Table 4

Decomposition of the total effect of infertility treatments on the risk of preterm birth into its direct and indirect (ie, mediated through multiple pregnancies) components

CHD	Infertility treatments	Total effect				Direct effect				Indirect effect				Estimated size of the indirect effect (%)
CHD	Infertility treatments	Unadjusted OR*	95% CI	Adjusted† OR*	95% CI	Unadjusted OR*	95% CI	Adjusted† OR*	95% CI	Unadjusted OR*	95% CI	Adjusted† OR*	95% CI	Estimated size of the indirect effect (%)
All CHDs	None	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref
	All methods combined‡	4.7	3.0 to 7.4	4.8	2.8 to 8.0	1.8	1.1 to 2.8	1.7	1.0 to 2.8	2.6	2.0 to 3.5	2.9	2.0 to 4.2	66.9
	IVF±ICSI‡	5.2	2.9 to 9.5	5.2	3.0 to 9.0	1.9	1.1 to 3.1	1.7	1.0 to 3.0	2.8	2.0 to 3.9	3.0	2.1 to 4.2	66.7
Isolated CHD	None	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref
	All methods combined‡	5.4	3.3 to 8.7	5.5	2.9 to 10.2	1.7	1.0 to 2.8	1.7	1.0 to 2.9	3.2	2.3 to 4.4	3.2	2.3 to 4.5	68.1
	IVF±ICSI‡	5.7	3.0 to 11.0	5.9	3.0 to 11.4	1.7	0.9 to 3.3	1.8	0.9 to 3.5	3.3	2.2 to 5.0	3.3	2.2 to 5.1	68.2
Isolated major CHD	None	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref	1.0	Ref
	All methods combined‡	4.6	1.7 to 11.9	3.9	1.5 to 9.9	2.2	0.8 to 6.0	1.8	0.7 to 4.5	2.1	1.3 to 3.5	2.2	1.2 to 3.9	57.7
	IVF±ICSI‡	5.6	1.7 to 18.5	4.5	1.2 to 17.4	2.3	0.7 to 8.1	1.8	0.5 to 6.4	2.5	1.3 to 4.5	2.6	1.4 to 4.6	62.7

*ORs represent the odds of preterm birth in fetuses with CHD exposed to ART relative to the odds of preterm birth in fetuses with CHD unexposed to ART.
†Adjusted for maternal sociodemographic characteristics (age, geographical origin, occupation), gravidity, diabetes mellitus, vaginal bleeding, invasive prenatal testing, prenatal diagnosis of CHD, intrauterine growth restriction, medical induction of labour or caesarean delivery before labour and year of birth.
‡Including induction of ovulation.
ART, assisted reproductive technique; CHD, congenital heart defect; ICSI, intracytoplasmic sperm injection; IVF, in vitro fertilisation; Ref, reference.