Key Takeaways
- Anhydramnios due to fetal kidney failure is considered fatal for the neonate due to lethal pulmonary hypoplasia.
- With serial amnioinfusions delivered before the third trimester, 19 of 29 live births survived at least 14 days with dialysis access placement.
- Seven of the 11 infants surviving long term have received a kidney transplant.
Over a third of infants born following pregnancies with anhydramnios due to fetal kidney failure were able to avoid death from underdeveloped lungs with serial amnioinfusions during pregnancy, the nonrandomized RAFT study showed.
Twenty-nine of 32 pregnancies undergoing the intervention resulted in live births, with 19 neonates surviving at least 14 days with dialysis access placement, a result that met the study's primary endpoint, reported Meredith Atkinson, MD, MHS, of the Johns Hopkins University School of Medicine in Baltimore, and colleagues.
Seven of the 11 surviving infants to date have received a kidney transplant, as detailed in JAMA. Without the intervention to restore the amniotic fluid, the expected survival for these neonates is zero given the lethality of pulmonary hypoplasia due to fetal kidney failure.
"This study confirmed that serial amnioinfusions represent a feasible intervention that can alter the fatal prognosis of midtrimester anhydramnios by mitigating pulmonary hypoplasia in most neonates," wrote Atkinson and co-authors. "However, this path is burdened by prematurity and significant long-term morbidity, underscoring the necessity of thorough, nuanced counseling for families considering this intervention."
Survival dropped off over the first few months of life, declining from 58.6% at 30 days to 48% at 90 days. Ultimately, 14 infants survived to hospital discharge at a median age of 4.7 months, but three infants died after discharge. The burden of morbidity among survivors was high: six of the 11 children suffered strokes, including one spinal stroke.
Ongoing ethical consideration around prenatal counseling is warranted, the researchers acknowledged, as a previously lethal fetal diagnosis evolves into one that with the intervention is associated with lifelong end-stage kidney disease (ESKD) and high rates of neurologic morbidity.
The heavy toll was mirrored in quality-of-life data from the study. All families who provided feedback reported worrying about their child's future, and the vast majority reported chronic anxiety. Three-quarters noted that family activities required significantly more time and effort, and most children suffered from low energy.
Atkinson and colleagues emphasized that families must understand the limits of the procedure.
"Prenatal amnioinfusions do not guarantee respiratory survival in all neonates, and the likelihood of respiratory complications (e.g., pulmonary hemorrhage) in survivors should also be reviewed during prenatal counseling," they wrote, noting that stressors like infection or fluid overload could easily trigger a need for advanced respiratory support.
The current analysis involved maternal-fetal pairs with anhydramnios due to fetal kidney failure without bilateral renal agenesis (BRA) and rounds out previously reported results from RAFT on the patient group with BRA.
"Like the BRA group, the proportion of infants surviving to discharge home was smaller than those surviving to the primary outcome, confirming the burden of morbidity and mortality in infants with ESKD from birth," the researchers said.
Screening and enrollment for the open-label, prospective single-arm study ran from 2018 to 2025 at 13 U.S. fetal intervention centers.
The fetal kidney failure cohort counted 34 pregnant individuals (median age 30 years, 27% nulliparous), of whom 32 chose the intervention and two chose expectant management.
The intervention group underwent ultrasound-guided percutaneous amnioinfusions using warmed isotonic solution (with or without antibiotics) under local anesthesia. The procedures began before 26 weeks' gestation to maintain a normal amniotic fluid index.
The intervention appeared safe for mothers, resulting in no unexpected obstetric complications.
Factors significantly associated with neonates reaching the 14-day survival endpoint included:
- Receiving more amnioinfusions: median 14 in survivors vs seven in nonsurvivors
- Longer time interval from first amnioinfusion to preterm prelabor rupture of membranes: 63.5 vs 29 days
- Gestational age greater than 32 weeks: 79% vs 38%
- Higher birth weight: 4.47 vs 3.60 lb
The study's primary limitations included its small sample size and a requirement that participants have adequate insurance coverage at enrollment. Also, postnatal care was not standardized across the trial sites.
"Future research must focus on minimizing preterm delivery, optimizing and standardizing neonatal care, improving long-term survival to long-term dialysis and kidney transplant, and characterizing neurodevelopmental and multidomain health outcomes for infants and families," Atkinson and colleagues urged.