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Obstetrics

Correlation of Residual Amniotic Fluid and


Perinatal Outcomes in Periviable Preterm
Premature Rupture of Membranes
Claudine Storness-Bliss, BSc,1 Amy Metcalfe, MSc,2 Rebecca Simrose, MD,3
R. Douglas Wilson, MD,3 Stephanie L. Cooper, MD3
1

Faculty of Medicine, University of Calgary, Calgary AB

Community Health Sciences, University of Calgary, Calgary AB

Department of Obstetrics and Gynecology, University of Calgary, Calgary AB

Abstract

Rsum

Objective: To correlate maternal and fetal outcomes of pregnancies


affected by preterm premature rupture of membranes (PPROM) at
< 24 weeks gestational age with the amount of residual amniotic
fluid as determined by sonographic evaluation.

Objectif: Chercher tablir une corrlation entre les issues


maternelles et ftales de grossesses affectes par la rupture
prmature des membranes prterme (RPMP) un ge
gestationnel < 24semaines et la quantit de liquide amniotique
rsiduel dtermine par valuation chographique.

Methods: We searched the local maternal-fetal medicine database


for the records of all women with PPROM prior to 24 completed
weeks of pregnancy. The quantity of residual amniotic fluid
determined by ultrasound was recorded and women were
separated into two groups: (A) deepest vertical pocket (DVP)
1 cm, or (B) DVP < 1 cm (severe oligohydramnios). Hospital
chart review was undertaken to determine latency to delivery,
perinatal death, and maternal complications. Data were analyzed
using Fisher exact and Wilcoxon-Mann-Whitney U tests.
Results: We identified 31 subjects, of whom nine elected termination
of pregnancy (6 in group A, 3 in group B). Six of 10 subjects in
group A had a live delivery without neonatal death, whereas only
one of 12 subjects in group B had a live delivery (P = 0.020).
Additional complications included placental abruption in 63%
in group A and 45% in group B, chorioamnionitis in 50% and
70%, respectively, and postpartum endometritis in 0% and
9%, respectively. None of these differences were statistically
significant. There were no cases of maternal sepsis or maternal
death in either group. Group A was associated with a later GA
at delivery (27.5 weeks vs. 23 weeks, P = 0.07), with the GA at
rupture of the membranes similar for both groups.
Conclusion: These results indicate that a higher level of residual
amniotic fluid after periviable PPROM is associated with fetal
survival and increased latency to delivery without an increase
in maternal complications. This information will be valuable in
counselling pregnant women with PPROM < 24 weeks.

Key Words: Periviable preterm premature rupture of membranes,


amniotic fluid, perinatal survival
Competing Interests: None declared.
Received on July 21, 2011
Accepted on September 30, 2011

154 l FEBRUARY JOGC FVRIER 2012

Mthodes: Nous avons men des recherches dans la base de


donnes locale de mdecine fto-maternelle afin den tirer
les dossiers de toutes les femmes ayant prsent une RPMP
avant 24semaines compltes de grossesse. La quantit de
liquide amniotique rsiduel dtermine par chographie a t
consigne et les femmes ont t rparties en deux groupes:
(A) poche verticale la plus profonde (PVP) 1cm ou
(B) PVP < 1cm (oligohydramnios grave). Une analyse des
dossiers hospitaliers a t mene afin de dterminer le dlai
avant laccouchement, la prsence dun dcs prinatal et
la survenue de complications maternelles. Les donnes ont
t analyses au moyen du test exact de Fisher et du test de
Wilcoxon-Mann-Whitney U.
Rsultats: Nous avons identifi 31 sujets, neuf desquels ont choisi
linterruption de grossesse (6 du groupe A, 3 du groupe B).
Six sujets du groupe A sur 10 ont donn lieu une naissance
vivante sans dcs nonatal, tandis que cela na t le cas
que chez un sujet du groupe B sur 12 (P = 0,020). Parmi les
complications additionnelles, on trouvait le dcollement placentaire
chez 63% des sujets du groupe A et 45% des sujets du
groupe B, la chorioamnionite (50% et 70%, respectivement) et
lendomtrite postpartum (0% et 9%, respectivement). Aucune
de ces diffrences ne sest avre significative sur le plan clinique.
Aucun cas de septicmie maternelle ou de dcs maternel na t
constat au sein des groupes. Le groupe A a t associ un AG
plus avanc au moment de laccouchement (27,5semaines, par
comp. avec 23semaines, P = 0,07), lAG au moment de la rupture
des membranes tant similaire dans les deux groupes.
Conclusion: Ces rsultats indiquent quun niveau accru de liquide
amniotique rsiduel la suite dune RPMP priviable est associ
la survie ftale et un dlai accru avant laccouchement, sans
augmentation de la frquence des complications maternelles.
Cette information savrera utile dans le cadre du counseling des
femmes enceintes prsentant une RPMP < 24semaines.
J Obstet Gynaecol Can 2012;34(2):154158

Correlation of Residual Amniotic Fluid and Perinatal Outcomes in Periviable Preterm Premature Rupture of Membranes

INTRODUCTION

reterm premature rupture of membranes occurs in


approximately 1% of continuing pregnancies, and,
although associated with perinatal morbidity and mortality,
generally results in good maternal and fetal outcomes.1
Periviable PPROM occurs in 0.4% of continuing
pregnancies, and is defined as rupture of membranes prior
to the age of fetal viability, but after most spontaneous
abortions have occurred (14 to 24 gestational weeks).2
Perinatal outcomes in these cases have been reported as
poor, mainly due to secondary deformational pulmonary
hypoplasia, although neurological complications, infection,
and congenital malformations have also been described.2,3
Furthermore, maternal health following periviable PPROM
may be compromised due to the risks of chorioamnionitis,
sepsis, placental abruption, and complications of
immobility.4
Many factors are important when counselling the pregnant
patient with periviable PPROM, including gestational age,
latency to delivery, and risks of expectant management,
given the high rate of associated complications. Data on
maternal/neonatal morbidity, fetal/neonatal mortality, and
fetal treatment are limited, because studies are generally
small and differ in their inclusion and exclusion criteria.
Dewan and Morris, in a systematic review of PPROM
<23 weeks between the years 1980 to 1994, reported a
20% perinatal survival rate.5 Although neonatal care has
advanced, periviable PPROM has typically been associated
with a very poor prognosis, and many patients are
counselled to consider termination of pregnancy.
More recently, advances in both antenatal and neonatal
care (including antenatal corticosteroid use, antibiotic
use, use of postnatal surfactant, and neonatal gentle
ventilation strategies) have allowed the definition of fetal
viability to be revisited and the outcome for periviable
PPROM to be questioned.28 Everest et al. reported a
55.7% survival rate after conservative management of
periviable PPROM.6
To counsel patients in the setting of periviable PPROM
appropriately, it is essential to present the best available
options, including the risks and potential complications,
using pertinent and centre-based outcome data. Fifty
percent of pregnancies complicated by periviable PPROM
deliver within seven days, with the majority delivering

ABBREVIATIONS
DVP

deepest vertical pocket

PPROM preterm premature rupture of membranes

within 48 hours.4 Therefore, cases that do not present with


imminent labour or signs of chorioamnionitis require those
involved to make the difficult decision either to pursue
expectant management or to terminate the pregnancy.
One clinical variable which may assist in the counselling
of these patients is the residual amniotic fluid volume as
determined by ultrasound. Hadi et al., in a prospective
cohort of 178 singleton pregnancies complicated by
PPROM at 20 to 25 weeks gestational age, found that the
presence or absence of amniotic fluid was associated with
latency to labour.9 However, their study excluded PPROM
before 20 weeks gestation, included amniotic fluid levels
measured throughout pregnancy, and excluded all cases
with latency to labour of less than seven days. They found
that the frequency of chorioamnionitis was higher (33.8%
vs. 21.5%, P = 0.07) and perinatal survival was lower
(9.9% vs. 85%, P <0.01) in patients with oligohydramnios
(defined as ultrasonographic measurement of the deepest
vertical pocket of amniotic fluid as <2cm) than in
patients without oligohydramnios. Kilbride et al. compared
survivors and non-survivors following periviable PPROM.3
They found that non-survivors, in addition to being
less mature than survivors, having a longer duration of
PPROM, and lower birth weights, were more likely to have
severe oligohydramnios, defined as < 1 cm vertical pocket
on ultrasonographic measurement of amniotic fluid.
The finding of improved outcomes with higher levels of
amniotic fluid has been confirmed in women with PPROM
at later gestations as well.10
The primary objective of this study was to correlate both
the average latency to delivery at the time of PPROM and
perinatal mortality (fetal death or neonatal death within
30 days of life) with the level of residual amniotic fluid,
as measured by 2-D ultrasound. Secondary outcomes
included the incidence of chorioamnionitis, placental
abruption, postpartum endometritis, retained placenta,
maternal sepsis, and death in cases of periviable PPROM.
METHODS

We evaluated the outcomes of singleton pregnancies


with rupture of membranes prior to 24 weeks of
gestation and with a minimal latency to delivery of
48 hours, occurring between January 1, 2002, and
January 15, 2011, in a retrospective cohort study.
Gestational age was determined by last menstrual
period and confirmed when possible by first trimester
ultrasound. Rupture of membranes was diagnosed by
clinical history in combination with a sterile speculum
examination demonstrating vaginal pooling of amniotic
FEBRUARY JOGC FVRIER 2012 l 155

Obstetrics

categorical variables and the Wilcoxon rank sum test for


continuous variables. Because of the small sample size
and descriptive nature, P<0.10 was deemed statistically
significant.

Table 1. Subject demographics by group


Parameter

DVP
< 1 cm

DVP
1 cm

18

13

Number
Terminations

06

03

Expectant management

12

10

This study was approved by the Conjoint Health Research


Ethics Board at the University of Calgary.
RESULTS

Table 2. Primary endpoints


Primary endpoints
Latency, days
Perinatal survival, n (%)

Both
groups

DVP
< 1 cm

DVP
1 cm

18

13

57

0.014

7 (31.8)

1 (8.3)

6 (60)

0.02

Table 3. Maternal complications


DVP
< 1 cm, %

DVP
1 cm, %

Chorioamnionitis

70

50

0.63

Endometritis

09

00

N/A

Placental abruption

45

63

0.65

Retained placenta

20

22

> 0.99

Complication

fluid and microscopic identification of a ferning pattern.


Subjects who presented with chorioamnionitis (fever,
abdominal pain, and fetal tachycardia), fetal demise, or
active labour (uterine contractions with cervical dilatation)
at the time of PPROM were excluded from the study.
Multiple gestations, PPROM following amniocentesis or
chorionic villus sampling, or any pregnancies with a preexisting diagnosis of major congenital or chromosomal
abnormalities were also excluded.
Patients with PPROM were referred to the Southern
Alberta Centre for Maternal-Fetal Medicine for evaluation
and counselling. The local maternalfetal medicine
electronic database was searched to retrieve the records
of PPROM cases and to review sonographic findings
including residual amniotic fluid volume. Cases were
separated into two groups:
A residual amniotic fluid demonstrating a deepest
vertical pocket 1cm, and
B residual amniotic fluid DVP <1cm (severe
oligohydramnios).
Perinatal and maternal outcomes were determined from
manual chart review at the delivery hospital. Bivariate
associations were assessed using the Fisher exact test for
156 l FEBRUARY JOGC FVRIER 2012

A total of 31 pregnancies met the inclusion criteria


for evaluation. Following sonographic evaluation
and counselling, nine subjects elected for pregnancy
termination, six in the DVP < 1 cm group and three in the
DVP 1cm group (Table1). For analysis of subjects who
followed expectant management, there were 12 patients in
the DVP <1cm group and 10 in the DVP 1cm group.
The primary endpoints of this study are summarized in
Table 2. There were statistically significant differences both
in latency to delivery and in perinatal mortality between the
two groups. The overall survival rate was 31.8% and mean
latency to delivery was 43 days. Mean latency to delivery
in the DVP <1cm group was 32 days, in contrast to
57 days in the DVP 1cm group (P=0.014). Furthermore, survival was more than seven-fold increased in the
DVP 1cm group over the DVP <1cm group (60% vs.
8.3 %, P = 0.02).
The mean gestational age at the time of rupture of
membranes was 18.5 weeks and at the time of delivery was
25 weeks. The mean gestational age at rupture of membranes
and at time of delivery for both groups is shown in the
Figure. There was no significant difference in gestational
age at rupture of membranes between the DVP < 1 cm
and DVP 1 cm groups (18 and 19 weeks respectively).
However, gestational age at time of delivery was, on average,
4.5 weeks later in the DVP 1cm group than in the DVP
<1cm group (27.5 weeks vs. 22.9 weeks, P=0.07).
Perinatal complications were assessed (Table3). Seventy
percent of patients in the DVP <1cm group and 50%
of patients in the DVP 1cm group experienced
chorioamnionitis. Similarly, 9% of patients in the DVP
<1cm group had postpartum endometritis, but none of
the patients in the DVP 1cm group did. These differences
were not statistically significant. Placental abruption occurred
in 45% of the DVP <1cm group and in 63% of the DVP
1cm group. Rates of retained placenta were similar in
the two groups (20% and 22%, respectively). There were
no cases of maternal sepsis or death recorded during the
study. Overall, there were no statistical differences between
the two groups with regard to maternal complications.

Correlation of Residual Amniotic Fluid and Perinatal Outcomes in Periviable Preterm Premature Rupture of Membranes

DISCUSSION

The clinical scenario of periviable PPROM is challenging


for both patient and clinician. In the absence of
chorioamnionitis or active labour, the decision to
pursue expectant management must be based on careful
consideration of maternal/fetal risks and pregnancy
outcomes in the setting of limited published data. Our
sample size was limited by numerous factors: periviable
PPROM is extremely rare, a number of patients either
develop chorioamnionitis or progress to active labour, and
strict inclusion criteria were used. In an effort to obtain
consistent data, cases of multiple gestation, fetal demise,
and congenital or chromosomal anomalies, and cases
that progressed to active labour within 48 hours were
excluded. Nonetheless, the survival rate in the present
cohort was higher than previously described.5 This may
reflect heterogeneity between patient groups in prior
studies. Similarly, cases of iatrogenic PPROM following
amniocentesis or chorionic villus sampling were excluded,
because these cases typically have better outcomes.11
The present findings agreed with those of Hadi
et al.,9 in that there was a significant difference in latency
to delivery and perinatal survival between cases with
severe oligohydramnios and those without. In contrast
to the study of Hadi et al., our study included only the
initial residual amniotic fluid measurements after early
PPROM, as opposed to a mean of all amniotic fluid level
measurements throughout pregnancy. This is an important
difference as patients may benefit from timely information
regarding the prognosis of their pregnancy.
As there was no difference in GA at onset of membrane
rupture between the two groups in the present study,
survival may be attributed to increased latency to labour
resulting in later GA at delivery. Importantly, enhanced
latency to delivery was achieved without increasing the
incidence of maternal complications. Alternatively, as
amniotic fluid is important for pulmonary development in
mid-pregnancy, improved perinatal survival in the absence
of severe oligohydramnios may be a direct consequence
of the impact of residual amniotic fluid volume on lung
development and subsequent postnatal lung function.
Physiologically, factors that may contribute to pulmonary
hypoplasia due to severe olighydramnios include fetal
thoracic compression, restriction of fetal breathing, and
disturbances of pulmonary fluid and flow.12
There are a number of therapies that have been proposed
for the management of periviable PPROM, including
amnioinfusion and artificial sealing of the membranes.13
However, the efficacy and safety of these treatments

Gestational age at rupture of membranes and at


delivery
40

P = 0.07

30

20

10

0
GA at ROM

DVP < 1 cm

GA at delivery

DVP

1 cm

have not been adequately studied, and additional research


evaluating these strategies should be undertaken.
In animal models, labour can be induced by infusion of
adrenocorticotropic hormone or cortisol.12 This mechanism
does not appear to be directly responsible for triggering
onset of parturition in humans and higher primates.12 We
can hypothesize that in periviable PPROM, oligohydramnios
could contribute to severe fetal stress, accompanied by an
immense rise in fetal cortisol levels. In such a situation, it is
possible that the maternal-fetal response to PPROM could
revert to a less advanced mechanism, in evolutionary terms,
for the onset of labour. If a higher level of residual amniotic
fluid is associated with less thoracic compression and fewer
disturbances of pulmonary fluid and flow, it could create
a reduction in biological stress, resulting in an increased
latency to the onset of labour.
CONCLUSION

Choosing the appropriate management of periviable


PPROM with respect to the level of amniotic fluid,
pulmonary hypoplasia, latency to delivery, and survival is
difficult. Our study shows an association between higher
levels of residual amniotic fluid after PPROM and overall
outcomes, but it is not possible to confirm the etiology of
this association. A prospective study, including childhood
outcomes, is the next logical step in establishing guidelines
for the management of periviable PPROM. Further
studies to validate the present findings are warranted. In
the interim, routine evaluation of the residual amniotic
fluid should be considered when counselling pregnant
women with periviable PPROM.
FEBRUARY JOGC FVRIER 2012 l 157

Obstetrics

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