Overall, our results suggest that individual fetal DIO3 deficiency is the main driver of the severe congenital defects and viability outcomes but that maternal and/or littermate DIO3 deficiency may also contribute to early developmental delays and associated miss of cranial and cardiac developmental milestones in DIO3-sufficent fetuses, possibly by affecting implantation and placental function. This evidence concerns the gene DIO3 and Global developmental delay.