Novel Amniotic Fluid Enhances Fetal Care Options

Researchers at the Cincinnati Children’s Fetal Care Center have developed a novel artificial amniotic fluid that could reduce inflammation, preserve fetal membrane integrity and support lung development—particularly in fetuses with kidney failure. The fluid also shows promise for improving outcomes in fetoscopic surgery for spina bifida and other conditions.

Braxton Forde, MD, maternal-fetal medicine specialist at the Cincinnati Children’s Fetal Care Center and assistant professor in the University of Cincinnati Department of Obstetrics and Gynecology, and his colleagues recently presented their findings at the Society for Maternal-Fetal Medicine (SMFM) Annual Pregnancy Meeting. They also will publish their findings in the American Journal of Obstetrics and Gynecology.

The team developed a synthetic amniotic fluid that better replicates the physiological properties of natural amniotic fluid—including pH, osmolarity and electrolyte content—to support fetal development during pregnancy and in-utero surgery.

A Lifeline for Fetuses with Kidney Failure

One of the most promising applications of Forde’s research is focused on fetuses with kidney failure who cannot produce urine—the primary contributor to amniotic fluid in the second and third trimesters. Without amniotic fluid, their lungs cannot develop properly, which jeopardizes their survival and respiratory health after birth.

“We’re trying to recreate the natural environment that these babies are missing,” Forde says. “The goal is not just to support them during surgery, but to replace the fluid they aren’t making—to give their lungs a chance to grow.”

During fetal development, the fetus contributes to amniotic fluid by urinating into the sac. This fluid, rich in nutrients and growth factors, helps support lung development, allowing the fetus to “breathe” it in and out. But fetuses with renal agenesis or severe kidney failure can’t produce this fluid, which leads to pulmonary hypoplasia and often fatal outcomes.

“We’ve been using IV fluids like lactated Ringer’s for years, but they’re not made for fetuses. They’re made for adults,” Forde says.

Unlike standard IV fluids, the synthetic amniotic fluid was designed to closely replicate the natural fetal environment, including:

• Nutrient composition tailored to fetal needs
• Fetal-appropriate osmolarity
• Balanced pH levels for optimal tissue compatibility

All of these factors contribute to improved support for fetal development during pregnancy and surgery.

Reducing Inflammation During Fetal Surgery

The synthetic fluid may also reduce inflammation during fetal surgery, which is a significant concern. “Even when we have a great surgical repair and healthy pregnancy outcomes, we almost always see inflammation in the fetal membranes afterward,” Forde says. “That inflammation weakens the membranes and can contribute to preterm birth. It’s one of the biggest barriers we face.”

The team’s new synthetic fluid addresses this issue. The new amniotic fluid, which better mimics the composition of natural amniotic fluid than standard IV solutions typically used during open or minimally invasive fetal surgery, was designed to replace what’s lost during surgery, offering a solution for both inflammation and inadequate lung development in cases of kidney failure.

During fetal surgery, surgeons typically replace the fluid that leaks out with IV fluids like saline or lactated Ringer’s—but those don’t contain the same protective properties as amniotic fluid. “We asked: Could we make something better?” Forde says.

Preclinical Results and Next Steps

In an earlier preclinical study, Forde and his colleagues tested their artificial fluid in human tissue models by exposing fetal membrane samples to saline, lactated Ringer’s, and their custom synthetic fluid.

“When we exposed the membranes to saline or Ringer’s, we saw a dramatic increase in inflammation—specifically, in the release of pro-inflammatory cytokines and reactive oxygen species,” Forde says. “We also saw visible tissue damage under the microscope. But when we used our artificial amniotic fluid, the response was much closer to the control. The inflammation was significantly lower, and the tissue remained healthy.”

The team designed the fluid to match the pH and electrolyte balance of natural amniotic fluid, and they included molecules like glucose and lactate to better simulate the fetal environment. “We tried to recapitulate the environment the fetus naturally lives in rather than just filling the uterus with water,” Forde says.

He is now preparing for the next research phase and hopes that clinical trials are in the near future. “We’ve learned a lot, but we are still in the middle of this research journey,” Forde says. “But we think this could be a step forward in how we support fetal development and reduce inflammation during surgery.”

(Published April 2025)

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