Assisted reproductive technology and perinatal outcomes: conventional versus discordant-sibling design

To compare risks of adverse perinatal outcomes between assisted reproductive technology (ART) and naturally conceived singleton births using a dual design approach.

Discordant-sibling and conventional cross-sectional general population comparison.

Not applicable.

All singleton live births, conceived naturally or via ART.

None.

Birth weight, gestational age, low birth weight, preterm delivery, small for gestational age (SGA), low Apgar score.

A total of 32,762 (0.8%) of 3,896,242 singleton live births in the three states were conceived via ART. In 6,458 sibling pairs, ART-conceived singletons were 33 g lighter (adjusted β = -33.40, 95% confidence interval [CI], -48.60, -18.21) and born half a day sooner (β = -0.58, 95% CI, -1.02, -0.14) than singletons conceived naturally. The absolute risk of low birth weight and preterm birth was 6.8% and 9.7%, respectively, in the ART group and 4.9% and 7.9%, respectively, in the non-ART group. The odds of low birth weight were 33% higher (adjusted odds ratio [aOR] = 1.33; 95% CI, 1.13, 1.56) and 20% higher for preterm birth (aOR = 1.20; 95% CI, 1.07, 1.34). The odds of SGA and low Apgar score were not significantly different in both groups (aOR = 1.22; 95% CI, 0.88, 1.68; and aOR = 0.75; 95% CI, 0.54, 1.05, respectively). Results of conventional analyses were similar, although the magnitude of risk was higher for preterm birth (aOR, 1.51; 95% CI 1.46, 1.56).

Despite some inflated risks in the general population comparison, ART remained associated with an increased likelihood of low birth weight and preterm birth when underlying maternal factors were kept constant using discordant-sibling comparison.