Smoking of ≥10 cigarettes/day showed the strongest association ( β ≥10 cigarettes/day = −0.352, 95% CI −0.648 −0.057, P = 0.019), as reflected by a 0.9-day delay in reaching the final Carnegie stage. Maternal periconceptional smoking represented by the number of cigarettes/day was associated with a slight non-significant delay of the Carnegie stages ( β cigarettes/day = −0.058, 95% CI −0.122 0.007, P = 0.080). Adjustments were made for potential confounders and other covariates.Ī total of 689 singleton ongoing pregnancies were included and 1210 Carnegie stages were determined. To investigate to which extent delayed embryonic morphological development mediated the effect of smoking, contemporary mediation analysis was used. Multiple linear regression models were used to study the association between smoking, fetal growth and birth weight. Regarding first-trimester morphological development, we additionally stratified our findings for mode of conception. Linear mixed models were used to evaluate the association between smoking and the Carnegie stages.

In the absence of fetal morphology classification methods beyond the embryonic period, fetal ultrasound measurements at around 20 weeks’ GA, and birth weight were used to assess fetal growth. Embryonic morphological development as assessed by the Carnegie developmental stages was evaluated using Virtual Reality techniques. Between 7 + 0 and 10 + 3 weeks, GA serial three-dimensional transvaginal ultrasound scans were performed.

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