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Arch Gynecol Obstet (2009) 280:711

DOI 10.1007/s00404-008-0836-8

O R I G I N A L A R T I CL E

Neonatal outcome in preterm deliveries between 23 and 27


weeks gestation with and without preterm premature rupture
of membranes
Dana E. Newman Orit Paamoni-Keren
Fernanda Press Arnon Wiznitzer
Moshe Mazor Eyal Sheiner

Received: 29 August 2008 / Accepted: 28 October 2008 / Published online: 25 November 2008
Springer-Verlag 2008

Abstract
Objectives To characterize neonatal morbidity and mortality rates in extreme preterm deliveries (between 23 and
27 weeks gestation) with and without PPROM, and to
evaluate the association between PPROM and chorioamnionitis.
Methods A retrospective population-based study was
conducted on preterm singleton pregnancies delivered
between 23 and 27 weeks gestation from 1988 to 2007.
Immediate neonatal morbidity and mortality rates in pregnancies complicated by PPROM were compared to pregnancies with intact membranes. A multivariate analysis was
conducted in order to determine the independent association between PPROM and chorioamnionitis.
Results Out of 1,437 preterm deliveries, 236 (16.4%)
were complicated with PPROM. There were more neonates
with low 1 min (61.0 vs. 42.5%; P = 0.001) and low 5 min
(30.1 vs. 23.8%; P = 0.042) Apgar scores (of less than 7) in
pregnancies complicated by PPROM than in the comparison group. There were more cases of chorioamnionitis in
the PPROM group born at 2324 weeks gestation (33.8 vs.
17.0%; P < 0.001), and in the PPROM group born at 25
27 weeks (42.0 vs. 15.5%; P < 0.001). In the group born at
2324 weeks gestation, there were more postpartum
deaths (PPD) in the PPROM group (70.0 vs. 54.8%;
P = 0.013); however, there was no signiWcant diVerence in
PPD in the groups born at 2527 weeks. In the group born

D. E. Newman O. Paamoni-Keren F. Press A. Wiznitzer


M. Mazor E. Sheiner (&)
Department of Obstetrics and Gynecology,
Faculty of Health Sciences, Soroka University Medical Center,
Ben Gurion University of the Negev, P.O. Box 151,
Beer Sheva, Israel
e-mail: sheiner@bgu.ac.il

at 2324 weeks, as well as at 2527 weeks, there were


fewer antepartum deaths (APD) in the PPROM group as
compared to the control group (16.3 vs. 32.6%; P = 0.002,
and 5.3 vs. 36.3%; P < 0.001; respectively). After adjusting
for gestational age and gender, using a multivariate analysis,
the association between PPROM and chorioamnionitis
remained signiWcant (OR = 3.32; 95% CI 2.434.51,
P < 0.001).
Conclusions PPROM is associated with adverse perinatal
outcome in deliveries between 23 and 27 weeks gestation.
Moreover, PPROM is an independent risk factor for chorioamnionitis.
Keywords Preterm premature rupture of membranes
Chorioamnionitis Preterm delivery

Introduction
Preterm premature rupture of membranes (PPROM) refers
to rupture of the amniotic membranes before 37 weeks of
gestation and prior to the onset of labor. The incidence of
PPROM is 23% in all pregnancies, and constitutes 30
40% of preterm deliveries [1]. Preterm labor and PPROM
results from pathological signaling and activation of the
parturition common pathway [2]. Known risk factors for
PPROM include previous PPROM pregnancy, multiple
gestation, smoking, African American ethnicity [3], lower
socioeconomic class [4], infection [5], trauma, incompetent
cervix, placental abruption, genetic and enzymatic abnormalities, and nutritional deWciencies [1]. PPROM is associated with considerable fetal, neonatal, and maternal risk.
Immediate complications include chorioamnionitis, placental
abruption, prolapsed cord, preterm labor and delivery, neonatal sepsis, intraventricular hemorrhage, and necrotising

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enterocolitis. Long-term eVects include pulmonary hypoplasia, respiratory distress syndrome, cerebral palsy, fetal
compression syndrome, and fetal death [69].
Ramsay et al. compared morbidities of neonates born
between 24 and 37 weeks gestation, whose mothers developed chorioamnionitis after PPROM, to those whose mothers
did not develop chorioamnionitis [6]. Their study revealed a
signiWcantly higher composite major morbidity rate in neonates who were exposed to intrauterine infection versus those
who were not (55.4 vs. 18.2%; P < 0.0001). They also
reported that the group with chorioamnionitis had younger
gestational age at PPROM (P < 0.0001), longer latency
(P < 0.0003), younger gestational age at delivery (P <
0.0001), lower birth-weight (P < 0.0001) as well as lower
1 min (P = 0.001) and 5 min (P = 0.002) Apgar scores [7].
There is still limited consensus regarding the approach to
PPROM [10]. The controversy surrounds the issue of
expectant management versus expeditious delivery [11]. At
Soroka University Medical Center, PPROM is managed
expectantly. This implies hospitalization, complete bed
rest, avoidance of digital pelvic exam, as well as administration of corticosteroid and antibiotic prophylaxis [12, 13].
Contractions and fetal heart rate are monitored regularly,
and immediate delivery is performed if there are any signs
of infection, fetal distress, cord compression, or abruption.
Some cases undergo amniocentesis to exclude intraamniotic infection. There is a paucity of research regarding the
optimal treatment of a woman who undergoes conservative
management of PPROM from when the fetus is barely viable, to when it reaches advanced gestational age [12]. In the
absence of labor, abruption, non-reassuring fetal testing, or
chorioamnionitis, labor may be induced at 3234 weeks
gestation, if there is documented fetal lung maturity [12].

Materials and methods


After obtaining institutional review board approval, we conducted a Wle search for a cohort of patients between 1988 and
2007, with preterm deliveries at 2327 weeks gestation. The
group was sub-divided into 2324 weeks, and 25 weeks and
above since babies born at 2324 weeks gestation (unlike 25
and above) are not actively resuscitated. Only spontaneous
(non-induced) preterm deliveries were included in the study.
Excluded from the study were cases with multifetal pregnancy, fetal anomalies, and hypertensive disorders.
Data were collected from the perinatal database that contains information recorded by an obstetrician, immediately
after delivery. Skilled medical secretaries routinely check the
information before it is entered into the database. Coding is
performed after assessment of medical prenatal care records
as well as standard hospital documents. These procedures
assure maximal completeness and accuracy of the database.

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Arch Gynecol Obstet (2009) 280:711

The following demographic and clinical characteristics


were investigated: presence of PPROM, presence of chorioamnionitis, 1 and 5 min Apgar scores of less than 7, gestational age at delivery, birth weight, gender of the baby, and
perinatal mortality. Gestational age was determined from
the date of last menstrual period (if reliable), or by ultrasound. Chorioamnionitis was deWned clinically, as the presence of uterine tenderness and/or purulent or malodorous
amniotic Xuid with any two of the following: antepartum
temperature of more than 37.8C (100.4F), maternal
tachycardia (>120 beats/min), maternal leucocytosis
(>18,000 cells/mm3), or fetal tachycardia (>160 beats/min)
[7]. Women with PPROM were managed expectantly, with
hospitalization and complete bed rest. They received Betamethasone and prophylactic Ampicillin and Erythromycin,
and were followed for signs of infection, abruption, and
fetal well-being, using the biophysical proWle and nonstress test. The control group, i.e. the no PPROM group,
received the same standard of care treatment, including steroids for lung maturity.
Statistical analysis was performed with the SPSS package (SPSS, Chicago, IL). Statistical signiWcance was calculated using the chi square test, or Fishers exact test for
diVerences in qualitative variables. A multivariate logistic
regression model, with backward elimination, was constructed in order to Wnd independent risk factors associated
with maternal chorioamnionitis. P value <0.05 was determined to be statistically signiWcant.

Results
Of the total 1,437 preterm deliveries, 236 (16.4%) had
PPROM, 768 babies (53.4%) were born at 2324 weeks
gestation, and 669 (46.6%) babies were born at 2527
weeks gestation. Of the 1,437 deliveries, 275 (19.1%) had
chorioamnionitis. In the group born at 2324 weeks gestation, there were more cases of chorioamnionitis in the
PPROM pregnancies (33.8 vs. 17%, P < 0.001); similarly
in the group born at 2527 weeks gestation, there were
more cases of chorioamnionitis in the PPROM group (42
vs. 15.5%, P < 0.001). The PPROM group had more cases
of low 1 min (P = 0.001) and 5 min (P = 0.042) Apgar
scores than the non-PPROM group. No signiWcant diVerence was found with gestational age (P = 0.091) or gestational weight (P = 0.439) in the PPROM group (Table 1).
The PPROM group born at 2324 weeks gestation had
fewer antepartum deaths than the control group (16.3 vs.
32.6%; P = 0.002), as did the PPROM group born at 25
27 weeks gestation (5.3 vs. 36.3%; P < 0.001). Nevertheless, the PPROM group delivered at 2324 weeks had
more postpartum deaths (70.0 vs. 54.8%; P = 0.013)
(Tables 2, 3).

Arch Gynecol Obstet (2009) 280:711


Table 1 Clinical characteristics
of pregnancies with and without
preterm premature rupture of
membranes (PPROM)

PPROM
(n = 236)

Intact membranes
(n = 1,201)

P value

1 min Apgar score < 7

61.0 %

42.5 %

<0.001

5 min Apgar score < 7

30.1 %

23.8 %

Chorioamnionitis 2324 weeks

33.8%

17%

<0.001

Chorioamnionitis 2527 weeks

42.0%

15.5%

<0.001

Cesarean delivery

50.8%

45.0%

0.113

Gestational age at delivery in weeks (mean SD)

24.5 4

24.1 5

0.091

Birth-weight in g (mean SD)

814.2 319.8

844.8 589.5

0.439

Table 2 Perinatal mortality in deliveries at 2324 weeks gestation


PPROM
(n = 110)

Intact membranes
(n = 658)

P value

Antepartum death

16.3%

32.6%

0.002

Intrapartum death

12.5%

7.3%

0.175

Postpartum death

70.0%

54.8%

0.013

Table 3 Perinatal mortality in deliveries at 2527 weeks gestation


PPROM
(n = 126)

Intact membranes
(n = 543)

P value

Antepartum death

5.3%

36.3%

<0.001

Intrapartum death

3.3%

2.6%

0.585

Postpartum death

28.0%

30.1%

0.343

Table 4 Independent risk factors associated with chorioamnionitis


(CI = conWdence interval; OR = odds ratio)
Risk Factor

OR

95% CI

P value
<0.001

PPROM

3.32

(2.434.51)

Male gender

2.58

(0.23128.79)

0.442

Gestational age (days)

1.01

(1.0031.01)

0.004

Controlling for gestational age and gender, the multivariate analysis revealed a signiWcant independent association
between PPROM and chorioamnionitis (OR = 3.32; 95%
CI 2.434.51, P < 0.001). A signiWcant association also
remained between gestational age and chorioamnionitis
(OR = 1.01; 95% CI 1.0031.01, P = 0.004), meaning that
in this group of patients there is a 1.01 times increase in
exposure to chorioamnionitis per day in utero (Table 4).

Discussion
Most studies on PPROM management include all preterm
deliveries, from vulnerable 24-week-old fetuses, to relatively robust 36-week-olds. Furthermore, deliveries at less
than 28 weeks are usually grouped together and labeled

0.042

remote from term. This study is unique because it


addresses the most vulnerable subset (2327 weeks gestation) of a population that is already at risk.
Our research showed that PPROM pregnancies delivered
at 2327 weeks of gestation were associated with lower
Apgar scores and more chorioamnionitis. After adjusting
for gestational age and gender, PPROM remained an independent risk factor associated with chorioamnionitis.
Indeed, such an association was noted previously [14].
Tanir et al. [15] compared preterm deliveries prior to
34 weeks of gestation, with and without PPROM, and
reported the following independent risk factors for chorioamnionitis: gestational age at delivery (P = 0.009), 1 min
Apgar (P = 0.013), and umbilical artery pH (P = 0.046).
They found no signiWcant diVerence in neonatal mortality
between the groups; however, they recognized that the
major factor in determining neonatal outcome is gestational
age itself. Likewise, another retrospective study noted that
PPROM is associated with lower gestational age (24
32 weeks) and birth weight <2,500 g [14]. On the contrary,
the present study did not Wnd a signiWcant diVerence in
birth weight.
For each day a preterm fetus stays in utero with premature ruptured membranes, it is 1.011 times more likely to be
exposed to chorioamnionitis. Intrauterine infection is associated with complications such as intraventricular hemorrhage, bronchopulmonary dysplasia, cerebral palsy,
periventricular leukomalacia, and neonatal death [7]. Moreover, PPROM may cause oligohydramnios, which may lead
to pulmonary hypoplasia after a period as short as 6 days
[16]. This presents the obvious dilemma of how long to
continue expectant management in PPROM; increased gestational age allows for fetal lung maturity; however, there is
a concomitant increased risk of maternal infection, placental abruption, postpartum hemorrhage, and neonatal sepsis.
Our study did not have the opportunity to determine latency
period; however, future studies could calculate the optimal
length of latency for reducing the incidence of chorioamnionitis.
Perinatal mortality rates were high in both the PPROM
and the intact membranes group born at 2324 weeks (98.8

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10

vs. 94.7%), which corresponds with Mercers review [12].


Previous study [14] reported higher total perinatal mortality
rates in the group without PPROM (10.5 vs. 7.2%;
P = 0.01); however, the PPROM group had more postpartum deaths (5.5 vs. 4%; P < 0.01). In our study, the
PPROM group delivered at 2327 weeks had surprisingly
fewer APD than the control. Unfortunately, we do not have
data regarding resuscitative measures of the neonates or
their speciWc causes of death. The high stillbirth rates in the
control group may be caused by increased frequency of
umbilical cord compression, hypoxia, or chorioamnionitis.
There is also the unwritten practice of non-intervention for
non-reassuring fetal heart rate monitoring in the periviable
fetus [12]. There was no signiWcant diVerence in intrapartum death (IPD) between the two groups. Regarding postpartum deaths (PPD), there were more cases in the PPROM
group born at 2324 weeks than the no PPROM group;
however, the rates in both groups were quite high (70.0 vs.
54.8%; P < 0.013). In the PPROM group born at 25
27 weeks, there was no signiWcant diVerence in postpartum
deaths compared to the control. The increased postpartum
mortality at a younger gestational age may be attributed to
intraventricular hemorrhage, necrotizing enterocolitis, cord
accident, abruption, and especially respiratory distress syndrome (RDS). In the 2324 weeks group, the overall mortality rate was 9498%. The presence or absence of
PPROM was not a clinically signiWcant factor here, as the
main determinant of perinatal death must be gestational
age. It is not clear why in the 2527 weeks group, the overall perinatal mortality in the non-PPROM group was 69
versus 36.6% in the PPROM group. Most perinatal mortality cases were attributed to prematurity, while the rate of
abruption, which was previously shown to be higher in preterm deliveries [17], did not diVer between the two groups
(6.1 vs. 5.1%). Jahromi et al. [6] showed that in PPROM
pregnancies that were delivered between 24 and 37 weeks
gestation, the risk of RDS decreases linearly when the duration of PPROM is prolonged in the Wrst 48 h; this allows for
the administration of antibiotic and surfactant therapy.
When latency exceeds 48 h, however, outcomes become
less clear due to increased risk of sepsis and chorioamnionitis. Unfortunately, Jahromi et al. grouped together all deliveries before 28 weeks gestation. They also grouped
together all cases of PPROM which lasted more than 48 h.
Pasquier et al. [18] correctly criticize most studies for
focusing on preterm birth after PPROM, rather than starting
from the actual event of rupture of membranes. Women are
therefore counseled about their babys outcome using data
about gestational age at birth, as opposed to gestational age
at PPROM.
In addition to the immediate adverse neonatal outcomes
discussed previously, the survivors of remote-from-term
PPROM deliveries face serious long-term sequelae, includ-

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Arch Gynecol Obstet (2009) 280:711

ing chronic lung disease, cerebral palsy, mental retardation,


hearing loss, retinopathy of prematurity, and motor dysfunction. Not surprisingly, the issue of PPROM management in such preterm pregnancies has sparked an ethical
debate. Considering the high neonatal morbidity and mortality, decreased quality of life, emotional impact on parents, and associated Wnancial costs to the health care
system, some question if delivery is justiWable. Expectant
parents presenting with early PPROM need to be informed
about the risks and beneWts of immediate delivery versus
conservative management. Mercer reminds clinicians that
counseling should include a realistic appraisal of neonatal
outcomes, including the availability of obstetric monitoring
and neonatal intensive care facilities [12]. Pasquier et al.
[18] recommend special follow-up and recurrence risk
assessment for women with a history of PPROM.
In conclusion, remote-from-term PPROM pregnancies
can be traumatic for expectant parents, and nerve-racking
for obstetricians. PPROM is associated with poor neonatal
outcome, including low Apgar scores and chorioamnionitis.
Our study has several limitations. Its retrospective nature
(over a period of almost 20 years) precluded the examination of latency period, as well as comparison of several
treatment protocols. Future studies should compare treatment options, and evaluate the optimal length of latency for
reducing the incidence of chorioamnionitis. In addition,
future studies should categorize perinatal mortality further,
to diVerentiate between the causes of death (APD vs. IPD
vs. PPD) in this speciWc age group.
ConXict of interest statement

None.

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