Abstracts
Introduction:
The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce.
Case report:
A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions.
Discussion:
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated.
Conclusion:
Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.
angiotensin receptor antagonists; hypertension; pregnancy complications; toxicity
Introdução:
Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos.
Relato do caso:
Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado.
Discussão:
Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado.
Conclusão:
A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão em idade reprodutiva e que podem se tornar gestantes em uso rotineiro destas medicações.
antagonistas de receptores de angiotensina; complicações na gravidez; hipertensão; toxicidade
Introduction
Hypertensive disorders represent a leading cause of maternal and perinatal mortality and
morbidity worldwide.11 Lewis G, ed. Confidential Enquiry into Maternal and Child Health
(CEMACH). Saving Mother's Lives: Reviewing Maternal Deaths to Make Motherhood Safer -
2003-2005. The Seventh Report on Confidential Enquiries into Maternal Deaths in the
United Kingdom. London: CEMACH; 2007.,22 Oliveira LG, Karumachi A, Sass N. Pré-eclâmpsia: estresse oxidativo,
inflamação e disfunção endotelial. Rev Bras Ginecol Obstet 2010;32:609-16. DOI:
http://dx.doi.org/10.1590/S0100-72032010001200008
http://dx.doi.org/10.1590/S0100-72032010...
Furthermore, most of the morbidity associated with
hypertensive disorders is concentrated among pregnancies complicated by pre-eclampsia
and eclampsia, which are the first and second leading causes of maternal death.33 Health Canada. Special Report on Maternal Mortality and Severe Morbidity
in Canada - Enhanced Surveillance: the Path to Prevention. Ottawa: Minister of Public
Works and Government Services Canada; 2004. Moreover, for every woman who dies, approximately
20 others suffer severe morbidity.44 Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of
causes of maternal death: a systematic review. Lancet 2006;367:1066-74. PMID:
16581405 DOI: http://dx.doi.org/10.1016/S0140-6736(06)68397-9
http://dx.doi.org/10.1016/S0140-6736(06)...
Currently, it is widely accepted that sustained, severe hypertension (e.g., blood
pressure > 160/110 mmHg) during pregnancy should be treated, since it is considered a
risk factor for maternal end-organ complications (such, as stroke), independent of
preeclampsia.55 Report of the National High Blood Pressure Education Program Working
Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol
2000;183:S1-S22.
6 Pavan MV, Saura GE, Korkes HA, Nascimento KM, Madeira Neto ND, Dávila R,
et al. Similarity between blood pressure values assessed by auscultatory method with
mercury sphygmomanometer and automated oscillometric digital device. J Bras Nefrol
2012;34:43-9. DOI: http://dx.doi.org/10.1590/S0101-28002012000100007
http://dx.doi.org/10.1590/S0101-28002012...
-77 Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw
S; CHIPS Study Group. How to manage hypertension in pregnancy effectively. Br J Clin
Pharmacol 2011;72:394-401. DOI:
http://dx.doi.org/10.1111/j.1365-2125.2011.04002.x
http://dx.doi.org/10.1111/j.1365-2125.20...
However, insufficient evidence is available to
guide the optimal use of antihypertensives for non-severe hypertension (e.g., blood
pressure 140-159 mmHg/90-109 mmHg) during pregnancy.77 Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw
S; CHIPS Study Group. How to manage hypertension in pregnancy effectively. Br J Clin
Pharmacol 2011;72:394-401. DOI:
http://dx.doi.org/10.1111/j.1365-2125.2011.04002.x
http://dx.doi.org/10.1111/j.1365-2125.20...
,88 Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et
al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J
Obstet Gynecol 2013;208:301.e1-6. DOI:
http://dx.doi.org/10.1016/j.ajog.2012.11.011
http://dx.doi.org/10.1016/j.ajog.2012.11...
Therefore, treatment of
non-severe hypertension remains controversial due to the lack of clarity regarding
benefits and risks for mother and child, as well as concerns about fetal programming
effects.77 Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw
S; CHIPS Study Group. How to manage hypertension in pregnancy effectively. Br J Clin
Pharmacol 2011;72:394-401. DOI:
http://dx.doi.org/10.1111/j.1365-2125.2011.04002.x
http://dx.doi.org/10.1111/j.1365-2125.20...
,88 Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et
al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J
Obstet Gynecol 2013;208:301.e1-6. DOI:
http://dx.doi.org/10.1016/j.ajog.2012.11.011
http://dx.doi.org/10.1016/j.ajog.2012.11...
Case report
A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension over the past five years, and was currently being treated with Losartan (50 mg per day) on a regular basis to maintain adequate blood pressure levels. After admission to the prenatal services of our hospital, routine tests were conducted, and her antihypertensive medication was changed to methyldopa.
When ultrasonography (US) was performed, a single live fetus was observed in pelvic presentation. It had an estimated weight of 1007 g, had a placenta grade of 0 according to Granum classification, an absence of amniotic fluid was detected, and a gestational age of 26 weeks and 4 days was estimated. Elective hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. Corticotherapy was also administered with 12 mg betametasona given in two cycles.
On the fourth day of hospitalization, routine tests were normal, 24 hours proteinuria assay was negative, and the patient's hypertension was adequately controlled. Another US was performed, resulting in a gestational estimate of 27 weeks and 1 day. Pelvic presentation was still observed and the estimated weight of the fetus was 918 g. In addition, severe oligohydramnios was detected. A Doppler examination further revealed fetal centralization with abnormal ductus venosus. Magnesium sulfate was subsequently administered for neuroprotection of the fetus and a cesarean delivery was scheduled.
The delivery was performed with no intercurrence and the birth of a male newborn was achieved. The newborn weighed 1050 g, had an Apgar score of 1 and 5 at the first and fifth minutes, and he required no neonatal resuscitation or orotracheal intubation in the delivery room. However, after 36 hours, the newborn progressed to cardiac arrest and died.
Pathologic evaluation
At autopsy, the fetus weighed 1050 g and manifested the appropriate dimensions for its gestational age. The skullcap had large fontanels and deficient ossification. A slight reduction in lung volume was observed (right, 6.3 g; left, 5.0 g; normal range, 27.0 ± 7.0 g). The kidneys were also slightly enlarged (combined weight, 20.3 g; normal range, 12.0 ± 4.0 g). Following preservation of the kidneys, a microscopic examination further detected underdevelopment of the tubules and the presence of some dilated lumens (Figure 1) compared with normal (Figure 2). Immunohistochemical detection of epithelial membrane antigen (EMA) (typically performed for distal tubules) was positive (Figure 3). Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions (Figure 4). Brain changes secondary to ischemia, including softening of the semi-oval center focus of perivascular hemorrhage in the head of the caudate nucleus and small hemorrhage in the IV ventricle were observed. Foci of hemorrhage were also observed in the lungs. However, the other organs presented no notable changes.
Staining of paraffin-embedded kidney sections by haematoxylin and eosin showed normal development of glomerular structures with a disarray of cortical zone, decreased numbers of tubules, abundant mesenchimal tissue, abnormal, irregular size and enlarge tubules, and proximal and distal convoluted tubules could not be distinguished. The tubular structures were lined by hypoplatic epithelial cells (cuboidal cells) with prominent lumena. Magnification x100.
Staining of paraffin-embedded kidney sections by haematoxylin and eosin show normal renal development in a liveborn fetus at 39 weeks gestation. Distal tubules well developed and stained acidofilic by eosin. Magnifications: x100.
Positive immunolabeling of distal tubules using monoclonal antibodies raised against anti-epithelial (EMA) showed decreased numbers of these structures and poor differentiation. Magnification: x100.
Immunoperoxidase staining with an anti-CD15 antibody. Decreased numbers of proximal tubules and poor differentiation were observed. Magnifications: x100.
Discussion
The potential risks related to drug exposure during pregnancy represent a vast chapter
in modern obstetrics. For patients with hypertension who qualify for medication, there
are several antihypertensive alternatives available for clinical application, and these
do not appear to have a risk of teratogenicity or fetotoxicity.99 Cooper WO. Clinical implications of increased congenital malformations
after first trimester exposures to angiotensin-converting enzyme inhibitors. J
Cardiovasc Nurs 2008;23:20-4. DOI:
http://dx.doi.org/10.1097/01.JCN.0000305052.73376.de
http://dx.doi.org/10.1097/01.JCN.0000305...
10 Moretti ME, Caprara D, Drehuta I, Yeung E, Cheung S, Federico L, et al.
The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II
Receptor Blockers. Obstet Gynecol Int 2012;2012:658310. PMID: 22203847 DOI:
http://dx.doi.org/10.1155/2012/658310
http://dx.doi.org/10.1155/2012/658310...
-1111 Karthikeyan VJ, Ferner RE, Baghdadi S, Lane DA, Lip GY, Beevers DG. Are
angiotensin-converting enzyme inhibitors and angiotensin receptor blockers safe in
pregnancy: a report of ninety-one pregnancies. J Hypertens 2011;29:396-9. DOI:
http://dx.doi.org/10.1097/HJH.0b013e328341885d
http://dx.doi.org/10.1097/HJH.0b013e3283...
However, data
regarding the safety of antihypertensive drugs during pregnancy are relatively
scarce.99 Cooper WO. Clinical implications of increased congenital malformations
after first trimester exposures to angiotensin-converting enzyme inhibitors. J
Cardiovasc Nurs 2008;23:20-4. DOI:
http://dx.doi.org/10.1097/01.JCN.0000305052.73376.de
http://dx.doi.org/10.1097/01.JCN.0000305...
,1212 Briggs GG, Freeman RK, Yaffe, SJ. Drugs in pregnancy and lactation: a
Reference guide to fetal and neonatal risk. 9th ed. Baltimore: Lippincott, Williams
& Wilkins; 2011. There is evidence from animal studies that administration of
angiotensin-converting enzyme inhibitors (ACEIs) during pregnancy is associated with
fetal toxicity and an increased rate of stillbirths.1313 Broughton Pipkin F, Turner SR, Symonds EM. Possible risk with captopril
in pregnancy: some animal data. Lancet 1980;1:1256. DOI:
http://dx.doi.org/10.1016/S0140-6736(80)91723-7
http://dx.doi.org/10.1016/S0140-6736(80)...
Treatment with angiotensin receptor antagonists (ARAs) has similar risks,
and is also associated with oligohydramnios, fetal growth retardation, pulmonary
hypoplasia, neonatal hypotension, renal failure with oliguria/anuria, renal tubular
abnormalities, and calvarial hypoplasia.1414 Quan A. Fetopathy associated with exposure to angiotensin converting
enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev 2006;82:23-8.
PMID: 16427219 DOI:
http://dx.doi.org/10.1016/j.earlhumdev.2005.11.001
http://dx.doi.org/10.1016/j.earlhumdev.2...
15 Schaefer C. Angiotensin II-receptor-antagonists: further evidence of
fetotoxicity but not teratogenicity. Birth Defects Res A Clin Mol Teratol
2003;67:591-4. DOI: http://dx.doi.org/10.1002/bdra.10081
http://dx.doi.org/10.1002/bdra.10081...
16 Velázquez-Armenta EY, Han JY, Choi JS, Yang KM, Nava-Ocampo AA.
Angiotensin II receptor blockers in pregnancy: a case report and systematic review of
the literature. Hypertens Pregnancy 2007;26:51-66. DOI:
http://dx.doi.org/10.1080/10641950601147937
http://dx.doi.org/10.1080/10641950601147...
-1717 Diav-Citrin O, Shechtman S, Halberstadt Y, Finkel-Pekarsky V, Wajnberg
R, Arnon J, et al. Pregnancy outcome after in utero exposure to angiotensin
converting enzyme inhibitors or angiotensin receptor blockers. Reprod Toxicol
2011;31:540-5. PMID: 21338666 DOI:
http://dx.doi.org/10.1016/j.reprotox.2011.02.008
http://dx.doi.org/10.1016/j.reprotox.201...
The most widely used ARAs include losartan, candesartan, valsartan, and tasosartan,1414 Quan A. Fetopathy associated with exposure to angiotensin converting
enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev 2006;82:23-8.
PMID: 16427219 DOI:
http://dx.doi.org/10.1016/j.earlhumdev.2005.11.001
http://dx.doi.org/10.1016/j.earlhumdev.2...
and these medications modulate the
renin-angiotensin-aldosterone system by selectively blocking type 1 angiotensin II
receptors.1818 Walfisch A, Al-maawali A, Moretti ME, Nickel C, Koren G. Teratogenicity
of angiotensin converting enzyme inhibitors or receptor blockers. J Obstet Gynaecol
2011;31:465-72. PMID: 21823839 DOI:
http://dx.doi.org/10.3109/01443615.2011.579197
http://dx.doi.org/10.3109/01443615.2011....
ACEIs and ARAs are among the most widely prescribed drugs for hypertension. While their
fetal toxicity in the second or third trimesters has been documented,1515 Schaefer C. Angiotensin II-receptor-antagonists: further evidence of
fetotoxicity but not teratogenicity. Birth Defects Res A Clin Mol Teratol
2003;67:591-4. DOI: http://dx.doi.org/10.1002/bdra.10081
http://dx.doi.org/10.1002/bdra.10081...
,1919 Alwan S, Polifka JE, Friedman JM. Angiotensin II receptor antagonist
treatment during pregnancy. Birth Defects Res A Clin Mol Teratol 2005;73:123-30.
PMID: 15669052 DOI: http://dx.doi.org/10.1002/bdra.20102
http://dx.doi.org/10.1002/bdra.20102...
their teratogenic effect during the first trimester has only recently been
demonstrated.2020 Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med
2006;354:2498-500. PMID: 16760451 DOI:
http://dx.doi.org/10.1056/NEJMe068089
http://dx.doi.org/10.1056/NEJMe068089...
,2121 Li DK, Yang C, Andrade S, Tavares C, Ferber JR. Maternal exposure to
angiotensin converting enzyme inhibitors in the first trimester and risk of
malformations in offspring: a retrospective cohort study. BMJ 2011;343:d5931. DOI:
http://dx.doi.org/10.1136/bmj.d5931
http://dx.doi.org/10.1136/bmj.d5931...
In a recent meta-analysis of five observational cohorts, including 786 exposed infants
and over one million controls, first trimester exposure to ACEIs or ARAs did not lead to
a higher risk of major congenital malformations compared to other antihypertensive
drugs.1818 Walfisch A, Al-maawali A, Moretti ME, Nickel C, Koren G. Teratogenicity
of angiotensin converting enzyme inhibitors or receptor blockers. J Obstet Gynaecol
2011;31:465-72. PMID: 21823839 DOI:
http://dx.doi.org/10.3109/01443615.2011.579197
http://dx.doi.org/10.3109/01443615.2011....
Inadvertent exposure to these drugs
in the first trimester of pregnancy has also not been found to present significant risks
for malformations in live births, however, higher rates of spontaneous abortion have
been reported for patients prescribed.1010 Moretti ME, Caprara D, Drehuta I, Yeung E, Cheung S, Federico L, et al.
The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II
Receptor Blockers. Obstet Gynecol Int 2012;2012:658310. PMID: 22203847 DOI:
http://dx.doi.org/10.1155/2012/658310
http://dx.doi.org/10.1155/2012/658310...
In
addition, an increased risk for cardiovascular and central nervous system malformations
in infants whose mothers were prescribed an ACEI during their first trimester was
recently reported.2222 Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS,
et al. Major congenital malformations after first-trimester exposure to
ACE-inhibitors. N Engl J Med 2006;354:2443-51. PMID: 16760444 DOI:
http://dx.doi.org/10.1056/NEJMoa055202
http://dx.doi.org/10.1056/NEJMoa055202...
Given the conflicting data regarding the adverse effects of ACEIs and ARAs during pregnancy, the authors believe that as a preventive policy, physicians should not routinely prescribe these drugs for pregnant women, or for women who are considering becoming pregnant. Information regarding possible adverse events associated with these drugs should also be provided to patients, with informed consent required for women of childbearing age who elect to receive such drugs.
Conclusion
It is known that drugs with possible harmful fetal effects are included in the therapeutic armamentarium for many diseases, and that it is possible women will become pregnant when using these medications. Thus, constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant.
References
-
1Lewis G, ed. Confidential Enquiry into Maternal and Child Health (CEMACH). Saving Mother's Lives: Reviewing Maternal Deaths to Make Motherhood Safer - 2003-2005. The Seventh Report on Confidential Enquiries into Maternal Deaths in the United Kingdom. London: CEMACH; 2007.
-
2Oliveira LG, Karumachi A, Sass N. Pré-eclâmpsia: estresse oxidativo, inflamação e disfunção endotelial. Rev Bras Ginecol Obstet 2010;32:609-16. DOI: http://dx.doi.org/10.1590/S0100-72032010001200008
» http://dx.doi.org/10.1590/S0100-72032010001200008 -
3Health Canada. Special Report on Maternal Mortality and Severe Morbidity in Canada - Enhanced Surveillance: the Path to Prevention. Ottawa: Minister of Public Works and Government Services Canada; 2004.
-
4Khan KS, Wojdyla D, Say L, Gulmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066-74. PMID: 16581405 DOI: http://dx.doi.org/10.1016/S0140-6736(06)68397-9
» http://dx.doi.org/10.1016/S0140-6736(06)68397-9 -
5Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1-S22.
-
6Pavan MV, Saura GE, Korkes HA, Nascimento KM, Madeira Neto ND, Dávila R, et al. Similarity between blood pressure values assessed by auscultatory method with mercury sphygmomanometer and automated oscillometric digital device. J Bras Nefrol 2012;34:43-9. DOI: http://dx.doi.org/10.1590/S0101-28002012000100007
» http://dx.doi.org/10.1590/S0101-28002012000100007 -
7Magee LA, Abalos E, von Dadelszen P, Sibai B, Easterling T, Walkinshaw S; CHIPS Study Group. How to manage hypertension in pregnancy effectively. Br J Clin Pharmacol 2011;72:394-401. DOI: http://dx.doi.org/10.1111/j.1365-2125.2011.04002.x
» http://dx.doi.org/10.1111/j.1365-2125.2011.04002.x -
8Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J Obstet Gynecol 2013;208:301.e1-6. DOI: http://dx.doi.org/10.1016/j.ajog.2012.11.011
» http://dx.doi.org/10.1016/j.ajog.2012.11.011 -
9Cooper WO. Clinical implications of increased congenital malformations after first trimester exposures to angiotensin-converting enzyme inhibitors. J Cardiovasc Nurs 2008;23:20-4. DOI: http://dx.doi.org/10.1097/01.JCN.0000305052.73376.de
» http://dx.doi.org/10.1097/01.JCN.0000305052.73376.de -
10Moretti ME, Caprara D, Drehuta I, Yeung E, Cheung S, Federico L, et al. The Fetal Safety of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers. Obstet Gynecol Int 2012;2012:658310. PMID: 22203847 DOI: http://dx.doi.org/10.1155/2012/658310
» http://dx.doi.org/10.1155/2012/658310 -
11Karthikeyan VJ, Ferner RE, Baghdadi S, Lane DA, Lip GY, Beevers DG. Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers safe in pregnancy: a report of ninety-one pregnancies. J Hypertens 2011;29:396-9. DOI: http://dx.doi.org/10.1097/HJH.0b013e328341885d
» http://dx.doi.org/10.1097/HJH.0b013e328341885d -
12Briggs GG, Freeman RK, Yaffe, SJ. Drugs in pregnancy and lactation: a Reference guide to fetal and neonatal risk. 9th ed. Baltimore: Lippincott, Williams & Wilkins; 2011.
-
13Broughton Pipkin F, Turner SR, Symonds EM. Possible risk with captopril in pregnancy: some animal data. Lancet 1980;1:1256. DOI: http://dx.doi.org/10.1016/S0140-6736(80)91723-7
» http://dx.doi.org/10.1016/S0140-6736(80)91723-7 -
14Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev 2006;82:23-8. PMID: 16427219 DOI: http://dx.doi.org/10.1016/j.earlhumdev.2005.11.001
» http://dx.doi.org/10.1016/j.earlhumdev.2005.11.001 -
15Schaefer C. Angiotensin II-receptor-antagonists: further evidence of fetotoxicity but not teratogenicity. Birth Defects Res A Clin Mol Teratol 2003;67:591-4. DOI: http://dx.doi.org/10.1002/bdra.10081
» http://dx.doi.org/10.1002/bdra.10081 -
16Velázquez-Armenta EY, Han JY, Choi JS, Yang KM, Nava-Ocampo AA. Angiotensin II receptor blockers in pregnancy: a case report and systematic review of the literature. Hypertens Pregnancy 2007;26:51-66. DOI: http://dx.doi.org/10.1080/10641950601147937
» http://dx.doi.org/10.1080/10641950601147937 -
17Diav-Citrin O, Shechtman S, Halberstadt Y, Finkel-Pekarsky V, Wajnberg R, Arnon J, et al. Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Reprod Toxicol 2011;31:540-5. PMID: 21338666 DOI: http://dx.doi.org/10.1016/j.reprotox.2011.02.008
» http://dx.doi.org/10.1016/j.reprotox.2011.02.008 -
18Walfisch A, Al-maawali A, Moretti ME, Nickel C, Koren G. Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers. J Obstet Gynaecol 2011;31:465-72. PMID: 21823839 DOI: http://dx.doi.org/10.3109/01443615.2011.579197
» http://dx.doi.org/10.3109/01443615.2011.579197 -
19Alwan S, Polifka JE, Friedman JM. Angiotensin II receptor antagonist treatment during pregnancy. Birth Defects Res A Clin Mol Teratol 2005;73:123-30. PMID: 15669052 DOI: http://dx.doi.org/10.1002/bdra.20102
» http://dx.doi.org/10.1002/bdra.20102 -
20Friedman JM. ACE inhibitors and congenital anomalies. N Engl J Med 2006;354:2498-500. PMID: 16760451 DOI: http://dx.doi.org/10.1056/NEJMe068089
» http://dx.doi.org/10.1056/NEJMe068089 -
21Li DK, Yang C, Andrade S, Tavares C, Ferber JR. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 2011;343:d5931. DOI: http://dx.doi.org/10.1136/bmj.d5931
» http://dx.doi.org/10.1136/bmj.d5931 -
22Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, et al. Major congenital malformations after first-trimester exposure to ACE-inhibitors. N Engl J Med 2006;354:2443-51. PMID: 16760444 DOI: http://dx.doi.org/10.1056/NEJMoa055202
» http://dx.doi.org/10.1056/NEJMoa055202
Publication Dates
-
Publication in this collection
Jul-Sep 2014
History
-
Received
21 Feb 2014 -
Accepted
26 May 2014