Intentional delivery versus expectant management in preterm prelabour rupture of membranes at 28–34 weeks of gestation

Abstract

Background

Preterm prelabour rupture of membrane (PPROM) often precedes a significant number of preterm deliveries. However, the optimal timing of delivery in women with PPROM remains unclear.

Objective

To compare duration of neonatal intensive care between two management strategies – intentional delivery and expectant delivery, in women with PPROM between 28 and 34 weeks of gestation. Additionally, we also compared other crucial neonatal and maternal outcomes between the two groups.

Materials/method

This prospective observational study enrolled women aged over 18 years; singleton pregnancy complicated by PPROM occurring between 28 and 34 weeks of gestation. These women were managed either by intentional delivery (ID) or expectant management (ED), as per clinician discretion.

Result

A total of 115 women were included in the study; 68 women underwent intentional delivery and 47 women by expectant management. Neonates born to mothers in the ID group had a significantly shorter hospital stay compared to those in the ED group (12.71 ± 13.89 vs. 20.02 ± 20.94, Mean difference 7.3 days, 95% CI: −0.9 to −13.7 days, p 0.026). The early onset neonatal sepsis was similar [11 (16.2%) in the ID group and 9 (19.1%) in the ED group, p 0.688 and other neonatal and maternal outcomes were also comparable between the two groups.

Conclusion

In intentional management, the duration of neonatal hospital stay was shorter in comparison to the expectant management group, while there was no difference in other maternal and major neonatal outcomes. There was a clinician preference for expectant delivery with lower foetal weight.

Keywords

expectant management intentional delivery premature rupture of membrane preterm

Introduction

Preterm prelabour rupture of membranes (PPROM) occurs in 1%–5% of all pregnancies and accounts for approximately 20%–55% of preterm deliveries.^1,2 Management of pregnancy complicated by PPROM remains a challenge for obstetricians. Two main approaches include immediate delivery and conservative management. While conservative management may prolong pregnancy, it also elevates the risk of neonatal sepsis and subsequent complications, whereas earlier induction of labour increases the risk of prematurity and associated issues.² Furthermore, 2%–5% of PPROM cases may be complicated by placental abruption.³

The American College of Obstetricians and Gynecologists (ACOG) recommends either expectant management or delivery (via induction or caesarean) after 34 weeks of gestation.⁴ However, the optimal timing for delivery in cases of PPROM before 34 weeks remains uncertain with guidelines suggesting towards expectant management.⁴ Studies with women with PPROM between 24 and 34 weeks of gestation have provided different results. DOMINOS study showed active management to be associated with decreased risk of adverse neonatal outcomes⁵ while a multicentric trial from 19 tertiary care hospitals in France, and Switzerland found no significant difference in neonatal mortality or serious adverse events between conservative management.⁶

Thus, with aim to address the optimal timing, we aimed to compare the neonatal and maternal outcomes in women with PPROM between 28 and 34 weeks of gestation managed by intentional delivery or expectant management.

Materials and methods

Study design, settings, and participants

The study is a prospective comparative observational study conducted in 1000 bed tertiary care hospital in eastern India from January 2020 till June 2021. Women aged 18 years and above who presented with PPROM and a singleton pregnancy of 28–34 weeks’ gestation were included in the study. Multiple pregnancies, women with chorioamnionitis at admission, hypertensive diseases of pregnancy, and placental abruption were excluded.

Intervention

Two management strategies for PPROM were followed − intentional delivery (ID) and expectant management (ED) as per the treating obstetrician. In intentional delivery group, the women with confirmed PPROM were delivered either by induction of labour or caesarean section 24 hours after second dose of steroid. The mode of delivery was left to the discretion of the attending obstetrician, depending on obstetric and foetal indications. Whereas in the expectant management, the women advised for bed rest with regular check for signs of fever and vitals monitoring. They were also tested for infection markers like total white blood cell count and C-reactive protein. These women also had electronic foetal monitoring performed twice a day and biophysical profile assessment every alternate day. Prophylactic antibiotic therapy was given for 5 days. Prolongation beyond 96 hours was left to the discretion of the attending obstetrician. All mothers received two doses of 12 mg betamethasone 24 hours apart and nifedipine as a tocolytic agent was considered till completion of betamethasone dosage.

Management protocol

Gestational age was determined from the date of the last menstrual period (LMA) and confirmed using the first-trimester ultrasound (USG) report. Differences are found in gestation of more than 7 days between LMA and USG, and then USG performed within 16 weeks was considered. The clinical diagnosis of membrane rupture was based on a history of amniotic fluid leakage, with a sterile speculum examination confirming amniotic fluid drainage from the cervical OS. All eligible participants were treated after obtaining written informed consent as follows: A sterile speculum examination was conducted to check for pooling of liquor, a high vaginal swab sample was taken for culture sensitivity testing, and urine routine microscopy and culture sensitivity tests were sent. Vital signs were monitored every 8 hours, and all relevant maternal laboratory tests, such as complete blood count including total leucocyte count and C-reactive protein, were performed. Periodic electronic foetal monitoring was conducted to detect uterine activity and signs of foetal distress, along with a foetal biophysical profile at admission. Prophylactic antibiotic therapy (oral erythromycin 250 mg every 6 hourly) was administered. However, if women who were in the conservative group, the management was discontinued, and delivery was expedited if the attending physician noted any of the following: onset of labour, chorioamnionitis⁷ (maternal intrapartum fever and one or more of the following: maternal leucocytosis, purulent cervical drainage, or foetal tachycardia), non-reassuring foetal status,⁸ or cord prolapse.

Outcome assessment

The primary outcome was the duration of NICU stay of neonates. Secondary neonatal outcomes included birth weight, the need for NICU admission, respiratory distress requiring respiratory support and surfactant administration, culture-proven sepsis, patent ductus arteriosus requiring treatment, intraventricular haemorrhage ≥2 on cranial ultrasound,⁹ necrotizing enterocolitis stage 2 or beyond,¹⁰ retinopathy of prematurity requiring treatment,¹¹ and neonatal hyperbilirubinemia requiring phototherapy. Maternal secondary outcomes comprised the need for emergency caesarean section, clinical chorioamnionitis, endometritis, lactation failure, and duration of hospital stay.

Sample size calculation

In the study by Van der Ham et al,¹² which included infants born before 37 weeks, the mean (SD) NICU stay was 4.1 (4.1) days in the expectant management group and 8.1 (7.9) days in the intentional management group, with an estimated effect size of 0.6355. Using an alpha error of 5% and a study power of 80%, a minimum of 40 infants per group would be required.

Statistical analysis

The data was compiled using Microsoft Excel. Data was presented using descriptive statistics. Mean (standard deviations (SD)) or median (interquartile range (IQR)) were calculated as appropriate for continuous variables. Student t test or Mann−Whitney U test was used to compare continuous variables. For categorical variables, the Chi-square test was used. Any p-value less than 0.05 was considered as significant. Statistical analysis was carried out using SPSS version 21.0.

Ethics

The trial was approved by the institutional ethics committee (DMR/IMS-SH/SOA/180398). Written informed consent was taken from all the participating women prior to enrolment.

Results

The mean (SD) maternal age was 28.2 (4.1) years in the ID group and 28.4 (4.1) years in the ED group (p = 0.90). In the ID group, 39 (56.5%) were primigravida, compared to 26 (55.3%) in the ED group (p = 0.90) (Table 1). The mean (SD) gestational age at PPROM onset was 31.8 (1.8) weeks in the ID group and 31.2 (2.5) weeks in the ED group (p = 0.14). The average time from PPROM onset to delivery was 1.78 (0.98) days in the ID group and 8.98 (6.35) days in the ED group (p < 0.01). Mean gestational age at delivery was 31.88 (1.88) weeks in the ID group and 32.72 (2.52) weeks in the ED group (p = 0.043) (Table 1).

Table 1.

Baseline characteristics.

	Intentional delivery (ID) (n = 69)	Expectant delivery (ED) (n = 47)	p value
Maternal age (years)
• Less than 20	1 (1.4%)	2 (4.3%)	0.33
• 20–30	50 (72.5%)	33 (70.2%)	0.79
• More than 30	18 (26.1%)	12 (25.5%)	0.94
Primigravida^a	39 (56.5%)	26 (55.3%)	0.90
POG at PPROM^a	31.8 ± 1.8	31.2 ± 2.5	0.14
POG at delivery^a	31.88 ± 1.88	32.72 ± 2.52	0.043
AFI before leaking^a	12.62 ± 2.28	12.77 ± 2.39	0.73
Leaking to delivery (days)^a	1.78 ± 0.98	8.98 ± 6.35	<0.01
Fever	7 (10.1%)	11 (23.4%)	0.053
Pregnancy induced hypertension	3 (4.3%)	0 (0%)	0.15
Gestational diabetes mellitus	3 (4.3%)	4 (8.5%)	0.35
Hypothyroidism	6 (8.7%)	11 (23.4%)	0.029
Previous caesarean section	9 (13.0%)	2 (4.3%)	0.12
Intra uterine growth restriction	2 (2.9%)	0 (0%)	0.24
High vaginal swab culture	9 (13.0%)	7 (14.9%)	0.77

Abbreviations: POG – period of gestation, PPROM – preterm prelabour rupture of membrane , AFI – amniotic fluid index.

Variables expressed as n (%) unless specified otherwise.

^aMean (SD).

Maternal fever occurred in 7 (10.1%) of the ID group and 11 (23.4%) of the ED group (p = 0.053). Caesarean section was performed in 40 (58.0%) of the ID group and 27 (57.4%) of the ED group (p = 0.96). Clinical chorioamnionitis was observed in 7 (10.1%) of the ID group and 11 (23.4%) of the ED group (p = 0.053) (Table 2).

Table 2.

Comparison of neonatal and maternal outcomes.

	Intentional (n = 68)	Expectant (n = 47)	p value
Neonatal outcomes
Admission to NICU	58 (84.1%)	40 (85.1%)	0.709
Birth weight (gm)^a	1.740 ± 0.40	1570 ± 0.42	0.033
Gestational age (weeks)^a	31.88 ± 1.8	32.72 ± 2.5	0.043
Respiratory distress	33 (48.5%)	25 (53.2%)	0.622
Culture-positive sepsis	11 (16.2%)	9 (19.1%)	0.688
PDA requiring treatment	3 (4.4%)	1 (2.1%)	0.513
IVH >2	1 (1.5%)	0 (0%)	0.401
ROP requiring treatment	1 (1.5%)	3 (6.4%)	0.162
NNH Requiring phototherapy	32 (34.1%)	26 (55.3%)	0.024
Duration of hospital stay (days)^b	8 (4–14)	9 (6–31.5)	0.026
Maternal outcomes
Need for emergency LSCS	40 (58.0%)	27 (57.4%)	0.955
Clinical chorioamnionitis	7 (10.1%)	11 (23.4%)	0.053
Endometritis	9 (13.2%)	7 (14.9%)	0.82
Lactation failure	12 (17.6%)	4 (8.5%)	0.167

Abbreviations: NICU – neonatal intensive care unit, gm – grams, wks – weeks, PDA - patent ductus arteriosus, IVH – intraventricular haemorrhage, ROP – retinopathy of prematurity, NNH – neonatal hyperbilirubinemia, LSCS – lower segment caesarean section.

Variables expressed as n (%) unless specified otherwise.

^aMean (SD).

^bMedian (IQR).

A total of 98 neonates required NICU admission: 58 (84.1%) in the ID group and 40 (85.1%) in the ED group (p = 0.71). The mean (SD) birth weight was 1740 (400) g in the ID group and 1570 (420) g in the ED group (p = 0.033). Neonatal sepsis rates were similar between groups, occurring in 11 (16.2%) of the ID group and 9 (19.1%) of the ED group (p = 0.69). Rates of respiratory distress syndrome, PDA requiring treatment, and IVH > Grade 2 were comparable between the groups. The median (IQR) duration of hospital stay was 8 (4–14) days in the ID group and 9 (6–31.5) days in the ED group (p = 0.026).

Discussion

Our prospective study aimed to evaluate the impact of delivery timing in pregnancies complicated by PPROM between 28 and 34 weeks of gestation, on the duration of neonatal hospital stay. We found that neonates in the intentional delivery group had a significantly shorter hospital stay of 7.3 days compared to those in the expectant management group.

Previous trials on the management of PPROM between 28 and 34 weeks have yielded conflicting results. A prior meta-analysis of seven clinical trials failed to show a clear benefit of expectant management over immediate delivery. These trials were underpowered and exhibited significant heterogeneity due to the inclusion of varying gestational age.¹³ However, a Cochrane review that incorporated five additional trials suggested that conservative management is generally safe for both mothers and neonates, with lower rates of caesarean sections and neonatal complications.¹⁴ Nevertheless, the review also noted a lower incidence of chorioamnionitis with active management.

Our study primarily focused on how these two management strategies (intentional and expectant) affect neonatal outcomes. In our study, clinicians often preferred intentional delivery, which led to more mothers being delivered immediately during the study period. This variation in practice highlights the lack of definitive evidence to guide the optimal management approach in PPROM. The average gestational age at delivery in the intentional delivery group was 32.7 weeks, 8.9 days longer than in the expectant group. In comparison to MICADO trial, the mean latency from PPROM to delivery was 11.7 days in expectant management group with a mean difference of around 9 days compared to active management group.⁶

Nearly 85% of the infants in both groups were admitted to the NICU. There was no difference in the NICU admission despite the differences in gestational age at delivery. Higher birth weight was seen in the intentional group, suggesting a potential selection bias, as obstetricians may have preferred expectant management for babies with lower birth weights at the time of maternal admission. Furthermore, many neonates in the expectant group had very low birth weights (<1500 grams). This discrepancy in the birth weight also explains the shorter duration of NICU in the ID group. The length of hospital stay was lower in the expectant management group in the MICADO trial.⁶ Babies in the expectant management group had a higher birth weight and the mean gestational age at delivery was higher by a week. The trial could recruit only 40% of the calculated sample size and was terminated due to difficulty in recruitment. In PPROMEXIL trial, women with PPROM between 34 and 37 weeks were included and the neonatal outcome following induction of labour (IoL) and expectant management (EM) were compared. There was no difference in length of hospital stay between the two groups.¹²

A key factor influencing management decisions in cases of PPROM is the concern about neonatal sepsis, driven by the risk of infection associated with prolonged pregnancies. However, in our study, there was no significant difference in the incidence of culture-positive neonatal sepsis between the two groups. This finding aligns with the Cochrane review, which analysed seven studies and found no difference in the rates of culture-positive neonatal sepsis between expectant and intentional management approaches.¹⁴

Respiratory distress syndrome is a major morbidity in preterm neonates. In our study, 53.2% of neonates in the expectant management group developed RDS, compared to 48.5% in the intentional delivery group. Three neonates in the intentional group required surfactant therapy, while only one baby in the expectant group did. All four of these babies were ≤30 weeks’ gestation. This suggests that extending pregnancy beyond 30 weeks may reduce the need for surfactant therapy in cases of RDS. Similarly, two RCTs from the Netherlands (PPROMEXIL and PPROMEXIL 2) found no significant difference in the incidence of RDS between the groups.^12,15

In our study, maternal outcomes were comparable between the groups, with a slightly higher incidence of fever in the expectant group. Caesarean section rates were similar. There was a non-significant trend towards increased chorioamnionitis in the ED group. This finding is similar to the result from the meta-analysis, which suggest lower incidence of chorioamnionitis with planned early delivery.¹³ Data from randomized controlled trials suggest that induction of labour reduces the incidence of chorioamnionitis, while expectant management increases the need for postpartum antibiotics.^12,15,16

Our study has several strengths. First, the prospective design allows for more accurate data collection and improves the validity of study results. Second, the pragmatic nature of the intervention ensures its applicability to a well-equipped tertiary care hospital with a level III NICU. However, the trial also has a few limitations. First, the non-randomized design introduces the risk of selection bias, which could influence the outcomes. The type of intervention in individual cases was left to the clinician. The nature of the study precludes any informed decision from the investigators to the treating clinician and might have resulted in unequal distribution of confounding factors. Second, the lack of prolonged follow-up limits our ability to evaluate the impact on long-term outcomes. Third, the latency period between PPROM and delivery was within 14 days, so the effect of prolonging the pregnancy beyond 14 days could not be assessed in our study. Finally, the inclusion of a broad gestational age range from 28 to 34 weeks may introduce heterogeneity, making it more challenging to draw definitive conclusions about the optimal management strategy for this gestational period.

Conclusion

We can conclude that intentional delivery may be associated with a shorter duration of hospital stay without affecting other major neonatal and maternal outcomes. There was a clinician preference for expectant delivery with lower foetal weight, which might have affected the final result of the study. We suggest an adequately powered randomized controlled study design, which can avoid selection bias and provide a better conclusion about the outcome.

Footnotes

ORCID iDs

Srishty Mohanty

Debasish Nanda

Statements and declarations

Author contribution

SM: Conceptualized, designed the study and collected data. SN: Conceptualization and critical input in preparation of draft. DN: Analysed data and prepared the initial draft. VK: Critical analysis and Revision of the draft.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Conflicting interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Appendix

References

Mercer

Goldenberg

Meis

, et al. The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 2000; 183(3): 738–745. DOI: 10.1067/mob.2000.106766.

Lee

Silver

. Etiology and epidemiology of preterm premature rupture of the membranes. Clin Perinatol 2001; 28(4): 721–734. DOI: 10.1016/s0095-5108(03)00073-3.

Major

de Veciana

Lewis

, et al.

Preterm premature rupture of membranes and abruptio placentae: is there an association between these pregnancy complications?

Am J Obstet Gynecol 1995; 172(2 Pt 1): 672–676. DOI: 10.1016/0002-9378(95)90591-x.

ACOG Practice Bulletin No. 188: Prelabor rupture of membranes. Obstet Gynecol 2018; 131(1):e1-e14. DOI: 10.1097/aog.0000000000002455.

Pasquier

Rabilloud

Picaud

, et al. A prospective population-based study of 598 cases of PPROM between 24 and 34 weeks’ gestation: description, management, and mortality (DOMINOS cohort). Eur J Obstet Gynecol Reprod Biol 2005; 121(2): 164–170. DOI: 10.1016/j.ejogrb.2004.12.015.

Pasquier

Claris

Rabilloud

, et al. Intentional early delivery versus expectant management for preterm premature rupture of membranes at 28-32 weeks’ gestation: a multicentre randomized controlled trial (MICADO STUDY). Eur J Obstet Gynecol Reprod Biol 2019; 233: 30–37. DOI: 10.1016/j.ejogrb.2018.11.024.

ACOG Clinical Practice Update . Update on criteria for suspected diagnosis of intraamniotic infection. Obstet Gynecol 2024; 144(1):p e17-e19. DOI: 10.1097/AOG.0000000000005593.

Ayres-de-Campos

Spong

Chandraharan

, et al. FIGO intrapartum fetal monitoring expert consensus panel. FIGO consensus guidelines on intrapartum fetal monitoring: cardiotocography. Int J Gynaecol Obstet 2015; 131(1): 13–24. DOI: 10.1016/j.ijgo.2015.06.020.

Papile

L-A

Munsick-Bruno

Schaefer

. Relationship of cerebral intraventricular hemorrhage and early childhood neurologic handicaps. J Pediatr 1983; 103(2): 273–277.

10.

Bell

Ternberg

Feigin

, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187(1): 1–7. DOI: 10.1097/00000658-197801000-00001.

11.

The international classification of retinopathy of prematurity revisited. Arch Ophthalmol 2005; 123(7):991–999. DOI: 10.1001/archopht.123.7.991.

12.

van der Ham

Vijgen

Nijhuis

, et al. Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial. PLoS Med 2012; 9(4): e1001208. DOI: 10.1371/journal.pmed.1001208.

13.

Buchanan

Crowther

Levett

, et al. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks’ gestation for improving pregnancy outcome. Cochrane Database Syst Rev 2010; 3: Cd004735. DOI: 10.1002/14651858.CD004735.pub3.

14.

Bond

Middleton

Levett

, et al. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks' gestation for improving pregnancy outcome. Cochrane Database Syst Rev 2017; 3(3): Cd004735. DOI: 10.1002/14651858.CD004735.pub4.

15.

van der Ham

van der Heyden

Opmeer

, et al. Management of late-preterm premature rupture of membranes: the PPROMEXIL-2 trial. Am J Obstet Gynecol 2012; 207(4): 276.e1. DOI: 10.1016/j.ajog.2012.07.024.

16.

Morris

Roberts

Bowen

, et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet 2016; 387(10017): 444–452. DOI: 10.1016/s0140-6736(15)00724-2.

Intentional delivery versus expectant management in preterm prelabour rupture of membranes at 28–34 weeks of gestation – A prospective observational study

Abstract

Background

Objective

Materials/method

Result

Conclusion

Keywords

Introduction

Materials and methods

Study design, settings, and participants

Intervention

Management protocol

Outcome assessment

Sample size calculation

Statistical analysis

Ethics

Results

Discussion

Conclusion

Footnotes

ORCID iDs

Statements and declarations

Author contribution

Funding

Conflicting interest

Appendix

References