Elianna Constantino who is now four months old, underwent the in-utero procedure at the University of California, San Francisco's (UCSF's) Benioff Children's Hospital four months before birth.
Elianna has alpha thalassemia major, a lethal blood disorder that would not have allowed her to survive to term. The diagnosis was made at week 21 of pregnancy, when a fetal ultrasound revealed an enlarged over-pumping heart due to lack of functional red blood cells carrying oxygen to tissues and vital organs. As the fetus's condition was deteriorating quickly, the doctors gave an in utero blood transfusion and the fetus was enrolled in the trial.
The fetus received a further four blood transfusions and an injection of the maternal haemopoietic stem cells through the mother's abdomen and into the umbilical vein in the umbilical cord. The rationale behind the treatment is that that the mother's stem cells will eventually colonise the fetus’s bone marrow and restart the healthy production of red blood cells. Once born, the baby would then be treated for alpha thalassemia major.
Fetuses with alpha thalassemia major usually die before birth due to an overworked, failing heart and severely affected neural and brain development. Current management of the condition involves fetal blood transfusions every 3-4 weeks, which continue for life after birth, or a childhood stem cell transplant from a matched donor.
But multiple transfusions can lead to a dangerous build-up of iron, while childhood transplantation can lead to rejection and an array of side-effects due to the harsh immune-suppression medication.
A maternal stem cell transplant in utero could bypass these issues – the immune system is underdeveloped and idle, while the mother at the time of pregnancy is the ideal match. Dr Tippi MacKenzie, the lead pediatric and fetal surgeon who performed the procedure said that 'everybody has a perfect donor when they're a fetus, and that's the mum'.
However, this phase I clinical trial is assessing the safety rather than the effectiveness of the treatment. Although Elianna survived the pregnancy she is not cured.
Dr MacKenzie acknowledged that 'it is too early to say how effective the stem cell transplantation will be, but we are encouraged by how well she and her mother have tolerated the treatment'. She also said that 'her healthy birth suggests that fetal therapy is a viable option to offer to families with this diagnosis'.
Commonly, women who carry fetuses with alpha thalassemia major opt to terminate their pregnancies due to the poor prognosis and the chance of a live birth. But if this trial shows positive results, such treatment could be extended to treat this and other haematological conditions.