Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment

Tabacova, Sonia; Little, Ruth E.; Tsong, Yi; Vega, Amarilys; Kimmel, Carole A.

doi:10.1002/pds.796

Cited by 107 publications

(56 citation statements)

References 33 publications

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“…However, this has been questioned by a recent study reporting that the risk of malformations after antihypertensive treatment with a AngII receptor blocker in diabetic women during the first trimester was very low (51). Furthermore, treatment with ACE inhibitors during the last part of pregnancy is associated with abnormal fetal renal development and neonatal renal failure (52). Treatment with ACE inhibitors or AngII antagonists should therefore be stopped before conception (50,52); however, if these drugs are given during organogenesis, the risk of malformations is so low that interruption of the pregnancy in not necessary.…”

Section: Bp Controlmentioning

confidence: 99%

“…Furthermore, treatment with ACE inhibitors during the last part of pregnancy is associated with abnormal fetal renal development and neonatal renal failure (52). Treatment with ACE inhibitors or AngII antagonists should therefore be stopped before conception (50,52); however, if these drugs are given during organogenesis, the risk of malformations is so low that interruption of the pregnancy in not necessary. It is often wise to change to other types of antihypertensive treatment that are regarded safe in pregnancy, such as methyldopa, b-blockers (labetalol), or calcium antagonists.…”

Section: Bp Controlmentioning

confidence: 99%

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Obstetric Nephrology

Mathiesen

Ringholm

Feldt‐Rasmussen

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryThis review highlights factors of importance for the clinical care of pregnant women with pregestational diabetes and microalbuminuria or diabetic nephropathy with particular focus on the role of intensive antihypertensive treatment during pregnancy. Most information in the literature comes from women with type 1 diabetes and diabetic nephropathy, but this is probably also valid for women with type 2 diabetes. Careful counseling of women with diabetic nephropathy before pregnancy with estimation of the risk for the mother and fetus is important. Pregnancy does not result in worsening of kidney function in women with diabetic nephropathy and normal serum creatinine, but pregnancy complications such as pre-eclampsia and preterm delivery are common. Intensive metabolic control before and during pregnancy, low-dose aspirin from 12 gestational weeks onward, and intensive antihypertensive treatment are important. Methyldopa, labetalol, and nifedipine are regarded safe in pregnancy, whereas angiotensin converting enzyme inhibitors, AngII antagonists, or statins should be paused before pregnancy. Case series and pathophysiological studies support the use of a stringent goal for BP and albumin excretion in pregnant women with diabetic nephropathy. Screening for diabetic retinopathy before and during pregnancy is mandatory and laser treatment should be performed if indicated. Pregnancy outcome in women with diabetic nephropathy has improved considerably with a take-home-baby rate of approximately 95%. Further research on the benefits and risks of intensive antihypertensive treatment in this population is needed.

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Section: Bp Controlmentioning

confidence: 99%

Section: Bp Controlmentioning

confidence: 99%

Obstetric Nephrology

Mathiesen

Ringholm

Feldt‐Rasmussen

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…A species comparison of the effects of angiotensin converting enzyme inhibition (Tabacova et al, 2003) is important to understanding why the human fetus suffers adverse consequences from exposure whereas rodent fetuses do not. The greater susceptibility of the human fetus to pharmacological agents such as enalapril and other angiotensin converting enzyme inhibitors is a function of the relative maturity of the kidney and the renin-angiotensin system, which are the specific targets during intrauterine development.…”

Section: Consequences Of Exposuresmentioning

confidence: 99%

“…The susceptibilities identified in Table 4 are covered in In chapter 3, the structural and functional features that potenanimal species. For example, as documented in chapter 3, some (Bailey et al, 2003) Embryonic age Neural tube defects from retinoic acid, arsenic, and valproic acid (Adams, 1993;Bennett & Finnell, 1998) Decreased fertility in female rats exposed to dioxin (TCDD) (Gray & Ostby, 1995) Hydronephrosis with dioxin exposure during embryonic or fetal periods in rats (Couture-Haws et al, 1991;Birnbaum, 1995) Fetus Decreased intelligence, increased behavioural problems with lead (Bellinger et al, 1994;Rice, 1996) Cerebral palsy, mental retardation with high-dose methylmercury (Harada, 1978); subtle neurobehavioural effects with low doses (Grandjean et al, 1997) Exposure to several phthalates induces reduced AGD and malformations in male rats (Mylchreest et al, 1999;Gray et al, 2000) Delay in pubertal development from exposure to PBBs Vaginal adenocarcinoma in young women due to DES (Herbst et al, 1971) ACE fetopathy with neonatal renal failure from maternal exposure to angiotensin inhibitors (Tabacova et al, 2003) Maternal smoking causes decreased birth weight and increased risk for later diabetes (Montgomery & Ekbom, 2002) and osteoporosis Decreased T3/T4 levels in infant and juvenile rats (Brouwer et al, 1998) exposed to PCBs (Birnbaum, 1995) Maternal grooming affects ability to respond to stress in adulthood in rats (Gilbert, 2005) Child Brain tumours and meningiomas...…”

Section: Introductionmentioning

confidence: 99%

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

Liu

Xia

Guo

et al. 2012

J Expo Sci Environ Epidemiol

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The urinary metabolites of phthalates are well-accepted exposure biomarkers for adults and children older than 6 years but are not commonly used for infants owing to non-convenient sampling. In the light of this situation, a novel sampling method based on monitoring the urine expressed from the gel diaper was developed. The urine was expressed from the gel absorbent after mixing the absorbent with CaCl2 and then collected by a laboratory-made device; the urinary phthalate metabolites were extracted and cleaned using a solid-phase extraction (SPE) column and analyzed with high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry / mass spectrometry. To evaluate the method's feasibility, the following factors were investigated: the proportion of CaCl2 to gel absorbent, the urination volume variation and the target compounds' deposition bias in the diaper, the matrix blank of the different diaper brands, the storage stabilities and the recoveries of creatinine and phthalate metabolites in the expressed urine. Mono-methyl phthalate, mono-ethyl phthalate, mono-butyl phthalate, mono-benzyl phthalate, mono-2-ethylhexyl phthalate and mono-2-ethyl-5-oxohexyl phthalate were involved. 70-80% of the urine can be expressed from the diaper, and the expressed spiking recoveries and the limit of detection of mono-phthalates ranged from 88.5-115% and 0.21-0.50 ng/ml. The method was applied to measure phthalate metabolites in 65 gel diaper samples from 15 infants, and the pilot data suggests the infants are commonly exposed to phthalates. In summary, the method for monitoring of infant exposure to phthalates is sound and validated, and the potential health effects from the vulnerable infants' exposure to phthalates should be concerned.39th Scientific Research Foundation for the Returned Overseas Chinese Scholars (SRF for ROCS); Hundred Talent Program of Chinese Academy of Sciences (CAS); CAS/SAFEA International Partnership Program for Creative Research Teams [KZCX2-YW-T08

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“…Since 1992, the U.S. Food and Drug Administration has required a warning on all ACEIs regarding their fetotoxic effects when used during trimesters two and three [16,17]. The specific features of ACEI fetopathy (positional limb deformities, retarded ossification of the skull, hypoplastic lungs) have been described as secondary to oligohydramnios that in turn is secondary to fetal renal dysfunction [18]. These effects were not seen when ACEI use was limited to the first trimester.…”

Section: Introductionmentioning

confidence: 99%

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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Adverse pregnancy outcomes associated with maternal enalapril antihypertensive treatment

Abstract: The specificity and temporality of the observed adverse manifestations suggest a causal relationship to enalapril exposure.

Cited by 107 publications

References 33 publications

Obstetric Nephrology

Obstetric Nephrology

Expressing urine from a gel disposable diaper for biomonitoring using phthalates as an example

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

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