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.

  • Patricia

    Could amniotic infusion help an infant with Potters syndrome (BRA) ?

    • nansona

      Hi, Patricia, I checked with one of our physicians and the answer is yes, but she also said that it does not have an effect on kidney function and would likely lead to a preterm delivery. It has been done in for quite a while in small numbers of cases. Here is a recent publication on it:

      Obstet Gynecol. 2014 Aug;124(2 Pt 2 Suppl 1):413-5. doi: 10.1097/AOG.0000000000000339.
      Successful in utero intervention for bilateral renal agenesis.
      Bienstock JL1, Birsner ML, Coleman F, Hueppchen NA.

      Abstract

      BACKGROUND:

      We report a case of bilateral renal agenesis treated with serial amnioinfusion in which the newborn survived the newborn period and was able to undergo peritoneal dialysis as a bridge to planned renal transplantation.

      CASE:

      A 34-year-old woman, gravida 1 para 0, presented at 23 1/7 weeks of gestation with a diagnosis of anhydramnios and bilateral renal agenesis. The patient underwent weekly serial amnioinfusion with the goal of improving fetal pulmonary development. At 28 weeks of gestation, the patient delivered a live newborn who required minimal respiratory support. The neonate is currently 9 months old and is undergoing daily peritoneal dialysis.

      CONCLUSION:

      Serial amnioinfusion appears to have mitigated the severe pulmonary compromise that has, in the past, led to the death of newborns with bilateral renal agenesis.

      I hope this helps!
      Nancy Fliesler, Vector editor

      • Patricia

        Thank you very much for your reply. We were aware of Dr. Beinstock’s findings and as of just yesterday, we traveled to Johns Hopkins to meet with Dr. Beinstock’s group in hopes of meeting the criteria for her studies. Unfortunately, due to the presence of undefined, necrotic renal tissue, we did not meet the criteria for the weekly amnioinfusions….and a chance of survival for our sweet baby boy, Nathan Michael who has three big brothers anxiously awaiting his birth. Thank you again for your response. We appreciate your time. Hopefully, some day, we can fix the outcome for our Potters Syndrome Angels. Thank you for the timeless hours you spend studying in your labs. Those who may benefit from your outcomes are most grateful for your sacrifices.