Suboptimal uteroplacental perfusion and fetal nutrition Maternal (preplacental) factors •Hyposxemia (chronic lung disease, high altitude) •Anemia •Smoking, substance abuse (cocaine, methamphetamines) •Malabsorption, poor weight gain •Environmental toxins: air pollution, heavy metals (lead, mercury), perfluorooctanoic acid (PFOA) Placental factors •Maternal vascular malperfusion pathology (infarction, fibrin deposition, chronic abruption) •Fetal vascular malperfusion pathology •Chronic placental inflammation (e.g. villitis of unknown etiology) •Confined placental mosaicism Umbilical cord (postplacental) factors •Increased coiling •Increased cord length •True cord knot •Single umbilical artery •Marginal or velamentous cord insertion Fetal disorders Genetic disorders (chromosomal, micro deletions/duplications, single site mutations, epigenetic disorders) Structural anomalies (e.g. congenital heart disease, gastroschisis) Congenital infections (cytomegalovirus, toxoplasmosis, herpes, rubella, syphilis, Zika virus, malaria) Teratogen exposure (drugs, toxins)