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