Is there an embryopathy associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence

Polifka, Janine E.

doi:10.1002/bdra.23027

Cited by 37 publications

(20 citation statements)

References 182 publications

(76 reference statements)

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“…Because of their teratogenicity, the need to discontinue drugs that act on the renin-angiotensin system complicates the management of proteinuric patients (44,45).…”

Section: Discussionmentioning

confidence: 99%

Association of Low-Protein Supplemented Diets with Fetal Growth in Pregnant Women with CKD

Piccoli¹,

Leone²,

Attini

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Women affected by CKD increasingly choose to get pregnant. Experience with lowprotein diets is limited. The aim of this study was to review results obtained from pregnant women with CKD on supplemented vegan-vegetarian low-protein diets.Design, setting, participants, & measurements This was a single-arm, open intervention study between 2000-2012 of a low-protein diet in pregnant patients with stages 3-5 CKD or severe proteinuria (.1 g/d in the first trimester or nephrotic at any time). Stages 3-5 CKD patients who were not on low-protein diets for clinical, psychologic, or logistic reasons served as controls. The setting was the Obstetrics-Nephrology Unit dedicated to kidney diseases in pregnancy. The treated group included 24 pregnancies-21 singleton deliveries, 1 twin pregnancy, 1 abortion, and 1 miscarriage. Additionally, there were 21 controls (16 singleton deliveries, 5 miscarriages). The diet was a vegan-vegetarian low-protein diet (0.6-0.8 g/kg per day) with keto-acid supplementation and 1-3 proteinunrestricted meals allowed per week.Results Treated patients and controls were comparable at baseline for median age (35 versus 34 years), referral week (7 versus 8), eGFR (59 versus 54 ml/min), and hypertension (43.5% versus 33.3%); median proteinuria was higher in patients on the low-protein diet (1.96 [0.1-6.3] versus 0.3 [0.1-2.0] g/d; P,0.001). No significant differences were observed in singletons with regard to gestational week (34 versus 36) or Caesarean sections (76.2% versus 50%). Kidney function at delivery was not different, but proteinuria was higher in the diet group. Incidence of small for gestational age babies was significantly lower in the diet group (3/21) versus controls (7/16; chi-squared test; P=0.05). Throughout follow-up (6 months to 10 years), hospitalization rates and prevalence of children below the third percentile were similar in both groups.Conclusion Vegan-vegetarian supplemented low-protein diets in pregnant women with stages 3-5 CKD may reduce the likelihood of small for gestational age babies without detrimental effects on kidney function or proteinuria in the mother.

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“…Because of their teratogenicity, the need to discontinue drugs that act on the renin-angiotensin system complicates the management of proteinuric patients (44,45).…”

Section: Discussionmentioning

confidence: 99%

Association of Low-Protein Supplemented Diets with Fetal Growth in Pregnant Women with CKD

Piccoli¹,

Leone²,

Attini

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Epidemiological studies demonstrated an increased risk of congenital malformations among neonates of mothers who received ACEIs and ARBs during pregnancy compared to controls. 137 Several RCTs compared different antihypertensive drugs in pregnancy. A Cochrane systematic review included 24 RCTs that compared at least two antihypertensive drugs.…”

Section: Severe Hypertensionmentioning

confidence: 99%

Pregnancy-Induced hypertension

et al. 2015

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pregnancy-induced hypertension (pIh) complicates 6-10% of pregnancies. It is defined as systolic blood pressure (sbp) >140 mmhg and diastolic blood pressure (dbp) >90 mmhg. It is classified as mild (sbp 140-149 and dbp 90-99 mmhg), moderate (sbp 150-159 and dbp 100-109 mmHg) and severe (SBP ≥160 and DBP ≥110 mmHg). PIH refers to one of four conditions: a) pre-existing hypertension, b) gestational hypertension and preeclampsia (pe), c) pre-existing hypertension plus superimposed gestational hypertension with proteinuria and d) unclassifiable hypertension. pIh is a major cause of maternal, fetal and newborn morbidity and mortality. women with pIh are at a greater risk of abruptio placentae, cerebrovascular events, organ failure and disseminated intravascular coagulation. fetuses of these mothers are at greater risk of intrauterine growth retardation, prematurity and intrauterine death. ambulatory blood pressure monitoring over a period of 24 h seems to have a role in predicting deterioration from gestational hypertension to pe. antiplatelet drugs have moderate benefits when used for prevention of pe. treatment of pIh depends on blood pressure levels, gestational age, presence of symptoms and associated risk factors. non-drug management is recommended when sbp ranges between 140-149 mmhg or dbp between 90-99 mmhg. blood pressure thresholds for drug management in pregnancy vary between different health organizations. according to 2013 esh/esc guidelines, antihypertensive treatment is recommended in pregnancy when blood pressure levels are ≥150/95 mmHg. Initiation of antihypertensive treatment at values ≥140/90 mmHg is recommended in women with a) gestational hypertension, with or without proteinuria, b) pre-existing hypertension with the superimposition of gestational hypertension or c) hypertension with asymptomatic organ damage or symptoms at any time during pregnancy. methyldopa is the drug of choice in pregnancy. atenolol and metoprolol appear to be safe and effective in late pregnancy, while labetalol has an efficacy comparable to methyldopa. angiotensin-converting enzyme (ace) inhibitors and angiotensin II antagonists are contraindicated in pregnancy due to their association with increased risk of fetopathy.

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“…These deleterious effects have been confirmed in animal studies. Women of childbearing age under these treatments should be informed of the potential teratogenic and fetotoxic risks of these drugs if they become pregnant [ 91 ]. Data related to the use of β-blockers during pregnancy are limited.…”

Section: Medical Treatment In Pregnant Womenmentioning

confidence: 99%