Jena L. Miller, Ahmet A. Baschat, Anthony Johnson, Yair J. Blumenfeld, Mauro H. Schenone, Juliana S. Gebb, Julie S. Moldenhauer, Michael V. Zaretsky, Ramen H. Chmait, Juan M. Gonzalez, Russel S. Miller, Eyal Krispin, Alireza Shamshirsaz, Katherine H. Bligard, Amanda M. Kalan, Magdalena Sanz Cortes, Anita J. Moon-Grady, Ellen Bendel-Stenzel, Shina Menon, Cynthia Wong, Paul Grimm, Cecilia Kwak, Jacqueline Gallup, Kristin J. McKenna, Leah Marron, Christian Hanna, Cheryl L. Tran, Nicholas J. Behrendt, Henry L. Galan, Joshua Samuels, Rita Swinford, Amaris M. Keiser, Mara Rosner, Michelle L. Kush, Isam Nasr, Samhita Vasu, Renee D. Boss, Angie C. Jelin, Richard E. Thompson, Jonathan M. Davis, Daniel S. Warren, Daniel F. Hanley, Meredith A. Atkinson
Children’s Hospital of Philadelphia. Johns Hopkins University. University of Texas Health Center. Stanford University School of Medicine. Mayo Clinic. Nemours Children’s Hospital. Children’s Hospital Colorado and University of Colorado School of Medicine. University of Southern California, Keck School of Medicine. University of California, San Francisco. Columbia University Irving Medical Center. Boston Children’s Hospital and Harvard Medical School. Dell Medical School of the University of Texas at Austin. Washington University in St. Louis School of Medicine. Cleveland Clinic Foundation. Baylor College of Medicine. AdventHealth Sebring. McGovern Medical School at UTHealth Houston. Yale Medicine and Yale New Haven Children’s Hospital. Yale Medicine, Yale New Haven Children’s Hospital.
United States
Journal of the American Medical Association
JAMA 2026;
DOI: 10.1001/jama.2026.8568
Abstract
Importance: Anhydramnios from fetal kidney failure causes lethal pulmonary hypoplasia. Serial amnioinfusions have shown promise in mitigating pulmonary disease from bilateral renal agenesis, but efficacy and safety for other causes of fetal kidney failure are unproven.
Objective: To assess the efficacy of serial amnioinfusions initiated before 26 weeks’ gestation to mitigate lethal pulmonary hypoplasia in cases of anhydramnios due to fetal kidney failure.
Design, setting, and participants: Prospective, nonrandomized clinical trial conducted at 13 US fetal therapy centers from December 2018 to February 2025. Outcomes for maternal-fetal pairs with anhydramnios before 22 weeks’ gestation due to fetal kidney failure without bilateral renal agenesis are reported; data collection for surviving infants continued until February 13, 2026.
Exposure: Thirty-two participants underwent serial amnioinfusions with isotonic fluid beginning before 26 weeks’ gestation.
Main outcomes and measures: The primary end point was neonatal survival for 14 days or longer with dialysis access placement. Secondary outcome measures of survival to discharge home and kidney transplant are reported.
Results: Twenty-nine of 32 participants (91%) had a live birth, with a median (IQR) gestational age at delivery of 34 weeks 1 day (31 weeks 5 days to 34 weeks 6 days). All participants delivered before 37 weeks’ gestation. No unexpected serious maternal adverse events occurred, and the most common maternal complications were preterm prelabor rupture of membranes in 19 participants (56%) and chorioamniotic separation in 10 (29%). The primary outcome occurred in 19 (65.5%) of 29 live-born neonates (95% CI, 45.7%-82.1%). Factors associated with survival to the primary outcome included receiving more amnioinfusions (median [IQR], 14 [9-18] in survivors vs 7 [4-11] in nonsurvivors; P = .01), longer time interval from first amnioinfusion to preterm prelabor rupture of membranes (63.5 [60.5-74.5] days in survivors vs 29.0 [22.0-56.0] days in nonsurvivors; P = .01), gestational age greater than 32 weeks (79% of survivors vs 38% of nonsurvivors; P = .03), and higher birth weight (2029 [1770-2250] g in survivors vs 1635 [1185-1915] g in nonsurvivors; P = .01). Fourteen live-born infants (48%) survived to hospital discharge at a median (IQR) age of 4.7 (3.4-5.7) months. Of the 11 infants surviving to date, 7 (64%) have undergone kidney transplant between ages 2 years to 5 years.
Conclusions and relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia in neonates with anhydramnios due to fetal kidney failure. Significant neonatal morbidity and mortality independent of early lung function was noted. Factors associated with survival were consistent with the Renal Anhydramnios Fetal Therapy trial’s bilateral renal agenesis cohort, suggesting common mechanistic pathways for mitigating pulmonary hypoplasia.
Category
Class III. Pulmonary Hypertension Associated with Lung Hypoplasia
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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