OUTCOMES OF INDUCTION VERSUS SPONTANEOUS ONSET OF LABOUR WHEN PERFORMED AT 40 AND 41 GESTATIONAL WEEKS: FINDINGS FROM A PROSPECTIVE INDIVIDUAL PATIENT DATABASE IN SRI LANKA
Short title: Outcomes of induction of labour from a prospective database, Sri Lanka
Hemantha Senanayake,1,2 Ilaria Mariani,3Emanuelle Pessa Valente,3 Monica Piccoli,4 Benedetta Armocida,3Caterina Businelli,4 Mohamed Rishard,1,2 Benedetta Covi,3 Marzia Lazzerini.3
1 University Obstetrics Unit, De Soysa Hospital for Women, Colombo, Sri Lanka
2 Faculty of Medicine, Department of Obstetrics & Gynaecology, University of Colombo, Colombo, Sri Lanka
3 Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, WHO Collaborating Centre for Maternal and Child Health, Trieste, Italy
4 Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”, Department of Obstetrics & Gynaecology, Trieste, Italy
Authors’ e-mail contacts
HS: senanayakeh@gmail.com
IM: ilaria.mariani@burlo.trieste.it
EPV: emanuelle.pessavalente@burlo.trieste.it
BA: benedetta.armocida@burlo.trieste.it
MP: monica.piccoli@burlo.trieste.it
CB: caterina.businelli@burlo.trieste.it
MR: mrishard@obg.cmb.ac.lk
BC: benedetta.covi@burlo.trieste.it
ML: marzia.lazzerini@burlo.trieste.it
Corresponding author
Ilaria Mariani, MSc
WHO Collaborating Centre for Maternal and Child Health Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”,
Via dell’Istria 65/1, 34137, Trieste, Italy
Ilaria.mariani@burlo.trieste.it
Tel: +39 040 3785 642
List of abbreviations
AOR= Adjusted odds ratio
APH= Antepartum haemorrhage
BMI= Body mass index
CI= confidence interval
CS= Caesarean section
GW= gestational weeks
IOL= Induction of labour
IUGR= Intrauterine growth restriction at ultrasonography
LMIC= Low and middle-income countries
NICE= National Institute for health and Care Excellence
OT= operating theatre
OVD= operative vaginal delivery
PPH= Postpartum haemorrhage
RCT= randomized clinical trial
SGA= Small for gestational age
SOL= Spontaneous onset of labour
STROBE= STrengthening the Reporting of OBservational studies in Epidemiology
UK= United Kingdom
US= United States
WHO= World Health Organization
ABSTRACT WORD COUNT=245/250
ABSTRACT
Objectives The World Health Organization (WHO) recommends induction of labour (IOL) for low risk pregnancy from 41+0 gestational weeks (GW). Nevertheless, in Sri Lanka IOL at 40 GW is common practice. This study aimed to compare maternal/newborn outcomes after IOL versus spontaneous onset of labour (SOL) at 40 GW (IOL40) and 41 GW (IOL41).
Design Observational study.
Setting De Soysa Teaching Hospital for Women, Colombo, the largest maternity hospital in Sri Lanka.
Population Low risk pregnancies at 40 or 41 GW.
Methods Data from a routine prospective individual patient database were analysed. IOL and SOL groups were compared using logistic regression.
Main Outcome Measures Births with one or more negative maternal/newborn outcome/s; maternal/newborn complications; caesarean section (CS); operative vaginal delivery.
Results Of 13670 deliveries, 2359 (17.4%) were singleton and low risk at 40 or 41 GW. Of these, 456 (19.3%) women underwent IOL40, 318 (13.5%) IOL41, and 1585 (67.2%) SOL. Both IOL40 and IOL41 were associated with an increased risk of any maternal/newborn negative outcomes (OR=2.21, 95%CI=1.75-2.77, p<0.001 and OR=1.91, 95%CI=1.47-2.48, p<0.001 respectively), maternal complications (OR=2.18, 95%CI=1.71-2.77, p<0.001 and OR=2.34, 95%CI=1.78-3.07, p<0.001 respectively) and CS (OR=2.75, 95%CI=2.07-3.65, p<0.001 and OR=3.01, 95%CI=2.21-4.12, p<0.001 respectively). Results did not change in secondary and sensitivity analyses.
Conclusions Both IOL groups were associated with higher risk of negative outcomes compared to SOL. These findings, though potentially explained by selection bias, local IOL protocols and CS practices, are valuable for the Sri Lankan context, particularly given contradictory findings from other settings.
TWEETABLE ABSTRACT WORD COUNT=109/110
Tweetable abstract. Induction of labour in low risk pregnancy at 40/41 GW increases risk of negative birth outcomes in Sri Lanka.
Keywords. Induction of labour; Full term pregnancy; Late term pregnancy; Pregnancy outcomes; Low risk pregnancies
MAIN TEXT WORD COUNT = 3474/3500
INTRODUCTION WORD COUNT= 785/400
DISCUSSION AND CONCLUSION WORD COUNT =1067/1200
INTRODUCTION
Over the past decades, induction of labour (IOL) rates have continued to rise, with a reported average incidence of one out of four births at term (from 37+0 GW) in high-income countries, and very similar rates in low and middle-income countries (LMIC)1. According to the World Health Organization (WHO), IOL should be performed only when there is a clear medical indication and the expected benefits outweigh its potential harms2. As perinatal risks increase with gestational age, the current recommendation from WHO, the National Institute for health and Care Excellence (NICE), and most scientific societies is to perform IOL in women who are known with certainty to have reached 41 GW (i.e., from 41+0).3-7
However, especially in the last few years, the debate on optimal timing for IOL and, specifically, whether IOL around term improves birth outcomes, has become very lively. The most recent Cochrane review (2018) including 30 randomized clinical trials (RCTs), seven conducted in southeast Asia, highlighted that IOL from 37 GW compared to expectant management is associated with fewer perinatal deaths, neonatal intensive care unit admissions, babies with low Apgar scores and caesarean sections (CS), but also with more operative vaginal delivery (OVD).8 Authors concluded that further investigation is needed into optimal timing of IOL, together with exploration of women’s risk profiles and preferences.8
More recently, other evidence has emerged. In 2019, a meta-analysis of cohort studies including 15 million pregnancies in high-income countries reported that stillbirth increases slightly but significantly from 37 GW onward with a 64% increase in the risk of stillbirth at 41 GW compared to 40 GW,9 thus suggesting the opportunity of elective IOL even before the traditional cut-off of 41 GW.
Other relevant RCTs were published in parallel. A single-centre RCT in the UK among nulliparous women over 35 years old without complications showed no significant difference in maternal and newborn outcomes between IOL at 39 GW and expectant management.10 More recently, the ARRIVE trial, a multicentre RCT conducted by Grobman et al. among 6106 low-risk nulliparous women in the US compared IOL at 39 GW to expectant management and found lower incidence of CS with IOL (RR 0.84; 95%CI 0.76-0.93) and no significant differences in perinatal deaths or severe neonatal complications (RR 0.80; 95%CI 0.64-1.00).11 A meta-analysis of cohort studies12 confirmed the results of this trial.11
Two other RCTs in uncomplicated singleton pregnancies - INDEX, a Dutch trial enrolling 1801 women,13 and SWEPIS, a Swedish multicentre trial in 14 hospitals including 2760 women14 - found that IOL at 41 GW was associated with fewer adverse perinatal outcomes than expectant management until 42 GW.13,14 Notably, the SWEPIS study was stopped early because of higher perinatal mortality with SOL.14
On the other hand, a national retrospective register-based cohort study evaluating the effects of changes in routine elective IOL policies in Denmark (42 GW versus 41+3 and 41+5 GW) found no differences in neonatal outcomes including stillbirth, despite the number of women with IOL increasing significantly.15 Additionally, a systematic review reported that IOL at 41 versus 42 GW was associated with an increased risk of CS (RR 1.11; 95%CI 1.09-1.14) and adverse maternal outcomes.16
In conclusion, evidence is still contradictory and the debate is quite polarized. No clear context-specific evidence exists on women’s preferences on IOL. The ARRIVE trial reported that American women in the IOL group had a positive perception of increased control over birth,11,17 while other qualitative systematic reviews concluded that the majority of women feared medical intervention, preferring a physiological birth promoting their physical and psychosocial capacities.17, 18
In addition, literature on outcomes of IOL around term versus expectant management in LMIC is very scarce. According to the WHO Global Survey on Maternal and Perinatal Health, IOL was performed in Asia in 12.1% of deliveries and associated with negative neonatal outcomes.19According to existing estimates, Sri Lanka has the highest IOL rate in Asia (about 35.5% of total deliveries)1,19 with 77.2% of all IOL being elective.19 Elective IOL at 40 GW is often justified by local professionals on the basis of supposed earlier foeto-placental maturation in South Asian populations compared with Caucasian women or Asian counterparts, and on the fear of increased risk for the baby.20-22Nevertheless, no study from Sri Lanka has so far explored outcomes of women with IOL at 40 GW versus 41 GW.
The objective of this study was to assess adverse maternal and neonatal outcomes in low risk women undergoing IOL at 40 and 41 GW versus women with a spontaneous onset of labour (SOL) giving birth at the largest maternity hospital in Sri Lanka. Data for this study were collected over four years in a prospective individual patient database established in 2015 at the De Soysa Teaching Hospital for Women, Colombo.
METHODS