and intraventricular hemor-
advanced fetal maturity. findings were as follows. First, the rate rhage),21-25 lung injury (BPD),21,23,26-31
For that purpose, for each subgroup of of adverse neonatal outcome is about NEC,25 and infectious morbidity.25,32
women who presented with PPROM at 70% higher in cases of uncomplicated The findings in the current study of a
the same gestational age (28, 29, 30, 31, PPROM compared with that of SPTD. higher rate of BPD, PVL, and NEC in the
32, or 33 weeks), we analyzed the overall Second, prolonged latency (⬎7 days), PPROM group, and the association of a
effect of the duration of the latency pe- oligohydramnios, male fetal sex, nulli- GBS carrier status with adverse neonatal
riod on neonatal outcome (Figure 4). We parity, and a GBS carrier status are asso- outcome in the PPROM group provide
identified a clear trend of decreased rate ciated with increased risk for adverse some support to this hypothesis.
of adverse neonatal outcome with in- neonatal outcome in cases of uncompli- We have also hypothesized that if it is
creasing duration of the latency period, cated PPROM, independently of gesta- the differences in the intrauterine envi-
irrespective of gestational age at presen- tional age. Third, for women with un- ronment that are responsible for the less-
tation with PPROM. Thus, it appears complicated PPROM at gestational age favorable outcome in cases of uncompli-
that for women with uncomplicated 28-33 weeks, the benefit of more ad- cated PPROM, then the duration
PPROM at gestational age 28-33 weeks, vanced fetal maturity associated with ex- through which the fetus is exposed to
the overall effect of expectant manage- pectant management appear to out- this environment (ie, the latency period)
ment is beneficial, despite the potential weigh the potential harming effect of a will affect neonatal outcome. Indeed, we
negative effects associated with pro- prolonged latency period. have found that in cases of uncompli-
longed latency. We were able to identify only 1 study cated PPROM, a prolonged latency pe-
comparing neonatal outcome in cases of riod, for each given gestational age at de-
C OMMENT PPROM with that of neonates following livery, is an independent risk factor for
In the current study we hypothesized SPTD. Newman et al20 compared neona- adverse neonatal outcome (Figures 2 and
that, considering the potential differ- tal outcome in cases of PPROM at gesta- 3). For illustration, in a case of PPROM
ences in the intrauterine environment, tional age of 23-27 weeks with that of at 28 weeks that culminates in delivery at

48.e5 American Journal of Obstetrics & Gynecology JANUARY 2011

www.AJOG.org Obstetrics Research
the more advanced fetal maturity
FIGURE 3
achieved, and a negative effect that may
The effect of the latency period on specific neonatal outcomes
be related to the prolonged fetal expo-
sure to an unfavorable intrauterine envi-
ronment (as described in the preceding
paragraph). To determine whether, at a
certain gestational age, the negative ef-
fects of expectant management outweigh
its beneficial effects, we compared the
outcome of cases of PPROM that oc-
curred in the same gestational week and
were followed by latency periods of dif-
ferent durations (Figure 4). Our results
suggest that for women presenting with
PPROM at gestational age 28-33 weeks,
in the absence of PPROM-related com-
plications (ie, chorioamnionitis, placen-
tal 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 gesta-
tion appears to be associated with less-
Effect of prolonged latency period (⬎7 days; dark bars) on neonatal respiratory, neurologic, and favorable neonatal outcome compared
infectious morbidity in cases of preterm premature rupture of membranes. Data are stratified by with the case that results in delivery at 32
latency period (ⱕ7 [light bars] and ⬎7 days) and gestational age at delivery. weeks of gestation, even though the neo-
*P ⬍ .05. nate in the latter case might have been
Melamed. PPROM and neonatal outcome. Am J Obstet Gynecol 2011. exposed to an unfavorable intrauterine
environment for a longer period of time.
Thus, it can be deduced that these results
32 weeks, neonatal outcome appears to clinical intraamniotic infection as the do not provide support for a practice of
be less favorable than in the case of duration of the latency period increases. immediate delivery in cases of PPROM
PPROM at 31 weeks that also results in Thus, it appears that expectant man- at gestational age of 28-33 weeks. Never-
delivery at 32 weeks of gestation. An- agement in cases of PPROM is associated theless, because of our selective study
other possible explanation for this obser- with 2 opposing effects on neonatal out- population and the retrospective design,
vation is the higher probability for sub- come–a beneficial effect resulting from 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
OR Estimated RR OR Estimated RR
Risk factors (95% CI) (95% CI)b Risk factors (95% CI) (95% CI)b
Nulliparity 3.1 (1.8–5.5) 1.7 (1.4–2.0) Oligohydramnios (AFI ⬍50 mm) 2.5 (1.4–4.5) 1.8 (1.3–2.3)
................................................................................................................................................................................................................................................................................................................................................................................
Oligohydramnios (AFI ⬍50 mm) 2.8 (1.5–5.3) 1.9 (1.3–2.5) Male sex 2.1 (1.6–4.4) 1.4 (1.3–1.8)
................................................................................................................................................................................................................................................................................................................................................................................
GBS carrier 2.7 (1.3–4.8) 2.5 (1.3–4.0) Latency period ⬎7 d 1.9 (1.1–3.3) 1.5 (1.1–1.9)
................................................................................................................................................................................................................................................................................................................................................................................
Latency period ⬎7 d 1.7 (1.1–2.8) 1.4 (1.1–1.8) Gestational wk 0.6 (0.5–0.8) N/A
................................................................................................................................................................................................................................................................................................................................................................................
Male sex 1.7 (1.1–3.2) 1.3 (1.1–1.7)
................................................................................................................................................................................................................................................................................................................................................................................
Gestational wk 0.6 (0.4–0.7) 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 2011.

JANUARY 2011 American Journal of Obstetrics & Gynecology 48.e6

Research Obstetrics www.AJOG.org

the other risk factors for adverse out-

FIGURE 4
come identified in the current study.
Overall effect of duration of latency period on neonatal
Further prospective studies are needed
outcome in cases of expectant management of PPROM
to validate our observations and to
define the reasons for the less-favor-
able neonatal outcome in cases of
PPROM. f

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