Periviable preterm prelabor rupture of membranes: Outcomes of pregnancies following expectant management

doi:10.21203/rs.3.rs-4120696/v1

Background: Periviable preterm rupture of membranes (PPROM) is associated with increased risk of perinatal morbidity and mortality. We aimed to assess the outcomes and predictive factors of ekspectant management in pregnancies with periviable preterm prelabor rupture of membranes (PPROM).

Methods: This was a retrospective study from January 2015 through December 2019. Women diagnosed with PPROM in the periviable period (20+0 to 25+6 weeks’ gestation) were included. Maternal demographics, clinical characteristics, and neonatal outcomes were reviewed. Clinical data were obtained from the medical records of a single center. Predictive factors for assessed using receiver-operator characteristic (ROC) curves.

Results: A total of 142 women with mid-trimester PPROM were evaluated. Among this, 119 (83.8 %) were managed expectantly and included in this study. Forty-five (37.8%) of these pregnancies benefited from expectant management; that is, the newborns survived to discharge from NICU. The remaining 74 pregnancies (62.2%) resulted in pre-viable births, stillbirths, deaths in the delivery room, and neonatal deaths. Pregnancies benefiting from expectant management had a longer latency period, had a greater birth weight, and were born at a more advanced GA compared to women who did not benefit from expectant management. Diagnostic cut-off values were obtained by Receiver-operator characteristic (ROC) curves for this indicators and their combination. ROC curve analysis identified GA at delivery ≤23 weeks, latency period ≤9 days, and birth weight ≤640 grams as predictors of unsuccessful expectant management.

Conclusions: Periviable PPROM is associated with poor neonatal outcomes with an overall survival rate of 37.8%. If the mother and fetus stabil during the expectant period, neonatal outcomes can be improved by increasing GA at birth, birth weight and latency period.

Preterm premature rupture of membranes

periviable

chorioamnionitis

preterm delivery

The period between 20 + 0 and 25 + 6 weeks gestation, when there is a high probability of neonatal death or significant neonatal morbidity, is the earliest stage of fetal maturity and is called the periviable period (1). Although the prevalence of preterm prelabor rupture of membranes (PPROM) is less common before 26 or 27 weeks of gestation (0.5%) deliveries occurring during this period are associated with worse neonatal outcomes (2). Respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infection, and neurodevelopmental impairment are some of the morbidities experienced by infants surviving extreme prematurity. Neonatal mortality and most neonatal morbidities decrease with increasing gestational age (GA) at delivery (3). If the condition of the fetus and mother are stable and there is no indication for urgent delivery, such as perinatal infection, abruptio placentae, or umbilical cord compression, it has been observed that neonatal outcomes are not worse if the latency period, the interval between membrane rupture and delivery, is prolonged (4, 5).

The major complicating factor of periviable PPROM is the appropriateness of expectant management or an option for pregnancy termination (especially before 22 gestational weeks) by parents due to probably poor neonatal outcomes, which causes both socioeconomically and psychologically devastating effects for parents. As a result of the advancement in neonatal intensive care, including the use of antibiotics, antenatal steroids and neuroprotective magnesium sulfate, postnatal surfactant, and optimizing respiratory support, outcomes for infants given birth following PPROM or threshold of viability were better than previously expected (1).

In this study, we aimed to determine the characteristics affecting perinatal and neonatal morbidity and mortality in periviable PPROM cases by evaluating the perinatal, neonatal, and maternal outcomes of periviable PPROM cases.

This retrospective cohort study was performed between January 2015 and December 2019 in the Maternal-Fetal Medicine Unit of Health Science University, Izmir Tepecik Research and Training Hospital. The data were obtained from the hospital's digital recording system. This study was conducted following the Helsinki Declaration Ethical Standards and was approved by the local ethics committee with the approval number 2019/15 − 8.

Patients

Women diagnosed with PPROM during the periviable period (from 20 + 0 to 25 + 6 weeks’ gestation) were evaluated and patients with expectant management were included in the study. Pregnancies known to have fetal structural or chromosomal abnormalities, multiple pregnancies, the presence of labor at the time of diagnosis or giving birth within 24 hours of diagnosis were excluded.

Initial approach

The diagnosis of PPROM was based on a maternal history of leaking fluid and a sterile speculum examination. When the pooling of amniotic fluid in the posterior fornix was noted, no additional tests were used. If the amniotic fluid was not seen, an assay for placental alpha microglobulin-1 protein in the vaginal fluid was used to confirm the diagnosis (6). Following the diagnosis of PPROM, all pregnancies were evaluated for the presence of labor, infection and fetal well -being, fetal presentation, and amniotic fluid status on ultrasound examination. Oligohydramnios was defined as an amniotic fluid index (AFI) < 5 cm and/or a deep vertical pocket (DVP) < 2 cm. Anhydramnios was defined as AFI < 3 cm. GA was determined by the date of the last menstrual period and confirmed by a crown-rump length (CRL) at a first-trimester ultrasound.

Pregnancy management

We discussed the potential risks and benefits of expectant management versus termination of pregnancy with parents for all pregnancies before 22 weeks gestation, and offered the option of pregnancy termination by induction of labor. Patients who preferred expectant management before 22 weeks and all pregnancies over 22 weeks were hospitalized and monitored for maternal and fetal well-being. Patients who refused hospitalization were discharged and scheduled for twice-weekly outpatient visits. We recommended delivery at 34 weeks gestation unless the following occurred: nonreassuring fetal heart rate, placental abruption, clinical chorioamnionitis, cord prolapse, or the presence of spontaneous labor. Inpatients were closely monitored for signs and symptoms of chorioamnionitis and fetal well- being. We performed daily non-stress tests, twice-weekly biophysical profiles and AFI status, daily maternal temperature, presence of uterine tenderness, presence of foul-smelling amniotic fluid, maternal heart rate, and twice-weekly assessment of white blood cell (WBC) count, and C-reactive protein (CRP) levels. All women were treated with prophylactic antibiotics, preferably azithromycin, 1 gram orally, plus ampicillin, 2 grams intravenously 4 times a day for 2 days, and then amoxicillin 500 mg orally 3 times daily for an additional 5 days. This resulted in a 7–10 day course of prophylactic antibiotics. Women who presented between 23 and 34 weeks gestation were given two doses of betamethasone 24 hours apart. Prophylactic tocolysis was only used in selected patients to delay delivery by 48 hours to administer corticosteroids (7). Only 14 patients received tocolysis, and we did not include these patients in the study. Magnesium sulfate was used for fetal neuroprotection in women with the possibility of an immediate delivery between 24 and 32 weeks gestation, and active resuscitation was performed for all infants born after 22 weeks.

Outcomes

Maternal demographic characteristics and pregnancy and neonatal outcomes were evaluated. Risk factors for PPROM, such as antepartum hemorrhage, PPROM and history of multiple D&C, smoking, cervical cerclage, and short cervix (cervix length < 25 mm by transvaginal ultrasound), were examined. Maternal demographics included age, gravidity, parity, body mass index, and refugee. Maternal complications included chorioamnionitis, retained placenta, postpartum hemorrhage, sepsis, and death. Pregnancy outcomes included sonographic and laboratory findings, latency period (the days between membrane rupture and delivery), indication for delivery, GA at delivery, and delivery mode. Neonatal outcomes included gender, birth weight, admission to the neonatal intensive care unit (NICU), death, and major morbidities. Major neonatal morbidities included severe BPD, NEC ≥ stage 2, grades III or IV IVH, ROP ≥ stage 3, and PVL.

We compared pregnancies that benefited from expectant management, those with neonatal survivors, to those which did not benefit, previable births, deaths in the delivery rooms, stillbirths, and neonatal deaths.

Statistical analysis

The data were evaluated using SPSS Statistics 24.0 (IBM Corp., Armonk, New York, USA) and IBM AMOS statistical package programs. Descriptive statistics, including unit number (n), percentage (%), mean ± standard deviation, smallest value (min), largest value (max), median, and interquartile range (IQR) were evaluated. Data with a normal distribution of quantitative variables was evaluated by the Shapiro- Wilk normality test and Q-Q graphs. The homogeneity of group variances was evaluated with the Levene Test. Comparisons between two groups with normally distributed data used the independent sample t- test and Mann-Whitney U test. The relationship between categorical variables was evaluated in 2 x 2 and r x c tables by Fisher’s exact test, continuity correction test, and Pearson’s Chi-Square test. A p- value < 0.05 was considered statistically significant. Comparisons of groups with more than two subcategories were evaluated using one-way variance analysis (ANOVA) or the Kruskal-Wallis analysis depending on normality. Receiver-operator characteristic (ROC) curves were drawn for determining factors related to not-benefiting expectant management.

Between January 2015 and December 2019, 142 pregnancies were diagnosed with periviable PPROM in our clinic. A total of 14 (9.8%) pregnancies were excluded based on multifetal pregnancies, 3 (2.1%) were excluded due to lethal fetal anomalies, 4 (2.8%) were lost to follow-up, and 2 (1.4%) opted for termination before 22 weeks gestation. The remaining 119 (83.8%) women were managed expectantly and included in this study. The mean maternal age was 29.4 ± 6.6 years, and 17.6% were primigravid. The median GA at admission was 23 (IQR 2) weeks. Study flow chart and outcomes of pregnancies are shown in Fig. 1.

Benefit from expectant management

Forty-five of these pregnancies benefited from expectant management; that is, the newborns survived to discharge from NICU. The remaining 74 pregnancies resulted in pre-viable births, stillbirths, deaths in the delivery room, and neonatal deaths. A comparison of the characteristics and outcomes of those who benefited from expectation management and those who did not are presented in Table 1. The maternal demographics and risk factors were similar between the two groups. Four women from the not-benefited group had PPROM after an invasive diagnostic procedure (within 15 days after genetic amniocentesis), and four women had pregnancies with assisted reproductive techniques (ART). The rate of pregnancies with outpatient follow- up was higher in the benefited group (26.7% versus 8.1%, p < 0.05).

The median latency period was 7 Interquartile Range (IQR 21) days, with a range of 1–80 days, and nearly half of the fetuses (47.1%) were born during the first seven days of latency. Pregnancies benefiting from expectant management had a longer latency period, [16 (IQR 35) versus 4.5 (IQR 14.2) days, p < 0.05] compared with the not-benefiting group. The median AFI was similar between the two groups [30, IQR (22.5) versus 25, IQR (60), p = 0.644]. Oligohydramnios was present at admission in 46.7% of those who benefited from expectant management, but it was present in only 27% of those who did not p = 0.060. Among laboratory findings, only CRP levels at admission were lower in the group benefiting from expectancy management (8.5 (IQR 9.0) vs. 16.0 (IQR 27.0) mg/L; p < 0.001).

The infants of pregnancies benefiting from expectant management were born at a more advanced GA, [26 (IQR 4.5) versus 23 (IQR 2.2) weeks, p < 0.05]; and had a higher birth weight, [910 (IQR 570) versus 590 (IQR 226) grams, p < 0.05]. The most majority of fetuses (82.3%) were born extremely preterm, < 28 weeks. Only two infants (1.7%) were delivered at 34 weeks gestation. The mode of delivery was different among groups and the rate of cesarean section was significantly higher in the benefiting group (75.6% versus 50%, p = 0.010). Indications of delivery were similar between the two groups (p = 0.153) and the most common indication of delivery before 34 gestational weeks was the spontaneous onset of labor (57.1%)

Maternal complications were similar between the two groups, and no maternal sepsis or death occurred during the expectant management period. The main causes of maternal morbidity were clinical chorioamnionitis (12/119, 10.0%), retained placenta (8/119, 6.7%), postpartum hemorrhage (2/119, 1.7%), and in one case (0.8%) hysterectomy because of placenta accreata spectrum.

Outcomes of neonates

Of 119 expectantly managed pregnancies, 101 (84.8%) newborns were alive and admitted to the NICU; 45 (44.5% of live births or 37.8% of the overall cohort) of these survived to discharge, and among this, 15 (33.3% of survivors or 12.6% of the overall cohort) had no major morbidities at NICU discharge. However, 30 (66.7% of survivors or 25.2% of the overall cohort) had at least one major morbidity at discharge. Table 2 shows the neonatal demographics and outcomes of neonatal survivors. The median gestational age of delivery was 26 (IQR, 4.5) weeks, and the median birth weight was 910 (IQR, 570) gr in neonatal survivors. The most common neonatal complications were associated with respiratory problems, RDS (84.4%), and severe BPD (60.0%). The other major morbidities included PDA (57.8), ROP stage 3–4 (24.4%), PVL (11.1%), NEC ≥ stage 2–3 (11.1%), and IVH > grade 2 (4.4%).

A total of 56 (55.4%) infants died in the postpartum period, primarily (58.9%) in the first seven days following birth (early neonatal death). The primary cause of early neonatal deaths was pulmonary hypoplasia (79%).

Receiver operator characteristic (ROC) curve analysis was conducted to estimate the sensitivity and specificity of predicting the presence of non-beneficial expectancy management based on four indicators, including GA at admission, GA at delivery, latency period, and birth weight (Fig. 2). GA at admission (weeks) can not predict of not-benefiting expectant management (p = 0.079). GA at delivery, latency period, and birth weight were valuable predictors of adverse outcomes. Specifically, GA at delivery ≤ 23 weeks, latency period ≤ 9 days, and birth weight ≤ 640 grams were associated with an increased risk of not benefiting from expectant management. Table 3 showed the cut-off points and sensitivity analysis for GA at delivery, latency period, birth weight and their combination for not-benefiting ekspectant management.

Combined ROC analysis was performed with GA at delivery, latency period and birth weight. The area under the curve was 0.78 (sensitivity 90.38%, specificity 50.00%, p < 0.001), showing that combination probability > 0.4414 was significantly related to an increased risk of the presence of not-benefiting expectant management in the combined ROC (Fig. 3).

In this study, we examined the association between maternal and perinatal characteristics of periviable PPROM cases with perinatal and neonatal outcomes. The controversial problem with periviable PPROM is, on the one hand, the increased rates of neonatal morbidity and mortality due to extremely preterm deliveries, and on the other hand, the high risk of maternal infections and other maternal complications during the expectant management period. Therefore providing proper counseling to families about the benefits and risks of management options is important. Our results revealed that approximately one-third of pregnancies benefited from expectant management, with newborns surviving to discharge from the NICU, and one-third of these infants had no major morbidities during discharge. Notably, the latency period, GA at delivery, and birth weight emerged as crucial factors influencing the success of expectant management. Pregnancies with longer latency periods, higher GA at delivery, and higher birth weight were more likely to benefit from expectant management, highlighting the importance of these parameters in clinical decision-making.

In recent years, there have been many studies published about neonatal survival in PPROM cases. In prior studies with a similar population, the overall neonatal survival rate ranged from 45.9–63.2%, and the discharge rate without major morbidity ranged from 17.9–76.7% (8–11). This suggests that our overall survival to discharge rate (37.8%) was relatively lower than previous studies despite our high live birth and NICU admission rate (84.8 %). We povided active resuscitation to infants born after 22 weeks, and noticed even if the infants respond to resuscitation, neonatal mortality rates are very high similar to the study by Anderson et al. (12). This difference in neonatal mortality may be related to postnatal care in the NICU, and the high incidence of neonatal mortality underscores the need for multidisciplinary neonatal care and emphasizes the challenges in managing extremely preterm infants deliver after PPROM. Another factor may be associated with persistent exposure to oligo-anhydramnios in the second trimester, which can be related to pulmonary hypoplasia and early neonatal deaths although the pregnancy resulted in a live birth. Lee et al.(13) described the significant relationship between persistent oligohydramnios and low survival rates in their study published in 2015. A statistically significant difference was not found between the two groups according to the presence of oligo-anhydramnios, but we evaluated the admission AFI levels and the presence of anhydramnios at any time, not persistent oligo-anhydramnios, and unknown length of oligo-anhydramnios exposure. These results are related to the variability of AFI during the latency period.

Considering the antenatal characteristics of the group benefiting from expectant management, higher outpatient rate, lower CRP levels at admission and higher cesarean section rate were not surprising findings. The relationship between maternal CRP levels and neonatal survival has been reported recently (14, 15). Since CRP is an inflammatory marker, it may indicate a relationship between chorioamnionitis and a short latency period and poor neonatal outcomes as a consequence of the short latency period. Similar to previous studies showing that outpatient follow-up can be safe in selected patients the benefit of expectant management was higher among women who were managed as outpatients (16–19). Our more active approach to hospitalized women included multiple digital vaginal examinations. This may have accelerated the onset of spontaneous labor and a shortening of latency because stimulation of the cervix can cause prostaglandin release, resulting in the onset of uterine contractions earlier GA at delivery, and poorer neonatal outcomes (20, 21). Nosocomial infection may be less common in patients who are followed as outpatients resulting in a longer latency period.

Consistent with the literature, within postpartum characteristics, we found that GA at birth, latency period, and birth weight were all higher in infants who survived than those who did not. Through ROC analysis, we established cut-off values for these three indicators and their combinations, thus identifying which pregnant women would not benefit from expectant management. Unlike previous studies, the difference between the two groups according to GA at PPROM could not be determined(22–24).

The main limitations of our study are its retrospective nature and relatively small sample size including single center data. Additionally, our study included only short-term neonatal outcomes. Our study also had its strengths. In this study, we included all features related to PPROM, as well as maternal and pregnancy characteristics, and examined all parameters that may affect the management of periviable PPROM cases.

In conclusion, expectant management can offer favorable outcomes in select cases of periviable PPROM, particularly in pregnancies with longer latency periods, higher GA at delivery, and greater birth weight. However, careful patient selection and close monitoring are essential to optimize outcomes and minimize complications. Further research is warranted to refine predictive models and improve risk stratification in this challenging obstetric population.

PPROM Preterm Prelabor Rupture of Membranes

RDS Respiratory distress syndrome

NEC Necrotizing Enterocolitis

IVH Intraventricular Hemorrhage

PVL Periventricular Leukomalacia

BPD Bronchopulmonary Dysplasia

ROP Retinopathy of Prematurity

GA: Gestational Age

AFI Amniotic Fluid Index

DVP Deep Vertical Pocket

WBC White Blood Cell

CRP C-Reactive Protein

NICU Neonatal Intensive Care Unit

ART Assisted Reproductive Techniques

IQR Interquartile Range

BMI Body Mass Index

Conflict of interest statement: The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was conducted following the Helsinki Declaration Ethical Standards and was approved by the Health Science University, Izmir Tepecik Research and Training Hospital local ethics committee with the approval number 2019/15-8.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Authors' contributions

MK designed the experiment. MK and OY analyzed and interpreted the data. MK and BKA wrote the manuscript. DA, MO and HG conceived the study and revised the manuscript. All authors read and approved the final manuscript.

Acknowledgements

Not applicable

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Table 1: Characteristics and Outcomes of Pregnancies

	Benefiting from expectant management	Not- benefiting from expectant management
	n= 45	n= 74	p value
Maternal age ^¶	29.6 + 7	29.1 + 6	0.735^*
Maternal age >35, n (%)	9 (20.0)	16 (21.6)	1.000**
Gravidity (IQR)	2 (2)	3 (1)	0.881***
Parity (IQR)	1 (2)	1 (2)	0.850***
Primipar, n (%)	29 (64.4)	56 (75.7)	0.269**
BMI (kg/m2) ^¶	26 + 4	27 + 4	0.682^*
Refugee, n (%)	6 (13.3)	10 (13.5)	1.000**
Risk factors of PPROM
Antepartum hemorrhage^µ , n (%)	10 (22.2)	16 (21.6)	1.000**
History of PPROM, n (%)	5 (11.1)	17 (23.0)	0.170**
History of multipl D&C, n (%)	8 (17.8)	10 (13.5)	0.715**
Smoker, n (%)	6 (13.3)	11(14.9)	1.000**
Cervical cerclage, n (%)	2 (4.4)	3 (4.1)	1.000
Cervical length, mm, n:45	29 (14)	32 (20)	0.668***
Short cervix, n= 45^ð n (%)	4 (22.2)	8 (29.6)	0.735*****
Type of follow up
Inpatient, n	33 (73.3)	68 (91.9)	0.013**
Outpatient, n	12 (26.7)	6 (8.1)	0.013**
GA at admission (weeks)^¶	22+ 1.6	22+ 1.3	0.144^*
Latency period (days)	16 (35)	4.5 (14.2)	0.000***
Latency<7 days, n (%)	13 (28.9)	43 (58.1)	0.004**
Sonographic findings
AFI (mm)	30 (22.5)	25 (60)	0.644***
Normal, n (%)	7 (15.6)	22 (29.7)	0.060****
Oligohydramnios, n (%)	21 (46.7)	20 (27.0)
Anhydramnios, n (%)	17 (37.8)	32 (43.2)
Anhydramnios at any time, n (%)	22 (48.9)	39 (52.7)	0.830**
Breech presentation, n (%)	22 (48.9)	34 (45.9)	0.902**
Laboratuary findings
WBC count at admission (x10³ /uL) ^¶	13573 + 3100	13900 + 4400	0.666^*
WBC> 15000 x10³ /uL, n (%)	15 (33.3)	27 (36.5)	0.880**
CRP levels at admission (mg/L), n:90	8.5 (11)	16 (27)	0.010***
CRP>5 mg/dL, n: 90 (%)	26 (72.2)	40 (83.3)	0.337**
GA at delivery (weeks)	26 (4.5)	23 (2.2)	0.000***
Birth weight (grams)	910 (570)	590 (226)	0.000***
Delivery before 28 gw, n (%)	30 (66.7)	66 (89.2)	0.017****
Type of delivery, n (%)
Vaginal delivery	11 (24.4)	37 (50.0)	0.010****
Cesarean section	34 (75.6)	37 (50.0)	0.010****
Fetal gender, n (%)
Female	29 (64.4)	34 (45.9)	0.077**
Male	16 (35.6)	40 (54.1)	0.077**
Indications of delivery, n (%)
Clinical chorioamnionitis	8 (17.8)	4 (5.4)	0.153****
Plasental abruption	6 (13.3)	15 (20.3)
Non-reassuring fetal status	5 (11.1)	8 (10.8)
Spontane labor	26 (57.8)	42 (56.8)
34. gestational weeks	-	2 (2.7)
Cord prolapse	-	3 (4.1)
Maternal morbidity, n (%)	11(24.4)	13 (17.6)	0.502**

Benefiting from expectant management: Survival to discharge

Not- benefiting from expectant management: Previable births, stillbirths, deaths in delivery room and neonatal deaths.

Data are given as median (interquartile range), mean (SD^¶, standart deviation) or n (%).

IQR, Interquartile range; BMI, Body mass index; GA, Gestational age; PPROM, Preterm premature rupture of membranes; D&C, Dilatation and Curetage; AFI, Amniotic Fluid Index; WBC, White Blood Cell; CRP, C-Reactive Protein

^µfirst and/or second trimester vaginal bleeding

ð patients whose cervical lenght was <25 mm at admission

*Independent sample t test

** Continuity Correction

***Mann- Whitney U

****Pearson chi-square

***** Fisher’s Exact Test

Table 2: Neonatal characteristics and outcomes of neonatal survivors

	n = 45
GA at delivery^¶ (weeks)	26 (4.5)
Birth weight (grams)^¶	910 (570)
APGAR 5. minute <7	21 (46.7)
Need of NRP	27 (60)
Type of NRP
PPV	13(29)
Intubated	10 (22)
Compression	3 (6.7)
Drugs	1(2.2)
Need of MV	33 (73.3)
Days of ıntubated (IQR)	11.0 (24.5)
Need of Nasal MV	41 (91.1)
Need of HFO	6 (13.3)
Neonatal morbidities
RDS	38 (84.4)
Severe BPD	27 (60)
PDA	26 (57.8)
Cultur proven sepsis	14 (31.1)
ROP stage 3-4	11 (24.4)
NEC stage 2-3	5 (11.1)
PVL	5 (11.1)
Pulmoner hemorrhage	4 (8.9)
Konvulsion	4 (8.9)
Positional deformity	3 (6.7)
IVH grade 3-4	2 (4.4)
Duration NICU stay (days)^¶	73 (5)
Survival to discharge with no major morbidity, n (%)	15 (33.3)
Survival to discharge with at least one major morbidity, n (%)	30 (66.7)

Data are given as median (interquartile range)^¶ or n (%).

GA; Gestational age, NRP; Neonatal Resuscitation Program, PPV; Positive Pressure Ventilation, MV; Mechanical Ventilation, HFO; High Frequency Oscillation, RDS; Respiratory Distress Syndrome, BPD; Bronchopulmonary Dysplasia, PDA; Patent Ductus Arteriosus, ROP; Retinopathy of Prematurity, NEC; Necrotizan Enterocolitis, PVL; Periventricular Leucomalacia, IVH; Intraventricular Hemorrhage, NICU; Neonatal Intensive Care Unit

Table 3: The sensitivity analysis for GA at delivery (weeks), latency period (days), birth weight (gram) and their combination for not-benefiting ekspectant management

Cut-off

Sensitivity (95% CI)

Specificity (95% CI)

PPV (95% CI)

NPV (95% CI)

AUC+-standard error

p

GA at delivery

≤23

51,35 (39,4 - 63,1)

93,33

(81,7 - 98,6)

92,7

(80,6 - 97,5)

53,8

(47,7- 59,9)

0.79± 004

<0.001

Latency period

≤9

71,62

59,9- 81,5

66,67

51,0- 80,0

77,9

69,5- 84,5

58,8

48,5- 68,4

0.71± 005

<0.001

Birth weight

≤640

67,57

55,7- 78,0

82,22

67,9- 92,0

86,2

76,6- 92,3

60,7

51,9- 68,8

0,82+-0.04

<0.001

Combination

>0,4414

90,38 (79,0- 96,8)

50 (33,4- 66,6)

79,2(60,9- 90,3)

0,78+-0.05

<0.001

GA; Gestational age, PPV; Positive predictive value, NPV; Negative predictive value, AUC; Area under curve

No competing interests reported.

Periviable preterm prelabor rupture of membranes: Outcomes of pregnancies following expectant management

Status:

Version 1

Abstract

Figures

Introduction

Material and Methods

Patients

Initial approach

Pregnancy management

Outcomes

Statistical analysis

Results

Benefit from expectant management

Outcomes of neonates

Discussion

Conclusion

Abbreviations

Declarations

References

Tables

Additional Declarations

Status:

Version 1