Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study

Li, De-Kun; Yang, Chunmei; Andrade, Susan E.; Tavares, Venessa; Ferber, Jeannette

doi:10.1136/bmj.d5931

Cited by 182 publications

(157 citation statements)

References 10 publications

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“…The study showed that hypertension itself appears to be a modest risk for birth defects, particularly cardiac. 4 Similar findings were reported in a smaller Swedish cohort study 5 and a large casecontrol US study. 6 Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study Li et al BMJ 2011;343:d5931 Researchers examined 465,754 mother -infant pairs for the reported link between the use of ACE inhibitors in the first trimester and birth defects.…”

supporting

confidence: 76%

Fetal risk from angiotensin converting enzyme inhibitors in the first trimester

Hotham

2012

Obstet Med

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In 1980, published animal data in The Lancet flagged concerns with the angiotensin converting enzyme (ACE) inhibitor captopril. 1 Publications on the safety of ACE inhibitors followed in the 1980s. By 1993, ACE inhibitor fetopathy had been described in the offspring of patients who took these drugs in the second and third trimesters. The adverse outcomes were deliberately called fetopathy rather than teratogenicity at that time. 2 A 2006 report raised further concerns by demonstrating an association of ACE inhibitors used in the first trimester of pregnancy with an increased rate of birth defects, in particular cardiac malformations and neural tube defects. Other antihypertensive drugs were not associated with increased risks in birth defects. 3 However, in 2011 Li et al., in a retrospective cohort study with a much larger population base and a more ethnically diverse population, did not confirm the reported findings. The study showed that hypertension itself appears to be a modest risk for birth defects, particularly cardiac. 4 Similar findings were reported in a smaller Swedish cohort study 5 and a large casecontrol US study. 6

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supporting

confidence: 76%

Fetal risk from angiotensin converting enzyme inhibitors in the first trimester

Hotham

2012

Obstet Med

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“…In addition, they recommend that for women who have a history of chronic hypertension, the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers is contraindicated for those desiring pregnancy (http://www.acog.org/ResourcesAnd-Publications/Task-Force-and-Work-Group-Reports/ Hypertension-in-Pregnancy). We agree with preconception counseling in high-risk individuals; however, we do not recommend against the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in women with comorbidities, such as diabetes, proteinuria, or CKD, because of the weak evidence of congenital malformations in the first trimester (95,96). We do recommend that these agents be discontinued after pregnancy has been confirmed.…”

Section: Preconception Counseling Prevention Treatment and Postparmentioning

confidence: 89%

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

Phipps

Prasanna

Brima

et al. 2016

CJASN

496

328

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Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a selflimited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after.

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“…Animal studies have not suggested that malformations are likely to result from such treatment, [19] and no mechanism by which ACEIs might interfere with embryogenesis is known [20]. A study by Cooper et al in 2006 reported fetopathy among women dispensed ACEIs during only the first trimester of pregnancy (N=209 children) [21], whereas a much larger study with a more ethnically diverse population did not confirm this [22]. The increased risk of malformations may be more related to the hypertension itself rather than a direct effect of ACEIs [23].…”

Section: Introductionmentioning

confidence: 79%

The Use of Angiotensin Converting Enzyme Inhibitors during the First Trimester of Pregnancy

Colvin¹,

Walters²,

Gill³

et al. 2016

J Pharmacovigilance

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Background: The direct effects of angiotensin converting enzyme inhibitor (ACEI) medications on the fetus are difficult to determine since these medicines are usually administered to women presenting with high-risk pregnancies. The aim of this study was to provide an overview of the dispensing patterns, demographic characteristics and pregnancy outcomes of women dispensed an ACEI during pregnancy. Methods:Exposed pregnancies were all births in Western Australia, 2002Australia, -2005 where the mother was dispensed an ACEI under the Australian Pharmaceutical Benefits Scheme, compared with all other births during the same period.Result: From 2002 to 2005, there were 96,698 births in Western Australia. At least one form of ACEI was dispensed to 95 pregnant women (0.1%) and a further 677 pregnant women (0.7%) were dispensed an antihypertensive medication that was not an ACEI. Women dispensed an ACEI in the first trimester were more likely to be obese (aOR 33.4; 95% CI: 19.5-57.2), to have gestational diabetes (aOR 2.6; 1.3-5.4), to have a preterm delivery (aOR 2.8; 1.4-5.6), and to have smoked during their pregnancy (aOR 1.9; 1.2-3.0). The children of women dispensed an ACEI were more likely to have a major birth defect (aOR 2.6; 1.3-5.2). The risk of a major uro-genital birth defect (aOR 4.8; 2.0-11.7) was increased. Conclusion:Although ACEIs are contraindicated, pregnant women continue to be dispensed these medications. This study provides a profile of these women and their pregnancy outcomes. A clear change in the pattern of dispensing ACEIs later in pregnancy was apparent for these women. A greater number of women were dispensed ACEIs during trimester 1, followed by a marked reduction in dispenses in trimester 2 and trimester 3. Although the number of children affected is small, our data suggests that an increased risk of uro-genital defects may arise with maternal ACEI use in the first trimester.

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Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study

Cited by 182 publications

References 10 publications

Fetal risk from angiotensin converting enzyme inhibitors in the first trimester

Fetal risk from angiotensin converting enzyme inhibitors in the first trimester

Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

The Use of Angiotensin Converting Enzyme Inhibitors during the First Trimester of Pregnancy

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