there is an increase in the use of angiotensin ii type 1 receptor antagonists ( at ii antagonists ) and angiotensin - converting enzyme inhibitors ( ace - inhibitors ) as prophylactic treatment of migraines , in addition to their use as antihypertensives .
these drugs pass the placenta and have highly adverse effects on the renal organogenesis , leading to maldevelopment firstly of the renal system and secondarily of the lungs [ 1 , 2 ] .
the fetus is autopsied without conclusive diagnosis . in the woman s next pregnancy , only 6  weeks later
one week later , the midwife finds a declining symphysis to fundus increment , and the woman is therefore immediately referred to the hospital .
, she had three to four attacks every week of unilateral , throbbing pain associated with nausea , vomiting and photophobia , lasting 648  h , preceded by transient scintillating scotomas . during pregnancy ,
, she has been taking candesartan ( 16  mg / day ) , pramipexole ( 0.18  mg 3 ) and amitriptyline ( 25  mg / day ) as prophylaxis against migraines , in addition to zolmitriptan and metoclopramide during attacks .
candesartan treatment was initiated more than a year before her first pregnancy by an experienced neurologist who was also consulted during pregnancy .
the medication was known to her general practitioner and the doctors who conducted the ultrasound examinations .
the hospital obstetricians documented the medication in the admission notes in both pregnancies . nonetheless , the fetus is 33  weeks before doctors become aware that the medication is fetotoxic .
when the baby is born , he has renal tubular dysgenesis , hypoplasia of the skull and the lungs , and hyaline membranes of the lungs .
medline and the norwegian database of adverse effects   were searched for descriptions of fetal injuries related to at ii antagonists ace - inhibitors .
information about the extent of use of these drugs in norway was obtained from the national prescription database .
angiotensin ii receptor antagonists and ace - inhibitors reduce blood pressure by blocking the renin - angiotensin system .
they also have a positive , prophylactic effect against migraines , although the mechanisms are poorly understood .
the colocalization of at1 , glutamate and gaba receptors on medullary rostral ventromedial neurons suggests a nociceptive modulatory .
unfortunately , these drugs cross the placenta and affect the circulation of the fetal kidneys , and , more importantly , reduce stimulation of at ii receptors .
this has a highly adverse effect on the renal organogenesis in the second and third trimesters .
the kidneys develop abnormally and are unable to produce urine ; there is oligohydramnion and thereby , inter alia , maldevelopment of the lungs [ 1 , 2 ] .
the summary of product characteristics in the technical brochures clearly states that these drugs are fetotoxic and should not be used during pregnancy .
more than 20 cases of fetal injury / maldevelopment after exposure to at ii antagonists and ace - inhibitors have been reported in the literature [ 1 , 2 ] .
1.2% of women aged 3039  years were dispensed drugs in 2007 that affect the renin - angiotensin system , an increase compared to 2004 .
more than 50% of childbearing women in norway are more than 30  years old .
the mean age at delivery is increasing and will thus cause the number of pregnant women with hypertension requiring medical treatment to increase . in addition , there is reason to believe that there is an increase in the use of these drugs against migraines .
they are well tolerated , and several studies have demonstrated their positive prophylactic effects [ 711 ] . in american and european guidelines , candesartan is listed among second- and third - line agents , respectively , for migraine prophylaxis [ 1214 ] . in australia
it is not yet listed as an appropriate agent , but is widely used by the neurologists .
this also appears to be the case in norway , although it is difficult to document , as these are not approved drugs against migraines in this country .
a variety of drugs from diverse pharmacological classes are in use for migraine prevention . at ii antagonists and ace - inhibitors are traditional antihypertensives that have proved to be effective also in migraine prophylaxis .
their fetotoxic effects have been demonstrated in humans [ 1 , 2 ] and well documented in animal research . when administered to rats , mice or piglets during renal development
these drugs induce severe renal histological abnormalities , including papillary atrophy , tubulointerstitial fibrosis and tubular atrophy and dilatation [ 16 , 17 ] . nonetheless , there is reason to believe that an increasing number of women of reproductive age will use these drugs .
they should be advised of the possible hazards , and treatment should be stopped as soon as pregnancy is planned or detected .
 a pregnant young woman with a severe migraine is prescribed candesartan , an angiotensin ii type 1 receptor antagonist ( at ii antagonists ) . 
 this has a positive effect  except for severe maldevelopment of her fetus . 
 there is an increase in the use of the fetotoxic drugs , at ii antagonists and angiotensin - converting enzyme inhibitors , as prophylactic treatment of migraines , in addition to their use as hypertensives . 