ace inhibitors and arbs , the most potent antihypertensive and renoprotective pharmaceutical agents also recognized for their cardioprotective activity , have been widely applied to a number of illnesses .
these agents function by interruption of the production or action of angiotensin ii , which is the main end - product of the renin 
clinical consequences include ( a ) reduction of glomerular capillary pressure , ( b ) reduction of systolic blood pressure and proteinuria and ( c ) an antiproliferative effect , all of which are considered major actions of these drugs .
their side effects , which have been extensively studied in animals and humans , are classified into three categories : ( a ) those related to pharmacologic action , ( b ) those related to chemical structure and ( c ) those involving hypoperfusion of fetal vasculature , including that of renal tissue .
the first category is likely related to women exposed to a pharmaceutical toxic effect during pregnancy and this effect may influence the expression of genes related to the renin 
side effects related to hypoperfusion of fetal vasculature ( or ace inhibitors arbs fetopathy ) include renal insufficiency , tubular dysplasia , fetal anuria with oligohydramnios , hypocalvaria , pulmonary hypoplasia and intrauterine death .
since the discovery of these agents in 1965 , many studies have reported the effects of ace inhibitors on the fetus and maternal exposure , especially during the second and third trimesters of pregnancy [ 47 ] .
subsequently , arbs were manufactured ; these powerful antihypertensive drugs are highly selective and specific to the renin 
angiotensin system and were developed with the aim of having less adverse effects on the fetus .
however , a number of side effects similar to those described in fetuses and newborns of women treated during pregnancy with ace inhibitors have been reported .
the present study describes a pregnant woman who was hypertensive for the last 3 years and treated during the entire pregnancy period with olmesartan medoxomil , the seventh of manufactured arb agents . following severe oligohydramnios , diagnosed at 33 gestational weeks
, she underwent a caesarean section and gave birth to a female baby . in the first 48 postnatal hours
the mother was a 40-year - old primigravida with a 3-year history of essential hypertension .
she was treated with olmesartan medoxomil ( olmetec munich , germany ) , a single daily dose of 20 mg , and her hypertension was well controlled with this regimen .
her conception was assisted by ivf . at 33 weeks of gestation , a severe degree of oligohydramnios was diagnosed by ultrasonographic evaluation .
a premature female baby was delivered , with a weight of 1.980 g , length 45 cm and occipital  frontal circumference 30.5 cm .
shortly after the birth , the newborn presented respiratory distress syndrome , and was intubated and ventilated with oxygen supplementation ; the newborn received two doses of sulfactant .
oligoanuria was also observed on the first and second postnatal days . on the third day post - birth ,
renal ultrasonography revealed two kidneys of normal size with increased echogenicity , while on the fifth postnatal day , the plasma creatinine level was 3.1 mg / dl .
the neonate was transferred from the maternity hospital to the neonatal intensive care unit at the children 's hospital for further assessment and management . on admission , the newborn
suffered from breathing difficulty and acute renal failure and was on ncpap 21% o2 . on several occasions ,
dolichocephaly with cranial and facial asymmetries , light dysplasia of the external ear , equestrian figures of the feet , wide anterior fontanel and dilatation of celebral ventricles were also detected .
all of these facial characteristics were likely closely related to the severe degree of oligohydramnios . on brain ultrasonography ,
ihv of first degree on both sides and increased periventricular echogenicity were recorded , as well as a small asymmetry of lateralis ventricle of brain l > r .
repeated renal ultrasonography confirmed the previously reported findings of increased echogenicity on two otherwise normal kidneys .
muscular tone and neonatal reflexes were normal for the age of gestation , but wide anterior fontanel and sutures were detected .
laboratory findings on admission were as follows : hb 11.5 g / dl , ht 35% , wbc 13.3  10/l ( pmn46% , l32% , m13% ) , plt 223  10 l , glucose 80 mg / dl , urea 201 mg / dl , creatinine 2.8 mg / dl , uric acid 12.9 mg / dl , urine spot for fena 13% , sgot 16 u / l , sgpt 17 u / l , -gt 56 u / l , alp 114 u / l , ca 9.7 mg / dl , p 7.4 mg / dl , mg 2.8 mg / dl , k 3.9 mmol / l , na 134 mmol / l , cl 88
mmol / l , ua 12.6 mg / dl , total bilirubin 3.1 mg / dl , direct 0.93 mg / dl , cpk 64 iu / l , ldh 342 iu / l , total protein 4.4 g / dl , albumin 2.8 g / dl , crp 0.43 mg / l , plasma aldosterone 872 ng / dl ( normal 19141 ng / dl ) and renin 507 pg / ml ( normal 40 220 pg / ml ) . during hospitalization , several challenges
cpap was continued for 3 days post - admission followed by diffuse o2 for the next 24 h. following a conservative approach , meticulous fluid and electrolyte adjustment resulted in a gradual improvement of renal function so that by day 19 after birth , the plasma creatinine level was 0.9% .
plasma creatinine levels during the first 2 weeks of postnatal period and at 1 year of life are displayed in figure 1 .
the acute renal failure event and severe degree of oligohydramnios were both attributed to the mother 's antihypertensive therapy and are related to the temporarily reduced fetal gfr .
one month post - admission , the baby was discharged from the unit in good condition with urea 25 mg / dl , plasma creatinine 0.8 mg / dl and renal trasonographic findings compatible with normal sized kidneys and normal parenchyma echogenicity . at the latest follow - up examination ,
the baby ( 1 year old ) was well developed and normotensive ( bp 105/60 mmhg ) .
renal function tests showed 35 mg / dl and 0.5 mg / dl plasma urea and creatinine levels , respectively .
the renin  angiotensin system is very active during fetal organogenesis and plays an important role , particularly in renal development . as early as 1980
, well - documented animal studies showed that treatment with ace inhibitors during pregnancy causes fetal anomalies or fetal loss due to severe hypoperfusion .
one year later , the first case report on a human fetus exposed to ace inhibitors was published , and many studies have been reported since then . in 1992 ,
the food and drug administration ( fda ) strongly emphasized a warning , especially to the obstetrical community , concerning the use of these agents during pregnancy . in 1995 , it was estimated that 50% of neonates born to mothers exposed to ace inhibitors would be affected by these treatments , while another 25% of the births would be fatal .
arbs were later developed as an alternative treatment , aimed to have less adverse effects on the fetus .
both ace inhibitors and arbs , however , are very powerful antihypertensive agents with a similar clinical outcome , and most of the effects in the maternal kidneys have been determined to be due to the dilatation of the efferent arterioles of the glomerulus .
it results in hypoperfusion and a decrease in the glomerular filtration rate , which likely affects the development of the fetus .
moreover , these pharmaceutics are excreted by the kidneys and can cross human placenta to be excreted into the amniotic fluid and presumably be swallowed by the fetus .
therefore , fetal hypoperfusion and the consequent anomalies involving the kidneys are not only indirectly related to the mother 's hypotensive status , but also directly related to the drugs in the fetal circulation .
additionally , it is possible that exposure to a pharmaceutical toxic agent could also influence the expression of renin  angiotensin system genes .
a number of reports have shown that administration of arbs in early pregnancy , or at least during the first trimester , is related to 6% of the major abnormalities [ 1416 ] . to our knowledge , 11 reports have been published describing side effects in the fetuses of mothers exposed to arbs during their second and third trimesters of pregnancy .
nearly all pregnant women treated by these agents gave birth to babies either suffering from fetal abnormalities or born dead .
it is of interest that valsartan and losartan were used in four and three of the reported cases , respectively , and all cases of losartan treatments died [ 3,4,9,1719 ] . however , another study reported that three normal babies were born to mothers treated by arbs during their first trimester of pregnancy .
the most recently developed arb is olmesartan olmetic , and its use during pregnancy , at a dose of 10 mg / day , has only been reported once . according to the authors of this previous study , following oligohydramnios diagnosis at 29 gestation weeks , olmesartan olmetic regimen was withdrawn and rehydration along with a single dose of furosemide was administered to the pregnant woman .
the result of this early intrauterine intervention was a healthy baby , born without renal or other abnormalities .
it was therefore postulated that fetus renal dysfunction , following olmesartan olmetic maternal exposure , is probably reversible .
our reported findings are , to some extent , consistent with this paper . in our case ,
the affected newborn was also exposed during his entire fetal life to olmesartan medoxomil at a dose of 20 mg / day . despite oligohydramnios diagnosis
apart from various characteristics , mainly craniofacial directly related to oligohydramnios , the neonate suffered from oligoanuric type acute renal failure during the first weeks of life due to olmesartan medoxomil exposure .
renal ultrasonographic findings of increased echogenicity on two otherwise normal kidneys are consistent with acute renal damage .
the baby responded very well to the conservative management , and within first 2 weeks of life , recovery of renal function was observed .
thus , one possibility is that fetal renal toxicity following maternal exposure to olmesartan medoxomil is dose related .
another possible explanation is that the adverse reaction of arbs may be due to genetic polymorphisms in drug - inhibiting enzymes or receptor blockers , which would alter drug concentration , thus affecting drug response . in summary , here we reported a case of a premature female baby born with oligoanuric type of acute renal failure following the mother 's exposure to olmesartan medoxomil .
we observed a gradual recovery of renal function during the first 2 weeks of life , and therefore , considered that renal impairment was transient . at the latest follow - up
1 year later , renal function was normal , arguing against the presence of irreversible renal damage . whether this specific antihypertensive agent , olmesartan medoxomil , administered during pregnancy at the dose of 20 mg daily is generally safe with no side effects for the fetus is not yet clear .
 angiotensin - converting enzyme ( ace ) inhibitors and angiotensin ii ( at ii ) receptor blockers ( arbs ) are widely used antihypertensives with well - recognized renoprotective and cardioprotective effects . 
 although treatment with these agents generally does not result in adverse metabolic consequences , their use during human pregnancy has been associated with negative reactions . here 
 we report a premature baby with a history of oligohydramnios and maternal exposure to the arb olmesartan medoxomil who was transferred to our institution with acute renal failure . 
 conservative treatment with diuretics and meticulous management of fluids and electrolytes resulted in an improvement in renal function in the patient . 
 we conclude that olmesartan medoxomil may cause reversible renal failure in premature neonates . 
Introduction
Case report
Discussion