Shahid Nadeem1, Shireen Hashmat2, Marissa J Defreitas3, Katherine D Westreich4, Ibrahim F Shatat5, David T Selewski6, Ali M Onder7, Myra Chiang8, Donald J Weaver9, Julia Steinke10, John Barcia11, Joel Hernandez12, Guillermo Hidalgo13, Susan E Ingraham14, Carolyn L Abitbol3, Cynthia Pan2, Larry A Greenbaum15. 1. Louisiana State University Health Sciences Center, Shreveport, LA. Electronic address: snadee@lsuhsc.edu. 2. Medical College of Wisconsin, Milwaukee, WI. 3. University of Miami/Holtz Children's Hospital, Miami, FL. 4. University of North Carolina, Chapel Hill, NC. 5. Sidra Medical and Research Center, Doha, Qatar. 6. University of Michigan, Ann Arbor, MI. 7. West Virginia University, Morgantown, WV. 8. West Virginia University, Charleston, WV. 9. Levine Children's Hospital, Charlotte, NC. 10. Helen DeVos Children's Hospital, Grand Rapids, MI. 11. University of Virginia, Charlottesville, VA. 12. Seattle Children's Hospital, Seattle, WA. 13. East Carolina University, Greenville, NC. 14. Nationwide Children's Hospital, Columbus, OH. 15. Emory University, Atlanta, GA; Children's Healthcare of Atlanta, Atlanta, GA.
Abstract
OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.
OBJECTIVES: Fetuses continue to be exposed to renin angiotensin system (RAS) blockers despite their known teratogenicity and a black box warning. We hypothesized that fetopathy from in utero exposure to RAS blockers has a broader spectrum of clinical manifestations than described previously and that there are a variety of clinical scenarios leading to such exposures. STUDY DESIGN: This was a retrospective study performed through the Midwest Pediatric Nephrology Consortium. Cases of RAS blocker fetopathy were identified, with determination of renal and extrarenal manifestations, timing of exposure, and the explanation for the fetal exposure. RESULTS: Twenty-four cases were identified. RAS blocker exposure after the first trimester was associated with more severe renal manifestations. Chronic dialysis or kidney transplantation was required in 8 of 17 (47%) patients with RAS blocker exposure after the first trimester and 0 of 7 patients with exposure restricted to the first trimester (P = .05). Extrarenal manifestations, some not previously noted in the literature, included central nervous system anomalies (cystic encephalomalacia, cortical blindness, sensorineural hearing loss, arachnoid cysts) and pulmonary complications (pneumothorax, pneumomediastinum). RAS blocker exposure usually was secondary to absent or poor prenatal care or undiagnosed pregnancy. CONCLUSION: RAS blocker fetopathy continues to be a cause of considerable morbidity, with more severe renal manifestations associated with exposure after the first trimester. A variety of significant extrarenal manifestations occur in these patients. Clinicians should emphasize the risk of fetopathy when prescribing RAS blockers to women of childbearing age.
Authors: Frouke N Boonstra; Daniëlle G M Bosch; Christiaan J A Geldof; Catharina Stellingwerf; Giorgio Porro Journal: Front Hum Neurosci Date: 2022-06-30 Impact factor: 3.473