Primary outcomes
The overall incidence of births with one or more negative outcome (including CS and OVD) is reported in Figure 2 . The rate was significantly lower in the SOL group (27.1%, p<0.001), compared to IOL, without significant difference among IOL at 40 GW and IOL at 41 GW (47.1% versus 45.2%, p= 0.609). As further detailed inTable S3 and S4 , the CS rate was significantly higher among women undergoing IOL either at 40 GW (25.4%) or at 41 GW (28.6%) when compared with SOL (10.3%, p<0.001). OVD rate was significantly higher in IOL at 40 GW (7.0%) compared to IOL at 41 GW (2.8%, p=0.010) whereas no significant difference was found with SOL. The proportion of births with complications different from CS and OVD was not significant among groups (p=0.222).
The trend analysis (Figure S1 ) showed an increasing CS rate over semesters in the group with IOL at 40 GW only (trend test p=0.021), whereas OVD rate decreased overall (trend test p=0.016) and in IOL at 40 GW (p=0.036).
Table S4 details the incidence of maternal and neonatal complications by type of labour. Maternal complications, as defined inTable S1 , were more frequent in IOL groups (36.2% and 39.3% in IOL group at 40 GW and 41 GW respectively vs 19.1% in SOL, p<0.001). Postpartum haemorrhage (PPH) was the most frequent complication after CS and OVD (2.6% vs 5.7% vs 1.9% respectively, p=0.001). The incidence of newborn complications was higher in births with IOL at 40 GW when compared to SOL (22.4% vs 13.4%, p<0.001), particularly admissions to Special Care Baby Unit (15.8% in IOL at 40 GW vs 10.7% in IOL at 41 GW vs 8.6% in SOL group, p<0.001). Newborn infections, neurological complications and respiratory distress syndrome were significantly more frequent in the group with IOL at 40 GW than SOL (respectively, 5.0% vs 2.2%, p=0.002; 3.1% vs 1.3%, p=0.009; 2.4% vs 0.9%, p=0.002). Perinatal deaths and stillbirth rates were low across all groups (one stillbirth in IOL at 41 GW and less than five perinatal deaths in each group).
In multivariate analysis (Table 2 ) with SOL as reference and controlling for age, parity, education, BMI and neonatal weight, both IOL groups were positively associated with higher odds of any negative birth outcome (AOR=2.21, 95%CI=1.75-2.77, p<0.001 for IOL at 40 GW and AOR=1.91, 95%CI=1.47-2.48,p<0.001 for IOL at 41 GW), all maternal complications (AOR=2.18, 95%CI=1.71-2.77, p<0.001 for IOL at 40 GW and AOR=2.34, 95%CI=1.78-3.07, p<0.001 for IOL at 41 GW) and CS (AOR=2.75, 95%CI=2.07-3.65, p<0.001 for IOL at 40 GW and AOR=3.01, 95%CI=2.21-4.12, p<0.001 for IOL at 41 GW). IOL at 40 GW was associated with a higher number of neonatal complications (AOR=1.63, 95%CI=1.24-2.16, p<0.001) and IOL at 41 GW was positively associated with maternal complications other than CS or OVD (AOR=1.83, 95%CI=1.19-2.80, p=0.006).
Secondary and sensitivity analyses
IOL at 40 GW was positively associated with increased numbers of negative birth outcomes (AOR=1.95, 95%CI=1.56-2.44, p<0.001), maternal complications (AOR=1.82, 95%CI=1.44-2.30, p<0.001), CS (AOR=2.09, 95%CI=1.60-2.74, p<0.001), and neonatal complications (AOR=1.58, 95%CI=1.21-2.06, p<0.001) when compared with IOL at 41 GW and SOL combined (Table S6 ). No other significant association was found (Table S5 and S6; Figure S2 ).
We explored a sensitivity analysis including women with risk factors for IOL (oligohydramnios, APH and impaired foetal wellbeing), resulting in an additional 4 women eligible for analysis Table S7 ). Results did not differ from the primary analysis (Table S8 ).
DISCUSSION