Supplementary Material for: Role of heritable and environmental contributions to the development of severe intraventricular hemorrhage in very preterm infants: Results from a multicenter twins cohort study

Introduction: Severe intraventricular hemorrhage (sIVH) remains a significant complication for very preterm infants (VPIs). This study aimed to assess heritable and environmental contributions to sIVH . Methods: A total of 2074 twin pairs born at gestational age <32 weeks with known sIVH status were identified. Three statistical methods were applied, including the Pearson χ2 test, intra-class correlation (ICC), and ACE modeling. Results: Both Pearson’s χ2 test (P =0.224) and ICC analysis (P =0.534) revealed no significant difference after comparing neither, one, or both of the monochorionic and dichorionic twin pairs who developed sIVH. ACE modeling revealed no contribution of heritability to sIVH risk, while the common environmental impacts on sIVH development were 27.9% (95% CI [23.9%, 31.9%] and 72.1% (95% CI [68.1%, 76.1%]), respectively. Assisted conception (aOR 1.45, 95% CI [1.06, 1.97]), inotropes (<3 days) (aOR 1.71, 95% CI [1.22, 2.39]) , invasive mechanical ventilation (<3 days) (aOR 2.38, 95% CI [1.56, 3.64]) and sedations (<7 days) (aOR 2.25, 95% CI [1.55, 2.06]) had contribution to sIVH, while larger gestational age (aOR 0.77 [0.71, 0.85]) and early surfactant administration (≤2 hours）(aOR 0.58, 95% CI [0.42, 0.79]) prevented VPIs from sIVH. Conclusions: We recognized that environmental factors instead of heritability may play major contribution to the development of sIVH. Quality improvement studies focusing on the potential environmental factors to decrease the incidence of sIVH are warranted.