There were 512 patients from seven randomized trials included in this sub-study among 1048 AFFIRM patients in the database23–29. Participants from the ETHIG II trial were excluded because no induction data was collected (n = 85)30 and one of the study investigators did not consent the use of individual trial data (n = 113)31. Additional participants were excluded because of missing labor data (n = 22), current pregnancy ending in pregnancy loss (n = 108), and no trial of labor because of elective CD (n = 153) or an unscheduled or emergency CD (n = 55) (Figure 1).
The mean age of participants was 30.3 years old, with a mean of 2.6 pregnancies and 1.0 prior live births reported. Prior pregnancies were complicated by preterm delivery (82.4%), pre-eclampsia (61.3%), placental abruption requiring delivery (29.5%) and SGA neonates < 10th percentile (28.0%) (Table 1). The placenta-mediated pregnancy complications reported in the AFFIRM study pregnancy included pre-eclampsia (6.1%), placental abruption requiring delivery (0.40%) and SGA neonate < 10th percentile (14.5%) (Table 1). Demographic data according to labor type is reported in Table 1. There were 50% of women in the induction of labor group who had a prior pregnancy loss and 28.6% who had a pregnancy loss >20 weeks, compared to 19.8% and 9.0% in the spontaneous labor group, respectively (Table 1). The proportion of participants who underwent induction of labor according to individual trial varied (Table 2).
In the primary analysis, there was no significant difference in the risk of CD between induction of labor (21/148, 14.2%) and spontaneous labor (79/364, 21.7%) (odds ratio (OR) 0.60, 95% CI, 0.35–1.01; p = 0.052) (Table 3). The gestational age at delivery for the induction of labor group was 38.8 weeks gestation, compared to 37.4 weeks gestation in the spontaneous labor group (p<0.01).
Out of 512 participants, 274 (53.5%) were randomized to receive LMWH prophylaxis during pregnancy. The proportion of women who underwent an induction of labor and used LMWH prophylaxis during pregnancy was 29.9% (82/274, 95% CI, 24.81–35.60) compared to 27.7% (66/238, 95% CI, 22.43–33.74) who did not use LMWH. Among the 274 women who used LMWH prophylaxis during pregnancy, the risk of CD was lower among those that underwent an induction of labor (9.8%) compared to spontaneous labor (22.4%) (OR 0.38, 95% CI, 0.17–0.84; p = 0.01). Among the 238 women who did not use LMWH prophylaxis during pregnancy, there was no significant difference in the risk of CD among those that underwent an induction of labor (13/66, 19.7%) compared to spontaneous labor (36/172, 20.9%) (OR 0.93, 95% CI, 0.46–1.88; p = 0.83) (Table 3). The gestational age at delivery was 38.0 weeks in the LMWH group, compared to 37.7 weeks in the no LMWH group (p = 0.26).
There was an increased risk of peripartum major and minor bleeding among women who received an induction of labor compared to spontaneous labor (Table 3). Among women who received LMWH during pregnancy, two (2.5%) had peripartum major bleeding and 11 (13.8%) had peripartum minor bleeding in the induction of labor group, compared to one (0.5%) and one (0.6%) in the spontaneous labor group, respectively (peripartum major bleeding: OR 4.90, 95% CI 0.44–54.79, p = 0.21; peripartum minor bleeding: OR 4.21, 95% CI 1.57–11.31, p = 0.002). Among patients who did not receive LMWH during pregnancy, four (6.2%) had peripartum major bleeding and seven (0.8%) had peripartum minor bleeding in the induction of labor group, compared to one (0.6%) and nine (5.3%) in the spontaneous labor group, respectively (p = 0.02 peripartum major bleeding, p = 0.15 peripartum minor bleeding). There were no postpartum VTE events or maternal mortalities reported. There were six neonatal deaths, one (0.7%) among a woman who received an induction of labor and five (1.4%) with spontaneous labor (Table 3). Of the six neonatal deaths, four were delivered preterm (36 weeks, 34 weeks, 28 weeks and 24 weeks), four were delivered by emergency CD, and all were SGA (1 <3rd percentile; 3 <5th percentile; 2 <10th percentile). Women who delivered these infants had a previous history of pre-eclampsia in four of the cases, and confirmed pre-eclampsia during the current AFFIRM pregnancy in two of the six cases.