Assisted Reproductive Technology and Perinatal Outcomes: Conventional versus discordant sibling design

Objective: To compare risks of adverse perinatal outcomes between Assisted Reproductive Technology (ART) and naturally conceived singleton births using a dual design approach. Study design: Discordant sibling and conventional cross-sectional general population comparison. Setting: National ART Surveillance System from Michigan, Massachusetts and Florida (2000-2010) linked to birth records. Patients: all singleton live births, conceived naturally or via ART Interventions: None Main outcome measures: Birthweight, gestational age, low birthweight, preterm delivery, small-for-gestational age (SGA), low Apgar score. Results: 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 33g 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% in the non-ART group respectively. The odds of low birthweight 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 the 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 pre-term birth (aOR 1.51, 95% CI 1.46, 1.56). Conclusion: Despite some inflated risks in the general population comparison, ART remained associated with increased likelihood of low birthweight and preterm birth when underlying maternal factors were kept constant using discordant-sibling comparison.