Keywords
preterm premature rupture of membranes - latent period - chorioamnionitis - respiratory
distress syndrome
Introduction
Premature rupture of membranes (PROM) refers to the loss of amniotic fluid due to
damage to the chorioamniotic membranes surrounding the fetus prior to the onset of
labor. Preterm PROM (PPROM) is defined as membrane rupture occurring before 37 weeks
of gestation and is observed in approximately 3% of all pregnancies. It occurs in
approximately 0.5% of pregnancies before 27 weeks, 1% between 27 and 34 weeks, and
1% between 34 and 37 weeks of gestation.[1]
[2]
Although the exact etiopathogenesis of preterm PROM is not fully understood, several
potential mechanisms have been proposed. The structural integrity of the fetal membranes
relies on extracellular matrix proteins such as collagen, fibronectin, and laminin.
Matrix metalloproteinases (MMPs) contribute to membrane weakening by promoting collagen
degradation.[3] Tissue inhibitors of metalloproteinases bind to MMPs and suppress MMP-mediated proteolysis,
thereby supporting membrane stability.[4] Intra-amniotic infection, particularly during early pregnancy, has been associated
with an increased risk of PPROM.
A previous history of PPROM is one of the most significant factors contributing to
the risk of recurrence in future pregnancies. Additionally, factors such as vaginal
bleeding in the second or third trimester, low body mass index (BMI), short cervical
length, low socioeconomic status, drug use, and smoking can also increase the risk
of PPROM.[5] These factors compromise the integrity of the fetal membranes, increasing the likelihood
of premature rupture. Fetuses exposed to PPROM are at risk for pulmonary hypoplasia,
limb deformities, prematurity, and intrauterine fetal death. Moreover, obstetric complications
such as placental abruption, umbilical cord prolapse, and intrauterine infection can
adversely affect both maternal and neonatal outcomes.[6] Therefore, timely diagnosis and evidence based treatment approaches are crucial
for optimizing maternal and neonatal health outcomes.
This study included patients who experienced membrane rupture between 22 and 26 weeks
of gestation and were delivered at our clinic between 2017 and 2021. Understanding
the factors that influence the duration of the latent period is crucial, as this period
directly affects neonatal survival during the periviable stage. Identifying these
factors can guide clinical decision making and optimize management strategies, thereby
improving both maternal and neonatal outcomes. Therefore, the aim of this study is
to identify key determinants of the latent period, provide evidence supporting personalized
treatment strategies, and contribute to improving the prognosis of both mothers and
neonates.
Methods
This retrospective cohort study included data from 135 pregnant women who presented
to the gynecology and obstetrics clinic of our hospital between 2017 and 2021 due
to preterm membrane rupture between 22 and 26 weeks of gestation, and subsequently
delivered at our institution. The study was approved by the Ethics Committee of İzmir
Tepecik Training and Research Hospital (Approval No: 2021/10–29). A total of 29 patients
were excluded due to multiple fetal anomalies, voluntary discharge, or incomplete
data, resulting in a final cohort of 106 participants.
Inclusion criteria were: a confirmed diagnosis of PPROM between 22 and 26 weeks of
gestation, delivery at our clinic, and complete medical records. Patients were excluded
if they had an uncertain PPROM diagnosis, threatened miscarriage without membrane
rupture, or fetal anomalies. All patients received inpatient management throughout
the latency period. Diagnosis of PPROM was confirmed via sterile speculum examination,
observing amniotic fluid leakage from the cervix or pooling in the posterior fornix.
In uncertain cases, placental α-microglobulin-1 testing (AmniSure) was used. Antibiotic
therapy was initiated immediately, consisting of intravenous ampicillin 1000 mg/sulbactam
500 mg two or three times daily for 10 days, and a single oral dose of azithromycin
1000 mg.
Delivery was indicated in cases of fetal demise, spontaneous labor, or clinical chorioamnionitis,
which was defined by maternal symptoms including fever, uterine tenderness, tachycardia,
or foul smelling vaginal discharge. Laboratory markers such as elevated white blood
cell count or C-reactive protein (CRP) levels were noted but not required.
In accordance with current guidelines, tocolytics were not administered in the presence
of fetal anomalies incompatible with life, intrauterine fetal demise, suspected chorioamnionitis,
or nonreassuring fetal status. Tocolysis was considered in cases without maternal
infection and with favorable fetal maternal evaluation, primarily to allow time for
antenatal corticosteroid administration. Tocolytic treatment was administered solely
to enhance the effectiveness of antenatal corticosteroids and was limited to a maximum
duration of 48 hours. Magnesium sulfate (MgSO4) was administered when delivery was anticipated before 32 weeks of gestation. Betamethasone
was administered intramuscularly in two doses of 12 mg given 24 hours apart (totaling
24 mg). Each dose consisted of 2 mL of a solution containing 3 mg of betamethasone
acetate and betamethasone sodium phosphate equivalent to 3 mg of betamethasone. Tocolysis
was provided using either indomethacin, initiated with a 100 mg rectal loading dose
followed by a maintenance dose of 25 mg orally every 6 hours, or alternatively nifedipine,
administered as a loading dose of 10 mg orally three times at 20 minute intervals,
followed by a maintenance dose of 10 mg orally every 6 hours.
Data were retrospectively collected from hospital records and the electronic database.
Maternal parameters included: age, gravidity, BMI, parity, comorbidities, surgical
history, gestational age at admission, CRP, amniotic fluid volume, urinary tract infection
(UTI) status, hemogram at admission and delivery, and timing of delivery. Fetal data
included: presentation, birth weight, APGAR (Appearance, Pulse, Grimace, Activity,
and Respiration) scores at 1 and 5 minutes, mode of delivery, and indications for
cesarean delivery, if applicable. Administration of magnesium, steroids, tocolytics,
and antibiotics was also documented.
Statistical analyses were performed using IBM SPSS Statistics V25 (IBM Corp., Armonk,
New York, United States). Descriptive statistics were reported as counts (n), percentages (%), means ± standard deviations (x ± SDs), medians (M), and interquartile ranges (IQRs; Q1–Q3). Shapiro–Wilk test and Q–Q plots were used
to assess normality; Levene's test evaluated variance homogeneity. For comparing continuous
variables, independent two-sample t-tests or Mann–Whitney U tests were used as appropriate. Fisher's exact chi-square test was applied for categorical
comparisons. For multiple comparisons, Bonferroni correction was employed. A p-value of < 0.05 was considered statistically significant.
Result
In the study population (n = 106), the mean age was 29.6 ± 7.2 years (range: 15–45), and the median parity
was 1.0 with an IQR of 0.0 to 2.0. The average gestational age at the time of PPROM
diagnosis was 24.2 weeks (± 2.4), and the mean gestational age at delivery was 26.5
weeks (± 2.8). The mean amniotic fluid index (AFI) measured via ultrasonography was
44.1 mm (± 43.5). Neonatal outcomes included a mean birth weight of 985.8 g (± 414.7),
an APGAR score of 4.2 (± 2.07), a blood gas pH of 7.1 (± 0.1), and a mean neonatal
intensive care unit stay of 72.5 days (± 34.1) ([Table 1]).
Table 1
Demographic and clinical characteristics of the study group
|
N
|
Mean ± SD (min-max)
|
|
Age (y)
|
106
|
29.60 ± 7.2 (15–45)
|
|
Body mass index (kg/m2)
|
106
|
30.6 ± 3.38 (20.8–40.27)
|
|
Parity (median)
|
106
|
1.0 (IQR: 0.0–2.0)
|
|
Abortion
|
106
|
0.54 ± 1.09 (0–7)
|
|
Preterm membrane rupture week
|
106
|
24.2 ± 2.4 (13–26)
|
|
Birth week
|
106
|
26.5 ± 2.8 (22–34)
|
|
Latent period duration (d)
|
106
|
15.7 ± 17.6(0–93)
|
|
Amniotic fluid index (mm)
|
106
|
44.1 ± 43.5 (0–120)
|
|
Birth weight (g)
|
106
|
985.8 ± 414.7 (330–2005)
|
|
APGAR score
|
106
|
4.2 ± 2.07 (0–7)
|
|
Fetal cord pH
|
51
|
7.1 ± 0.10(6.9–7.39)
|
|
Neonatal intensive care unit stay (d)
|
31
|
72.5 ± 34.1 (15–159)
|
Abbreviations: APGAR, Appearance, Pulse, Grimace, Activity, and Respiration; IQR,
interquartile range; SD, standard deviation.
Among the 106 pregnant women, 24 delivered vaginally, while 74 underwent cesarean
section (C/S). Of those who delivered by cesarean, 17 cases (23%) were complicated
by chorioamnionitis. Although chorioamnionitis does not constitute an absolute indication
for cesarean delivery, it was present in nearly one-quarter of the cesarean cases.
A prior cesarean delivery during labor accounted for 11 cases (14.9%), while the least
frequent indication was placenta previa (2 cases, 2.7%).
When evaluating the association between BMI and latent period duration, the mean latency
was 14.04 days (± 12.4) in women with BMI < 30 and 17.4 days (± 21.4) in those with
BMI > 30. This difference was not statistically significant. Among the 19 patients
with a history of threatened abortion, the mean latency was 13.6 days (± 12), compared
with 16.2 days (± 13.6) in the 86 patients without such history; again, the difference
was not statistically significant. In the comparison of patients who received tocolysis
(n = 27) and those who did not (n = 79), the mean latency was significantly longer in the tocolysis group (18.4 ± 19.1
days) than in the nontocolysis group (7.8 ± 8.5 days) (p < 0.05). Patients were categorized based on their CRP levels at admission: negative
(< 5 mg/L) and positive (> 5 mg/L). The negative CRP group exhibited a significantly
longer latent period of 18.9 days (± 17.05) compared with 8.47 days (± 17.07) in the
positive CRP group. When classified by AFI at admission (< 50 vs. > 50 mm), the latent
period was 14.8 days (± 17.5) in the < 50 mm group and 17.6 days (± 18.7) in the > 50 mm
group; however, this difference was not statistically significant. Patients with UTIs
had a mean latency of 15.15 days (± 15), while those without infection had a latency
of 16.1 days (± 19.1), with no significant difference observed ([Table 2]).
Table 2
Relationship between study group characteristics and latent period duration
|
N = number of patients
|
Latent period duration (d)
Mean (SD)
|
p
|
|
Body mass index < 30
Body mass index > 30 (kg/m2)
|
52
54
|
14.04 (12.4)
17.4 (21.4)
|
0.9
|
|
Threatened abortion Yes
Threatened abortion No
|
20
86
|
13.6 (12)
16.2 (13.6)
|
0.6
|
|
Tocolysis Yes
Tocolysis No
|
27
79
|
18.4 (19.1)
7.8 (8.5)
|
< 0.05
|
|
Vaginal birth
Cesarean
|
32
74
|
11.53 (16.08)
17.58 (18.08)
|
0.06
|
|
CRP < 5 (mg/L)
CRP > 5(mg/L)
|
54
32
|
18.9 (17.05)
8.47 (17.07)
|
< 0.05
|
|
AFI < 50 (mm)
AFI > 50 (mm)
|
70
36
|
14.8 (17.5)
17.6 (18.7)
|
0.5
|
|
Urinary tract infection Yes
Urinary tract infection No
|
39
67
|
15.15 (15.008)
16.10 (19.1)
|
0.7
|
|
Vertex presentation
Nonvertex presentation
|
68
38
|
14.5 (15)
17.9 (21.6)
|
0.7
|
|
Nulliparous
Multiparous
|
30
76
|
17.6 (21.1)
15.01 (16.1)
|
0.9
|
|
Singleton pregnancy
Twin pregnancy
|
95
11
|
15.3 (16.4)
18.9 (26.7)
|
0.5
|
Abbreviations: AFI, amniotic fluid index; CRP, C-reactive protein; SD, standard deviation.
Note: The boldfaced values indicate statistical significance (p < 0.05).
The relationship between latent period duration and tocolysis use in patients with
and without chorioamnionitis was analyzed. The mean latency was 13.8 days (SD = 8.5)
in patients diagnosed with chorioamnionitis and 16.11 days (SD = 18.9) in those without.
This difference was not statistically significant (p > 0.05). Regarding tocolysis administration, 17.6% (n = 3) of patients with chorioamnionitis received tocolysis, whereas 82.3% (n = 14) did not. Among those without chorioamnionitis, 26.9% (n = 24) received tocolysis and 73% (n = 65) did not. The difference in tocolysis use between the two groups was also not
statistically significant (p > 0.05). These findings suggest that chorioamnionitis does not significantly influence
latency duration or the likelihood of tocolysis administration ([Table 3]).
Table 3
Relationship between latent period duration and tocolysis use in chorioamnionitis
|
Chorioamnionitis Yes (n = 17)
|
Chorioamnionitis No
(N = 89)
|
p
|
|
Mean latent period duration,
d (SD)
|
13.8 (8.5)
|
16.11 (18.9)
|
0.2
|
|
Tocolysis Yes
Tocolysis No
|
3 (%17.6)
14 (%82.3)
|
24 (%26.9)
65 (%73)
|
0.5
|
Abbreviation: SD, standard deviation.
Patients were also divided into two groups based on the gestational age at the time
of membrane rupture: < 24 and ≥ 24 weeks. Demographic and clinical parameters, including
age, gravidity, parity, number of abortions, latency duration, birth weight, APGAR
score, BMI, and AFI at admission, were compared between the groups. Birth weight and
APGAR scores were significantly higher in the ≥ 24 weeks group. Although the latency
period was longer in the < 24 weeks group (17.2 ± 21.8 days), this difference was
not statistically significant ([Table 4]).
Table 4
Comparison of patients' characteristics according to PROM week
|
< 24 week (n = 48) (mean ± SD)
|
24–28 week (n = 58)
(mean ± SD)
|
p
|
|
Age (y)
|
30.7 (7.2)
|
28.6 (7.04)
|
0.137
|
|
Gravida
|
2.98 (1.8)
|
2.7 (1.7)
|
0.472
|
|
Parity
|
1.56 (1.6)
|
1.16 (1.1)
|
0.127
|
|
Abortion
|
0.44 (0.9)
|
0.6 (1.2)
|
0.395
|
|
Latent period duration (d)
|
17.2 (21.8)
|
14.55 (13.2)
|
0.443
|
|
Birth weight (g)
|
760 (390)
|
1168 (339)
|
< 0.05
|
|
APGAR
|
3.1 (2)
|
5.1 (1.6)
|
< 0.05
|
|
Body mass index
(kg/m2)
|
29.4 (3.2)
|
30.1 (2.6)
|
0.2
|
|
AFI (mm) measured at first hospital admission
|
43.6 (45)
|
44.5 (42.6)
|
0.9
|
Abbreviations: AFI, amniotic fluid index; APGAR, Appearance, Pulse, Grimace, Activity,
and Respiration; PROM, premature rupture of membranes; SD, standard deviation.
Note: The boldfaced values indicate statistical significance (p < 0.05).
Patients were further categorized based on the latency duration (< 7 and ≥ 7 days).
Age, gravidity, number of miscarriages, gestational age at PROM, AFI, CRP, mode of
delivery, presence of multiple gestation, and neonatal complications were compared.
The CRP level at admission and mode of delivery were found to be statistically significant.
The mean CRP level at admission was 27.45 mg/L in the < 7 days group and 13.06 mg/L
in the ≥ 7 days group, with the difference being statistically significant. Regarding
delivery mode, the < 7 days group included 19 vaginal deliveries and 25 C/S, while
the ≥ 7 days group included 13 vaginal deliveries and 49 C/S, again with a statistically
significant difference ([Table 5]).
Table 5
Relationship between latent period, maternal, and perinatal outcomes
|
Latent period < 7 days
N = 44
|
Latent period > 7 days
N = 62
|
p
|
|
Age
(y)
|
29.7
|
29.5
|
0.7
|
|
Gravida
|
2.95
|
2.76
|
0.5
|
|
Number of abortions
|
0.52
|
0.55
|
0.6
|
|
PROM
(wk)
|
24.4
|
24.1
|
0.9
|
|
AFI measured at first hospital admission (mm)
|
40.47
|
46.62
|
0.4
|
|
CRP measured at first hospitalization (mg/L)
|
27.45
|
13.06
|
< 0.05
|
|
Body mass index
(kg/m2)
|
29.6
|
29.9
|
0.6
|
|
Birth type
|
|
|
< 0.05
|
|
Vaginal birth
Cesarean
|
19 (%43.1)
25 (%56.8)
|
13 (%20.9)
49 (%79)
|
|
Vertex presentation
Nonvertex presentation
|
29 (%65.9)
15 (%34)
|
39 (%62.9)
23 (%37)
|
0.7
|
|
Singleton pregnancy
Multiple pregnancy
|
38 (%86.3)
6 (%13.6)
|
57 (%91.9)
5 (%8.06)
|
0.2
|
Abbreviations: AFI, amniotic fluid index; CRP, C-reactive protein; PROM, premature
rupture of membranes.
Note: The boldfaced values indicate statistical significance (p < 0.05).
Of the 106 neonates with a history of periviable PPROM, 25 died during the neonatal
period. A total of 31 neonates were followed up in our clinic, allowing for evaluation
of postnatal outcomes. The remaining 50 neonates were referred to external health
care institutions, and their outcome data were not available for further analysis
([Fig. 1]).
Fig. 1 Flowchart of the patient selection process and neonatal outcomes. Among 1,462 cases
of premature rupture of membranes (PROM), 135 cases met the criteria for periviable
PPROM between 22 and 26 weeks of gestation. After excluding 29 cases due to missing
data or failure to meet the inclusion criteria, 106 cases were analyzed. Of these,
25 resulted in neonatal death, 31 neonates were admitted to the neonatal intensive
care unit (NICU) in our clinic, and 56 cases were referred to other institutions with
unavailable outcome data.
Neonates with a latency period shorter than 7 days had a higher incidence of retinopathy
of prematurity compared with those with a latency period ≥ 7 days (66.7% vs. 56%,
p = 0.5). Similarly, respiratory distress syndrome was more prevalent in the shorter
latency group (83.3% vs. 72%, p > 0.5). Intraventricular hemorrhage (IVH) demonstrated a notable difference, occurring
in 50% of neonates in the < 7 days group compared with 16% in the ≥ 7 days group (p = 0.1). The incidence of necrotizing enterocolitis (NEC) was comparable between groups
(16.6% vs. 12%, p > 0.5). Although the observed difference in IVH was clinically relevant, none of
the outcomes reached statistical significance ([Table 6]). Chorioamnionitis was identified in 8 out of 31 neonates. According to Fisher's
exact test, there was a statistically significant association between chorioamnionitis
and NEC (p < 0.05).
Table 6
Relationship between neonatal outcomes and latent period duration
|
Latent period < 7 days
N = 6
|
Latent period > 7 days
N = 25
|
p
|
|
ROP (n/total) (%)
|
4/6 (%66.7)
|
14/25 (%56)
|
0.5
|
|
RDS (n/total) (%)
|
5/6 (%83.3)
|
18/25 (%72)
|
0.5
|
|
İVH (n/total) (%)
|
3/6 (%50)
|
4/25 (%16)
|
0.1
|
|
NEC (n/total) (%)
|
1/6 (%16.6)
|
3/25 (%12)
|
0.5
|
Abbreviations: IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; RDS,
respiratory distress syndrome; ROP, retinopathy of prematurity.
Multivariable logistic regression analysis identified factors independently associated
with latent period duration (> 7 vs. < 7 days). Tocolysis administration was significantly
associated with a prolonged latent period, with an odds ratio (OR) of 2.894 (95% confidence
interval [CI]: 1.059–7.909, p < 0.05). Elevated CRP levels (> 5 mg/L) were inversely related to prolonged latency,
with an OR of 0.195 (95% CI: 0.072–0.531, p < 0.05), indicating that higher CRP levels reduced the odds of a latent period longer
than 7 days. Urinary tract infection was significantly associated with a shorter latent
period, with affected individuals having an 84% lower odds of experiencing latency
longer than seven days (OR: 0.159; 95% CI: 0.03-0.85; p < 0.05). This association was statistically significant ([Table 7]).
Table 7
Multivariable logistic regression analysis of factors associated with latent period
duration (< 7 vs. > 7 days)
|
Odds ratio
|
Confidence interval (95%)
|
p
|
|
Tocolysis
|
2.894
|
1.059–7.909
|
< 0.05
|
|
Fetal position
|
1.098
|
0.429–2.812
|
0.845
|
|
Oligohydramnios
|
1.804
|
0.719–4.529
|
0.209
|
|
CRP > 5 (mg/L)
|
.195
|
0.072–0.531
|
< 0.05
|
|
BMI > 30 (kg/m2)
|
1.311
|
0.533–3.224
|
0.556
|
|
Urinary tract infections
|
0.159
|
0.03–0.85
|
< 0.05
|
|
PROM weeks, > 24 week
|
1.579
|
0.637 - 3.911
|
0.324
|
Abbreviations: BMI, body mass index; CRP, C-reactive protein; PROM, premature rupture
of membranes.
Discussion
PROM refers to chorioamniotic membrane rupture with amniotic fluid leakage before
the onset of labor. When it occurs before 37 weeks of gestation, it is termed PPROM.
Periviable PROM, defined as membrane rupture between 200/7 and 256/7 weeks, does not have a universally standardized definition. This study analyzed maternal,
fetal, and laboratory parameters to identify predictors of latency period duration,
contributing to the literature by guiding PPROM management and improving neonatal
outcomes. The objective of this study was to assess the factors influencing the latent
period duration in cases of periviable PPROM and to investigate the effects of maternal
and fetal characteristics on this period. The latent period, defined as the interval
between the diagnosis of membrane rupture and the onset of labor or delivery, is a
key determinant of neonatal outcomes.[7]
A 2011 Cochrane review evaluated the efficacy of tocolytic therapy in PPROM, analyzing
408 women. Seven studies compared women who received tocolytics with those who did
not. The analysis showed that tocolytic therapy was associated with a prolonged latency
period but increased the risk of chorioamnionitis, with no significant differences
in neonatal outcomes.[8] There is no consensus on the use of tocolysis in PPROM.[9] In our study, tocolysis was associated with a statistically significant prolongation
of the latent period. However, no significant differences were observed in the incidence
of chorioamnionitis or adverse neonatal outcomes. These findings may be attributed
to close clinical surveillance, standardized management protocols, and the limited
sample size, which may have reduced the statistical power to detect subtle differences.
Further studies involving larger cohorts and heterogeneous populations are warranted
to confirm these associations and enhance the generalizability of the results.
In a retrospective study conducted over a 10 year period, 1,399 patients with PPROM
were examined to evaluate factors associated with the latent period. It was found
that nulliparity, lower gestational age, presence of chorioamnionitis, and oligohydramnios
were significantly associated with a shortened latency period.[10] In contrast to these findings, the present study did not demonstrate a significant
association between nulliparity, lower gestational age, or oligohydramnios and the
duration of the latent period. However, although the difference was not statistically
significant, cases with oligohydramnios showed a tendency toward a shorter latent
period compared with those with normal amniotic fluid levels.
In the literature, prophylactic antibiotic use has been associated with a prolonged
latent period and improved neonatal outcomes in cases of PPROM. Studies suggest that
antibiotics may assist in prolonging gestation by reducing the risk of intra-amniotic
infection and inflammation, thereby enhancing neonatal outcomes.[11]
[12] In this study, antibiotic prophylaxis was administered to nearly all patients, and
the lack of a control group prevented meaningful comparisons between antibiotic use
and the latent period. These findings suggest that while prophylactic antibiotic use
may be associated with a prolonged latent period, the absence of a control group limits
the ability to make definitive inferences, highlighting the need for prospective studies
with appropriate control groups to better evaluate this relationship.
Several studies have explored CRP levels in pregnant women and their potential to
predict preterm birth, PROM, and chorioamnionitis. While CRP is a limited marker for
detecting histological chorioamnionitis and microbial invasion, extremely high levels
(> 95th percentile) may have some predictive utility. However, its low diagnostic
sensitivity limits its clinical reliability.[13]
[14]
[15] The literature highlights the predictive value of interleukin-6 and CRP levels for
intra-amniotic infection, demonstrating that both markers can serve as reliable indicators
for diagnosing this condition.[16] In this study, patients with CRP > 5 mg/L had a significantly shorter latent period
(18.9 vs. 8.4 days), suggesting that systemic inflammation may contribute to the initiation
of labor. Given CRP's low sensitivity, it should be interpreted in conjunction with
other clinical and laboratory parameters.
Studies in the literature indicate that patients with chorioamnionitis tend to have
a lower gestational age at diagnosis and a prolonged latency period.[17] In our study, although patients with chorioamnionitis experienced earlier membrane
rupture and delivery, the difference in the latent period was not statistically significant.
These findings suggest that chorioamnionitis may trigger early membrane rupture and
preterm birth, but its effect on latency duration remains unclear. Factors such as
inflammatory severity, individual variations in immune response, and the use of antibiotics
and tocolytics may influence outcomes. Additionally, microbial invasion and host response
appear to play a role in shaping the latent period. Further research is needed to
better understand these relationships.
A meta analysis of 33 studies reported a significant association between histopathologically
diagnosed chorioamnionitis and the development of NEC.[10] The development of NEC is recognized as one of the significant neonatal complications
associated with chorioamnionitis. Research indicates that the inflammatory processes
and immune responses triggered by chorioamnionitis may contribute to the development
of NEC, particularly in premature neonates.[18] In this study, NEC was observed in 4 out of 31 newborns, with three cases occurring
in the chorioamnionitis group. A significant association was found between chorioamnionitis
and NEC (p = 0.043). These findings indicate a significant association between chorioamnionitis
and the development of NEC. Intrauterine inflammation may compromise the integrity
of the fetal intestinal barrier, thereby increasing the risk of NEC. Additionally,
the elevated incidence of prematurity associated with chorioamnionitis could be an
important contributing factor to NEC development.
The literature reports varying C/S rates in patients with PPROM. Several studies have
demonstrated that the C/S rate increases with lower gestational age and extended latency
periods.[19] Manuck and Varner reported that the C/S rate increases in pregnancies prior to the
25th week of gestation.[20] In this study, the latent period was divided into two groups: less than 7 days (44
patients) and more than 7 days (62 patients). The C/S rate was significantly higher
in the > 7 days group (79% vs. 56%, p = 0.01). Although C/S rates were higher in patients with membrane rupture after 24
weeks (60% vs. 77%), this difference was not statistically significant (p = 0.055). These findings suggest that a prolonged latent period may increase C/S
rates, possibly due to a greater tendency toward surgical delivery to mitigate potential
complications. Additionally, the lack of significance in the > 24 weeks group indicates
that other clinical factors beyond gestational age may influence delivery decisions.
The main limitation of this study is its retrospective design, which carries the risk
of selection bias and limits the ability to establish causal relationships. Data were
obtained from archived medical records and the hospital registration system, which
may increase the risk of data incompleteness or inaccuracy. This may affect the reliability
and accuracy of the findings, particularly for clinical outcomes. Additionally, the
high neonatal referral rate at our center may have introduced referral bias, potentially
influencing neonatal outcome data. The single center design also limits the generalizability
of the results to wider populations due to variations in clinical practices and patient
demographics across different settings.
The multivariable logistic regression analysis identified several factors associated
with latent period duration in patients with periviable preterm premature rupture
of membranes (PPROM). Tocolysis significantly increased the likelihood of a latent
period longer than seven days (OR: 2.894, 95% CI: 1.059 -7.909, p < 0.05), indicating its effectiveness in prolonging pregnancy. Elevated CRP levels
(>5 mg/L) were strongly associated with a shorter latent period (OR: 0.195, 95% CI:
0.072-0.531, p < 0.05), highlighting the role of systemic inflammation in the timing of delivery.
Urinary tract infection was significantly associated with a shorter latent period,
with affected individuals having an 84% lower odds of experiencing latency longer
than seven days. Factors such as fetal position, oligohydramnios, BMI > 30, and membrane
rupture after 24 weeks were not significantly associated with latent period duration
(p > 0.05). These findings emphasize the importance of managing inflammation and infections
to optimize pregnancy outcomes, while tocolysis remains a key intervention for prolonging
latency in eligible cases.
The most valuable aspect of this study is the inclusion of periviable PROM patients,
which allows for a detailed examination of this specific patient population. While
various approaches to managing this group exist in the literature, this study provides
notable contributions to the understanding of periviable PROM cases. The study addresses
key considerations in counseling pregnant women, including options for expectant management
or pregnancy termination, and offers a comprehensive evaluation of factors influencing
the latent period, delivery methods, and maternal and neonatal outcomes. In this regard,
the study serves as a valuable guide for clinical decision making, offering important
information for health care professionals involved in the management of periviable
PROM. Furthermore, with its robust sample size and in-depth analysis, the study sheds
light on clinical practices and makes important contributions to both maternal and
neonatal health.
Conclusion
Periviable PPROMs is associated with various maternal and neonatal complications,
posing significant challenges in clinical management. The duration of the latent period
directly impacts outcomes, increasing the risk of conditions such as chorioamnionitis,
preterm birth, and neonatal morbidities, including NEC. A key strength of this study
lies in its exclusive focus on patients within the periviable period, enabling a detailed
examination of this high risk population. Early identification and accurate assessment
of risk factors, with a particular focus on inflammation and prolonged latency, are
essential for optimizing clinical outcomes. Therefore, defining these risk factors
and implementing evidence-based interventions are critical to improving both maternal
and neonatal prognoses in cases of periviable PPROM.
