Maternal and Perinatal Outcomes Amongst Nulliparous Singleton Pregnancies Electively Induced at 39 Weeks: A Prospective Observational Study

Abstract

Introduction

Given the uncertainty of inducing beyond 39 weeks, we intended to study the maternal and neonatal mortality and morbidity associated with planned elective induction of labour (eIOL) at 39^0/7 to 39^6/7 weeks.

Objectives

To study the maternal and perinatal outcomes, after eIOL, at 39^0/7 to 39^6/7 weeks, amongst nulliparous singleton pregnancies, followed up for the duration of their hospital stay.

Methods

All consecutive nulliparous, singleton gestations, undergoing eIOL, at 39^0/7 to 39^6/7 weeks, with no plan for caesarean section (CS) or contraindication for vaginal delivery were prospectively recruited. The primary outcome studied was the incidence of CS and neonatal intensive care requirement, and the secondary outcomes studied were induction-delivery interval, incidence of chorioamnionitis, postpartum haemorrhage, meconium aspiration syndrome (MAS), APGAR ≤ 7 at 1 min and neonatal mortality.

Results

Amongst the total 304 mothers electively induced at 39^0/7 to 39^6/7 weeks, 80 (26.3%) mothers underwent CS and 48 (15.8%) neonates required intensive care. Fifteen (4.9%) babies required respiratory support at birth. The mean induction-delivery interval was 19 h 42 min ± 10 h. There were 9(3%) cases of PPH and no reported cases of chorioamnionitis. Eleven (3.6%) babies had an APGAR < / = 7 at 1 min and 9 (2.9%) had MAS, but there was no maternal or neonatal mortality.

Conclusion

Induction of labour at 39 weeks in low-risk nulliparous women did not result in a lower frequency of CS or adverse perinatal outcomes.

Introduction

Preterm as well as post-term delivery is associated with significant mortality and morbidity to the child and mother alike. Although obstetricians agree on induction of labour at 41 weeks, there exists an uncertainty beyond 39 weeks of gestation [1]. For nulliparous patients the current evidence, derived mainly from retrospective observational studies, does not allow a clear recommendation with the exception of the recent ARRIVE (A Randomised Trial of Induction Versus Expectant Management) trial [2].

The ARRIVE trial concluded that induction of labour at 39 weeks in low-risk nulliparous women did not result in a significantly lower frequency of a composite adverse perinatal outcome, but resulted in a significantly lower frequency of caesarean section (CS). It could be that the ARRIVE participants were representative of the study population from which they were drawn and their management resulted in low rates of caesarean birth, but the question still remains whether elective induction of labour (eIOL) would yield similar outcomes in other settings like that of ours in South India. Once full term, many authors have recommended induction of labour, in uncomplicated singleton pregnancies, and our institute follows a similar policy. [3–6] We studied the maternal and perinatal outcomes of eIOL amongst nulliparous women in a more pragmatic setting.

Aims and Objectives

To study the maternal and perinatal outcomes at 39^0/7 to 39^6/7 weeks amongst nulliparous singleton pregnancies electively induced in a tertiary care centre.

Methodology

Study Design and Setting

This was a prospective observational study conducted over a period of 18 months (17/10/2019 to 17/04/2021) in a single tertiary care teaching institute, in Kerala, South India, after independent approval from the Institute Ethics Committee and Institutional Review Board (IEC: 42/19/IEC/JMMC&RI). The study was registered under clinicaltrials.gov (NCT04597528).

Inclusion and Exclusion Criteria

Nulliparous women undergoing eIOL at 39^0/7 to 39^6/7 weeks of gestation with a live singleton foetus in a vertex presentation with no contraindication to vaginal delivery were included if they consented to participate in the study. Individuals who had CS planned, with any contraindication for vaginal delivery at the time of recruitment, known major foetal anomaly or with foetal demise were excluded. (Fig. 1).

Fig. 1.

Flow diagram

Sampling

Consecutive sampling of all nulliparous singleton pregnancies meeting the inclusion and exclusion criteria was done till the sample size was met. Based on the proportion of maternal outcome observed in a retrospective review of records conducted in the department of obstetrics and gynaecology in JMMC and RI, with 95% confidence interval and 20% relative allowable error, minimum sample size was calculated as 300 using the formula n = [(z_1–α/2)² × pq]/d²

Method of Data Collection

All patients admitted to the labour room who met the inclusion and exclusion criteria were prospectively enrolled after procuring an informed consent. Consent was obtained anytime from 34^0/7 to 38^6/7 weeks of gestation. Data were procured on a detailed pre-set proforma, entered in real time and safely stored. The data parameters included maternal baseline characteristics and primary and secondary outcome data with specific time frames (69 parameters). The data were abstracted to an excel sheet and later analysed using SPSS software.

Numerical variables are expressed as mean and standard deviation and categorical variables as frequency and percentages. Incidence rates were calculated for the primary and secondary outcomes as appropriate.

Methods

The cervix was examined at the time of admission to assess the consistency, position, dilatation, length and station of the foetus (in relation to the spine). A Bishop’s score was assigned at the initial examination. If indicated mechanical methods of ripening such as extra amniotic saline (EAS) insertion using a Foley catheter were done. For EAS, after the cervix is cleansed with aseptic solution, we insert a 18 Fr Foley catheter through the cervix under direct visualisation with the use of a sterile vaginal speculum. Once the catheter passes the internal os, the balloon is inflated with 60 mL 0.9% NaCl solution, and the other opening of the Foley is connected to 500 ml of a continuous infusion of 0.9% NaCl solution. External end of the catheter is taped to the inner part of one of the thighs. This mechanical method was followed by pharmacological methods like intracervical prostaglandin E2 (PGE2) gels (Cerviprime®) or vaginal inserts (Propess®) or oral prostaglandin E1 (PGE1) 50 µg given for cervical ripening the next day if indicated. At fixed time frames after prostaglandins, ie; 4 h after PGE1 or 6 h after administering PGE2, the cervix was determined to be favourable or not by assessing the Bishop score. Once in active labour, augmentation with 5 IU of oxytocin in 500 ml 0.9% saline and ARM was done to achieve adequate uterine contractions. These women were subsequently assessed by vaginal examination every 4 h for the progress of labour till delivery and followed up for their duration of hospital stay.

Outcome Measurements

The primary maternal outcome of the study was the incidence of CS. The primary perinatal outcomes studied were the need for admission to neonatal intensive care unit (NICU) requiring cardio-respiratory support. Cardio-respiratory support for a neonate was defined as need for cardiopulmonary resuscitation (CPR), invasive mechanical ventilatory care with a definitive airway, high-flow nasal cannula (HFNC) or continuous positive airway pressure (CPAP) ventilation at any time within 24 h of birth.

Secondary maternal outcomes of interest in this study were the induction-delivery interval, incidence of chorioamnionitis (defined as a clinical diagnosis before delivery) and primary postpartum haemorrhage (PPH). Primary PPH was defined as bleeding within 24 h postpartum requiring any blood transfusion, use of two or more uterotonics (other than oxytocin) or need for mechanical or surgical interventions like obstetric hysterectomy, uterine compression sutures, uterine artery ligation, embolization or balloon tamponade. Secondary perinatal outcomes studied included neonatal mortality, APGAR ≤ 7 at 1 min and incidence of meconium aspiration syndrome (MAS).

Results

The mean age of the participants was 24 ± 3.63 (n = 304, 95% CI, 24.1–24.9) years. Majority of the participants (n = 267, 87.8%) were primigravida, and 22 had comorbidities (Table 1).

Table 1.

Population characteristics

Parameter		N	%
Age		24 ± 3.63 years
Gravida
First		267	87.8
Second		34	11.2
Third		3	1.0
Comorbidities
None		282	92.8
Hypothyroidism		8	2.6
Rh incompatibility		6	2.0
Congenital heart disease		3	1.0
Others*		5	1.6
ARM
Liquor not assessed		30	9.9
Clear		258	84.9
MSAF		16	5.3
Oxytocin Used		54	17.8
Labour analgesia
None		201	66.1
	Normal Vaginal delivery	104
	Operative vaginal delivery	45
	LSCS	52
Epidural		54	17.8
	Normal Vaginal delivery	29
	Operative vaginal delivery	12
	LSCS	13
Pentazocine and Promethazine		49	16.1
	Normal Vaginal delivery	19
	Operative vaginal delivery	15
	LSCS	15

Maternal Outcome

Amongst mothers electively induced at 39^0/7 to 39^6/7 weeks (N = 304), 152 (50.0%) underwent full term vaginal delivery, 72 (23.7%) required operative vaginal delivery, and 80 (26.3%) needed emergency LSCS. The indications for CS are given in Table 2.

Table 2.

Indications for caesarean section

Indication for caesarean section	N (%)
Failed induction	33 (41.3%)
Cephalopelvic disproportion	20 (25%)
Arrest of descent	1 (1.2%)
Foetal distress	7 (8.8%)
Failed instrumentation	1 (1.2%)
MSAF	16 (16%)
Cord prolapse	2 (2.5%)
Total	80

Out of the 304 mothers induced, the mean induction-delivery interval was 19 h 42 min ± 10 h (95% CI 18:34–20:50 h). There was no maternal mortality in this study, and none developed any clinical evidence of chorioamnionitis. Nine (3%) mothers had PPH of which 3 mothers required blood transfusion (Table 3). Cervical assessment using the modified Bishop score before induction revealed that all had a score between zero and eight; after induction, all participants had a score more than 3 upto 10 (Fig. 2).

Table 3.

Maternal outcomes

Maternal outcomes	Frequency n(%)
Primary maternal outcomes
Normal vaginal delivery	152 (50%)
Operative vaginal delivery	72 (23.7%)
LSCS	80 (26.3%)
Secondary maternal outcomes
Average induction-delivery interval	19 h 42 min ± 10 h
Chorioamnionitis	0 (0%)
PPH	9 (3%)
	Blood transfusion requirement	3 [33.3%]
	Requiring 2 or more uterotonics (other than oxytocin)	9 [100%]
	Requiring obstetric hysterectomy	0 [0%)]
	Requiring other mechanical or surgical intervention	0 [0%)]

Fig. 2.

Cumulative Bishop score pre- and post-induction

Perinatal Outcomes

Forty-eight out of the 304 babies born (15.8%), required NICU admissions. Of the 48(15.8%) babies who required NICU admissions, 15(4.9%) babies required respiratory support, 11(3.6%) had an APGAR < / = 7, at 1 min, but no babies required CPR at birth and there was no neonatal mortality. Nine babies in this study had MAS. Out of the nine babies, seven had meconium-stained amniotic fluid (MSAF) at ARM (Table 4).

Table 4.

Perinatal outcomes

Perinatal outcomes	Frequency n (%)
Requiring NICU admission	48 (15.8%)
MAS	9 (2.9%)
Respiratory support needed	15 (4.9%)
	CPAP	6 [40]
	HFNC	7 [46.7]
	ETT	2 [13.3]
APGAR < 7 at 1 min	11 (3.6%)
CPR within 24 h of birth	0 (0%)
Perinatal death	0 (0%)

Discussion

Numerous studies have been done to determine an ideal gestational age for induction of labour to improve the maternal and perinatal outcomes. There are no clear recommendations for induction of labour in nulliparous patients. In this study aimed at analysing the outcomes after elective induction at 39^0/7 to 39^6/7 weeks amongst nulliparous singleton pregnancies, there was no significant maternal or neonatal mortality.

Maternal Outcomes

A recent meta-analysis of seven randomised clinical trials (n = 7598), by Saccone et al. (2019), showed that uncomplicated full‐term singleton-induced gestations had similar incidence of CS delivery compared with controls (18.6% vs 21.4%) [7]. In comparison, the CS rate in our study was 26.3%. The major reason why many providers were earlier opposed to elective induction of labour is because the evidence suggested increased rates of CS [8–10]. In our study even though the caesarean rates were not lower, there was no maternal mortality or complications like chorioamnionitis (0%). Women with postpartum haemorrhage (3%) in this study did not require any massive transfusions (0%) or mechanical or surgical interventions (0%). With better maternal team-based approaches to implement post-delivery care pathways, the morbidity associated with CS has decreased over the last decade [11, 12]. Whether elective induction of labour could be considered as a strategy to improve maternal outcomes by making use of the available manpower to the maximum during convenient hours is a question worth exploring in resource-limited settings.

Nearly a quarter of the women induced (23.7%) underwent operative vaginal delivery (OVD) in this study. OVD is beneficial for women because it avoids CS and its associated morbidities [11]. Unfortunately its trend is on a decline in the low- and middle-income countries [13]. A retrospective cohort study of 807 women at term (37^0/7 and 41^6/7-week gestation) from New Jersey, USA, underwent eIOL when compared to women in spontaneous labour and reported a significant increase in the rate of OVD in eIOL group (8.4% vs. 3.6%, p < 0.0001) [14]. It is crucial that OVD is performed by well-trained providers. Patient and physician preference may have a role in the decision-making process regarding method of delivery [13]. The convenient timings and availability of expertise for OVD may necessitate early termination of trial of labour in high-volume centres in resource-limited settings.

The most common indication for CS in our study was failed induction (41.3%). Unfortunately the duration for which the latent phase should continue before terming it ‘failed’ is still a matter of debate [15]. Parameters like patient exhaustion, physician confidence, patient preference and social factors are often less studied to provide a quantitative answer to guide physicians [16]. Failure of practitioners in allowing an adequate trial of labour may also negate the benefits that we expect from appropriately selected candidates undergoing eIOL.

Perinatal Outcomes

The primary perinatal outcome observed was NICU admissions and the need for respiratory support, which was comparable to similar studies in the last decade [2, 6, 17] (Table 5). Electively induced mothers tend to be more closely monitored in the hospital setting. Hospitals in LMIC catering to geographically remote populations, electively planning admission at term could facilitate better monitored maternal and foetal care.

Table 5.

Comparing recent studies on perinatal outcomes at 39 weeks (2015–2021) amongst nulliparous women

	NICU admissions	APGAR < 7 at 5 min	Perinatal death
Grobman et al. [15]	3%	Not reported	0.1%
Walker et al. [17]	2%	3.6%	0%
Miller [6]	6.1%	0%	0%
EIOL39, 2021	4.9%		0%

The hallmark of labour management in the present day should be individualised care for women in labour with the expectation of a safe and successful vaginal delivery, with the ability and facility to intervene with a CS or OVD in the time of need, to minimise maternal and perinatal mortality and morbidity.

Limitations of the Study

Although the hospital in which the study was done caters to a large geographic population, this was a single-centre observational study, which warrants further evaluation in similar settings. From the outset, we did not include a detailed analysis of the different methods of induction and their respective failure rates in our study. This decision was based on our anticipation that the available sample size may not suffice to justify meaningful outcomes across different groups of induction agents. Consequently, this exclusion may limit the comprehensiveness of our findings, as our primary focus was predominantly on the overall outcomes following induction at 39 weeks. Additionally, a comparison of the study population to other groups, like women undergoing eIOL beyond 40 weeks and those undergoing expectant management beyond 39 weeks, should be undertaken to further understand the ideal gestational age for induction of labour in nulliparous singleton pregnancies.

Conclusion

Induction of labour at 39 weeks amongst nulliparous women did not result in a lower frequency of caesarean delivery or NICU admissions. However, there was no serious maternal and perinatal morbidity or mortality. Elective induction of labour could be considered as a comprehensive strategy to improve maternal and perinatal outcomes, by utilising the available manpower to the maximum during convenient working hours in resource-limited settings.

Author Contributions

AS conceived the study. AS, BM, SVA designed the protocol. AS, NB collected the data. AS, SVA did the statistical analysis. AS did the first draft and SVA the subsequent revisions. BM oversaw the conduct of the study. AS, BM, SG, NB, SVA were equally involved in the overall revision in finalising the manuscript.

Declarations

Conflict of interest

There is no conflict of interest amongst the authors. There is no financial relationship with any organisations.

Ethics Approval

The study was independently approved by the Institutional Ethics Committee and Institutional Review Board, 42/19/IEC/JMMC&RI, and the protocol was registered under clincialtrials.gov NCT04597528. All procedures followed were in accordance with the ethical standards of the responsible institutional committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

Informed Consent

Informed consent was obtained from all patients for being included in the study.