Maternal olmesartan exposure causing neonatal failure

Abstract

Although angiotensin II receptor blockers (ARBs) are contraindicated during pregnancy, new cases are currently being reported.A 32-week preterm neonate was admitted after C-section due to maternal oligohydramnios. He presented with Potter phenotype, pulmonary hypoplasia with pneumothorax, systemic hypotension and anuria. He required chest drain insertion and continuous positive airway pressure (CPAP), volume expansion plus inotropic support with persistent renal failure. Mother confirmed olmesartan intake during entire pregnancy. Peritoneal dialysis was started with improvement in renal markers and progressive recovery of renal function. He has been followed up until the age of 2 years, observing improved renal function with a glomerular filtration rate (GFR) of 58 mL/min/1.72 m2.Both angiogenesis-converting enzyme inhibitor and ARBs affect nephrogenesis; ARBs being more harmful due to its higher activity. Although some patients may recover normal renal function, its teratogen effect may have fatal consequences. Thus, it is important to emphasise its harmful effects in neonates to avoid new cases.

Lesión renal neonatal secundaria a terapia antihipertensiva materna: reporte de caso

“…El sistema renina angiotensina (SRA) es importante para el desarrollo renal fetal, para el mantenimiento de la filtración glomerular y la presión sanguínea. 7 Durante la gestación, la progesterona ejerce un efecto de reducción del tono vascular y la vasodilatación, estimulando el sistema renina angiotensina aldosterona (SRAA). La renina del aparato yuxtaglomerular actúa sobre el angiotensinógeno intrarrenal, generando angiotensina I y II dando lugar a vasoconstricción arterial y reabsorción de sodio en túbulo renal.…”

“…4 Los receptores tipo 1 localizados en los glomérulos, túbulos y vasculatura renal contribuyen al crecimiento de las nefronas durante el segundo y tercer trimestre; y, el tipo 2 que tienen un papel más determinante en las primeras fases de desarrollo renal en áreas de diferenciación mesenquimática, inhibiendo su crecimiento por mediación de la apoptosis. 7 Además, existe un SRA en la unidad fetoplacentaria que regula la modelación de las arterias espirales y el flujo del espacio intervelloso mediada por la síntesis de prostaglandinas vasodilatadoras por el angiotensinógeno. 4 La nefrogénesis finaliza entre las 34 a 36 SDG, las primeras nefronas aparecen en la novena SDG; pero, la producción de orina se da entre las 10-12 SDG.…”

In Utero Exposure to Antihypertensive Medication during the First Trimester: Is the Risk Worth Taking?

“…Concerning the ARBs, recent studies have confirmed that there is a higher rate of birth defects in cases with ARBs exposure lasting longer than 6 gestational weeks, and this may reveal a teratogenic vulnerability in the second half of the first trimester (26,32). Moreover, ARBs are more dangerous than ACEIs with increasing risk for renal impairment, due to their higher blocking effect and longer half-live (4,33).…”

Quantifying Proximal Collecting Tubule Deficiency in Angiotensin-Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Fetopathy

“…[10][11][12][13] Such association did not change after taking potential confounders into account, including treatment duration, concomitant drug use, concurrent disease and maternal age in a large published series of 110 infants. 14 Exposure to ARB beyond the first trimester of pregnancy appears to be associated with a higher risk for adverse fetal outcomes, 15 with similar phenotypic features as ACEi exposure [16][17][18][19][20] and possible inferior vena cava thrombosis. 21 ARB exposure may have a worse outcome compared with ACEi.…”