Doctors can now reach foetuses in womb
Mother and child are the first patients in an experiment that pushes the limits of foetal therapy, combining blood transfusions and bone marrow transplants while the child is still in the womb
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In the three months before she was even born, Elianna Constantino received five blood transfusions and a bone-marrow transplant. All were given with a needle passed through her mother’s abdomen and uterus, into the vein in her umbilical cord.
Elianna, born February 1 with a robust cry and a cap of gleaming black hair, has a genetic disease that usually kills a foetus before birth. The condition, alpha thalassemia major, leaves red blood cells unable to carry oxygen around the body, causing severe anaemia, heart failure and brain damage.
The transfusions in the womb kept her alive, but only treated her illness. The bone-marrow transplant has the potential to cure it. Whether it will succeed is still too soon to tell.
Elianna and her mother, Nichelle Obar, were the first patients in an experiment that pushes the limits of foetal therapy, a field already known for its daring.
If the treatment works, it could open the door to using bone-marrow transplants before birth to cure not just Elianna’s blood disease but also sickle cell anaemia, haemophilia and other hereditary disorders, some so severe that the prenatal diagnosis may lead parents to end the pregnancy.
Bone marrow is considered a potential cure because it teems with stem cells, which can create replacements for cells that are missing or defective as a result of genetic flaws.
“This line of work moves the field of foetal surgery, which currently consists of big operations for anatomic disorders, in a new direction of molecular and cellular therapies given noninvasively,” said Dr Tippi Mackenzie, a pediatric and foetal surgeon who is leading the study at the UCSF Benioff Children’s Hospital San Francisco, part of the University of California, San Francisco.
Obar, 40, and her husband, Chris Constantino, 37, are healthy but learned during her first pregnancy that they are thalassemia carriers. There are several forms of the disease, and worldwide about 100,000 children a year are born with severe cases. Millions of people are carriers, most commonly those from
Asia, the Mediterranean, Africa or the Middle East.
Carriers are generally healthy, but when two have children together, the children are at risk for the disease. Obar’s ancestry is Filipino and Puerto Rican; her husband’s is Filipino. They live in Kilauea, on the Hawaiian island of Kauai.
Their first child, Gabriel, now 3, is healthy. But each child they conceive has a one-in-four chance of being affected, and during Obar’s second pregnancy, her doctors were on the lookout for the disease.
They found it. An ultrasound at 18 weeks showed that Elianna’s heart was twice the size it should have been, and fluid was accumulating around her lungs and other organs. Blood flow through her brain was abnormally rapid, a sign of severe anemia.
Everything pointed toward alpha thalassemia major — the worst form of the disease. Obar’s doctor and genetic counsellor warned her and her husband that their daughter might not survive.
“Her heart was working so hard,” Obar said, with tears in her eyes.
By this point in pregnancy, the second trimester, an affected foetus has little or no working haemoglobin, the molecule that carries oxygen to cells all over the body. Tissues are suffocating, and the heart struggles to compensate.
Some medical references describe the illness as “incompatible with life,” and most foetuses die in the womb from heart failure. The pregnancy may end in miscarriage, and parents may not know why. Many do not know they are carriers.
Sometimes, as the foetus weakens, a phenomenon called mirror syndrome occurs: The mother also becomes ill, with severe high blood pressure and other problems that can kill her unless the pregnancy is ended.
Infants with untreated alpha thalassemia major who somehow survive until birth almost always have severe brain damage from lack of oxygen.
Transfusions into the umbilical cord during pregnancy can save the foetus and may prevent brain damage. The child will then require transfusions every three or