Keith Earls has been ruled out of Ireland's RBS 6 Nations opener against Wales for personal reasons, team manager Michael Kearney announced on Friday.
Fergus McFadden has been promoted from the bench to outside centre to plug the gap with David Kearney drafted on to the bench.
Earls' partner Edel McGee gave birth to their first child, Ella-Maye, last week only for complications to have arisen.
"Keith has been ruled out due to personal reasons," said Kearney. "Unfortunately his baby has been taken ill and is in hospital as we speak. The nature of the illness is unclear.
"However, I did speak to Keith this morning and he was hopeful and optimistic that the baby would get home some time over the weekend."
Earls had been chosen to replace Brian O'Driscoll in the number 13 jersey after the Ireland skipper was ruled out of the entire Six Nations following shoulder surgery.
Coach Declan Kidney revealed at Wednesday's team announcement that Earls had only been able to take a limited part in training for the past week following the birth of his daughter.
It was hoped the 24-year-old Munster back would return to the Irish camp that night, but concerns over the child's health have resulted in his withdrawal.
"The decision was taken following a conversation between Declan and Keith yesterday," Kearney said.
"It was thought that it was in the best interests of Keith, his partner and their families that Keith remain in Limerick for the weekend."