Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial

Authors

Jena L Miller
Ahmet A Baschat
Mara Rosner
Yair J Blumenfeld
Julie S Moldenhauer
Anthony Johnson
Mauro H Schenone
Michael V Zaretsky
Ramen H Chmait
Juan M Gonzalez
Russell S Miller
Anita J Moon-Grady
Ellen Bendel-Stenzel
Amaris M Keiser
Radhika Avadhani
Angie C Jelin
Jonathan M Davis
Daniel S Warren
Daniel F Hanley
Joslynn A Watkins
Joshua Samuels
Jeremy Sugarman
Meredith A Atkinson

Publication Date

12-5-2023

Journal

JAMA

Abstract

IMPORTANCE: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival.

OBJECTIVE: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia.

DESIGN, SETTING, AND PARTICIPANTS: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies.

EXPOSURE: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age.

MAIN OUTCOMES AND MEASURES: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement.

RESULTS: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks).

CONCLUSIONS AND RELEVANCE: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden.

Keywords

Female, Humans, Infant, Infant, Newborn, Pregnancy, Fetal Therapies, Gestational Age, Kidney, Kidney Diseases, Prospective Studies, Infusions, Parenteral, Oligohydramnios, Fetal Diseases, Lung Diseases, Isotonic Solutions, Ultrasonography, Interventional, Pregnancy Outcome, Treatment Outcome, Premature Birth

Comments

ClinicalTrials.gov Identifier: NCT03101891

Supplementary Materials

PMID: 38051327