Could amniotic infusions improve lung development?

An obstructed urinary tract, viewed on fetal ultrasound

Babies whose urinary tracts are obstructed before birth are at risk for a life-threatening complication: being born with poorly developed lungs. But surgeon Grace Nicksa, MD believes lung development could be preserved if the mother’s womb were infused with enough fluid at the right time in her pregnancy.

As a fetus grows, it’s bathed in a protective, liquid blanket of amniotic fluid. In the third trimester of pregnancy, most of this fluid comes from the baby’s own urine, which it both swallows and expels, urinating about a liter a day. The baby also breathes this fluid into its developing lungs, an exercise that works like prenatal pulmonary calisthenics to prepare the lungs for their impending task in the outside world.

In 1 of every 5,000-8,000 live male births, the urinary tract is obstructed by a congenital malformation that leaves the baby unable to urinate, known as posterior urethral valves. “If the fetus can’t pee, you lose the amniotic fluid volume that is normally present — and its benefits,” says Nicksa, in Children’s Department of Surgery.

Surgeons can easily correct this problem after birth, but in the meantime, the low amniotic fluid volume (known as oligohydramnios, visible on a routine prenatal ultrasound at as early as 12-16 weeks) prevents the baby’s lungs from developing properly. The precise reason isn’t clear. One theory is that the lungs are missing exposure to growth factors in the fluid; other theories involve altered fluid dynamics or compression of the lung.

Nicksa, who subscribes to these more mechanical theories, wondered what would happen if the lost fluid were replaced. With her mentor, Terry Buchmiller, MD, co-director of Children’s Advanced Fetal Care Center, Nicksa tested this idea in a large animal model of prenatal urinary obstruction, infusing a solution known as lactated ringer’s into the mother’s womb three times weekly for 4-5 weeks. As Nicksa recently reported at the annual meeting of the American Pediatric Surgical Association (May 19, 2010), animals born to mothers so treated had a higher lung-volume to body-weight ratio than the controls.

Nicksa would now like to develop and test an improved infusion delivery system, since the uterine port used in her experiments is likely to be too bulky for human mothers, and could set off premature labor. “Further work needs to be done to validate our findings in a primate model, determining the ability for mothers to get pregnant afterwards and deliver without any sequelae,” says Nicksa.