Determination of Factors Affecting the Latent Period of Periviable Premature Rupture of Membranes: Cases and Evaluation of Newborn Outcomes

Abstract

Background

This study aimed to determine factors influencing the latent period in pregnant women with periviable preterm premature rupture of membranes (PPROM) between 22 and 26 weeks of gestation.

Methods

A retrospective analysis of 106 pregnant women who delivered at our hospital between 2017 and 2021 was conducted. Diagnosis was confirmed using sterile speculum examination or the AmniSure test. Standard treatment included antibiotics, steroids, and tocolytic therapy. Maternal and fetal data, including C-reactive protein (CRP) levels, hemogram parameters, birth weight, and APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) scores, were collected from medical records.

Results

A statistically significant difference was observed between CRP levels and the latent period. Patients with negative CRP values (< 5 mg/L) had a longer latent period (18.9 ± 17.05 days) compared with those with positive CRP values (> 5 mg/L, 8.47 ± 17.07 days). Chorioamnionitis was detected in 8 of 31 newborns, with a significant association between chorioamnionitis and necrotizing enterocolitis (NEC) (p = 0.043).

Conclusıon

PPROM poses significant maternal and neonatal risks, with the latent period directly impacting outcomes. Elevated CRP levels at admission were linked to shorter latency (p < 0.05), while tocolytic therapy prolonged latency without improving neonatal outcomes. The association between chorioamnionitis and NEC (p = 0.043) highlights the importance of early identification and management of risk factors. Individualized treatment with tocolytics, antibiotics, and corticosteroids is essential to optimize maternal and neonatal outcomes.

 

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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.

 

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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.

 

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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.

 

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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.

 

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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.

 

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Conflict of Interest

None declared.

Acknowledgment

Thanks to all the peer reviewers for their opinions and suggestions.

Availability of Data and Materials

All data and materials are available on reasonable request from the corresponding author.

Authors' Contributions

All authors read and approved the final manuscript. All authors contributed to editorial changes in the manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Ethics Approval and Consent to Participate

All subjects gave their informed consent for inclusion before they participated in the study. The study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Ethics Committee of İzmir Tepecik Training and Research Hospital with the decision number 2021/10–29.

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Publication History

Article published online:
10 July 2025