Prenatal hypocalvaria after prolonged intrauterine exposure to angiotensin II receptor antagonists

Abstract

We report a case of prenatal exposure to angiotensin II receptor antagonists (ARA II) from the beginning of pregnancy in a patient with a hypokinetic dilated cardiomyopathy. This case report emphasizes the fetal renal impact of prolonged intrauterine exposure to renin-angiotensin system (RAS) blockers, and highlights that this exposure can cause severe prenatal hypocalvaria. This delayed ossification can be reversible after birth, but the presence of anhydramnios indicates an early and irreversible block of RAS blockers in the fetus that is responsible for fetal kidney development abnormalities. This association carries a high risk of neonatal death. Prolonged exposure to ARA II or other RAS blockers remains prohibited throughout pregnancy.

Oligohydramnios or Anhydramnios and Ultrasonically Normal Renal Echotexture Secondary to Autosomal Recessive Renal Tubular Dysgenesis: An Important Consideration in the Prenatal Setting

“…Ultrasound demonstrated the absence of macroscopic kidney malformations; however, the urinary bladder was not identified secondary to reduced fetal urine production. There are similar reported cases in the literature [6].…”

“…In most cases, the condition is lethal in the neonatal period due to anuria, respiratory failure from pulmonary hypoplasia, and severe, treatment-refractory hypotension [2]. Additional features are poor skull ossification from an inactive RAS which leads to hypotension, chronic hypoxia, and underdevelopment of the membranous skull bones [5,6].…”

“…The novel feature of this case study is the confirmation of a genetic diagnosis of ARRTD prenatally. A few recent studies have initially investigated oligohydramnios using noninvasive prenatal testing [8] or placental biopsy [6] which showed no chromosomal abnormalities. Further molecular testing and genetic diagnosis of ARRTD were not performed in these cases until the fetus had been born (and subsequently passed away) or terminated.…”

Adverse pregnancy outcomes associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers: A systematic review and meta‐analysis

“…Assumed the observed adverse pregnancy outcomes ascribed mainly to the drugs, the increased teratogenic risk could be conceivably attributed to inhibition of RAAS, a system that plays a key role in the embryogenic and fetal development of several organs/systems 9,58‐60 . Not only does fetal RAAS blockade syndrome occur following ACEI/ARB exposure during the second and third trimesters of pregnancy it also may occur in those who are exposed to ACEIs/ARBs at the beginning of pregnancy 15,61 . Although there are unknown biologic mechanisms underlying adverse birth outcomes, inhibition of angiogenesis has been postulated to be a possible mechanism for the CVS malformations 62 .…”

“…In the 2013 Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy, it has been recommended not to use ACEIs/ARBs in women of reproductive age if there is no compelling reason 12 . Despite such a feature in the labeling of the potentially teratogenic medications, several cases of fetal exposure to ACEIs/ARBs have been reported thereafter 13‐15 . ACEI/ARB exposure during pregnancy is still highly prevalent in many settings 16,17 …”