Anne-Katrin Fietz

Pregnancy Outcome After First Trimester Use of Methyldopa: A Prospective Cohort Study.

Published experience on first trimester exposure to methyldopa is still limited, although it is recommended as first-line treatment for hypertensive disorders in pregnancy in most countries. The primary aim of this prospective observational cohort study was to analyze the rate of major birth defects and spontaneous abortions in women with methyldopa therapy for chronic hypertension. Outcomes of 261 pregnancies with first trimester exposure to methyldopa and 526 comparison pregnancies without chronic hypertension reported to the German Embryotox pharmacovigilance institute were evaluated. The rate of major birth defects in the exposed cohort was not significantly increased compared with the comparison cohort (3.7% versus 2.5%; adjusted odds ratio, 1.24; 95% confidence interval, 0.4–4.0). There was a tendency toward a higher rate of spontaneous abortions in exposed women. The risk of preterm birth was significantly higher, and adjusted birth weight scores were significantly lower in the methyldopa group. Head circumferences were significantly reduced in exposed boys only. There was neither evidence for an increased risk for birth defects or increase in early pregnancy loss nor evidence for growth restriction or a reduced head circumference in a sensitivity analysis comparing monotherapies with methyldopa to metoprolol. However, the significantly increased risk of preterm birth in methyldopa-treated pregnancies was confirmed. In conclusion, our study does not indicate a teratogenic risk of methyldopa. Further studies are needed to confirm its safety in the first trimester and clarify the influence of hypertension and methyldopa on preterm birth and intrauterine growth. Clinical Trial Registration— URL: https://drks-neu.uniklinik-freiburg.de/drks_web/. Unique identifier: DRKS00010502.

Pregnancy outcome after first trimester use of angiotensin AT1 receptor blockers: an observational cohort study

BackgroundOngoing discussion about the safety of renin–angiotensin inhibitors in the first trimester and limited data on pregnancy outcomes after exposure to angiotensin AT1 receptor blockers (ARBs).MethodsObservational cohort study compares outcomes of 215 prospectively ascertained pregnancies with first trimester exposure to ARBs with 642 non-hypertensive pregnancies.ResultsThe rate of major birth defects in the ARB cohort (9/168, 5.4%) was higher than in the comparison group (17/570, 3%), but not significantly increased (ORadj 1.9, 95% CI 0.7–4.9). There was no distinct pattern of anomalies among infants with birth defects. The risk of spontaneous abortions was not increased (HRadj 0.9, 95% CI 0.5–1.6), although the cumulative incidence was in the upper normal range (0.22, 95% CI 0.15–0.32). Higher rates of prematurity (ORadj 3.0; 95% CI 1.7–5.1) and a reduced birth weight after adjustment for sex and gestational age were observed. There was no evidence for an increased risk for major birth defects, spontaneous abortions, or preterm birth in a sensitivity analysis comparing ARB exposed hypertensive women to hypertensive women without ARB exposure during the first trimester.ConclusionOur study supports the hypothesis that ARBs are not major teratogens. Patients inadvertently exposed to ARBs during the early pregnancy may be reassured. Nevertheless, women planning pregnancy should avoid ARBs. In selected cases, ARBs might be continued under careful monitoring of menstrual cycle and discontinued as soon as pregnancy is recognized.

No evidence of adverse pregnancy outcome after exposure to ibuprofen in the first trimester – Evaluation of the national Embryotox cohort

Ibuprofen is an analgesic frequently used in the 1st and 2nd trimester of pregnancy. Most relevant studies deal with NSAID as a group and do not specifically focus on ibuprofen. In this study, 1117 women exposed to ibuprofen in the 1st trimester were compared to 2229 non-exposed women. Data were retrieved from the German Embryotox database. No significantly increased risk of major birth defects (4.8% vs. 4.1%; OR adjusted 1.11, 95% CI 0.75-1.64) or a distinct pattern of birth defects were found. The cumulative incidences of spontaneous abortions were similar across cohorts (15.5% vs. 16.6%; HR adjusted 0.85; 95% CI, 0.65-1.11). Subgroup analyses of pregnancies exposed for ≥7 (nu202f=u202f223) and ≥30u202fdays (nu202f=u202f72) did not reveal a higher risk with increasing treatment duration. Ibuprofen does not seem to carry a substantial embryotoxic risk regarding the investigated endpoints.

Increased rate of birth defects after first trimester use of angiotensin converting enzyme inhibitors – Treatment or hypertension related? An observational cohort study

OBJECTIVESnTo analyze the risk of spontaneous abortions and major birth defects in pregnancies of women treated with angiotensin converting enzyme inhibitors (ACEIs) during the first trimester.nnnSTUDY DESIGNnObservational cohort study of prospectively ascertained pregnancies from the German Embryotox pharmacovigilance institute. Pregnancy outcomes after maternal exposure to ACEIs during the first trimester were compared with pregnancies without antihypertensive treatment. In a sensitivity analysis, ACEI exposed hypertensive women were compared with hypertensive women on methyldopa.nnnRESULTSnThe risk of spontaneous abortion among 329 ACEI exposed women was not increased compared to 654 women without antihypertensive treatment (adjusted hazard ratio 1.20, 95% confidence interval (CI) 0.74-1.92), whereas the risk for major birth defects (14/255; 5.5% vs. 19/567; 3.4%) was significantly increased (adjusted odds ratio 2.41, 95% CI 1.07-5.43). In contrast, birth defect rates were not significantly different between hypertensive women on ACEIs and hypertensive women on methyldopa. In addition, we did not observe a distinct pattern of birth defects among retrospectively ascertained pregnancies after ACEI exposure during the first trimester.nnnCONCLUSIONSnWomen with hypertension treated with ACEIs in early pregnancy are at higher risk for major birth defects, which may be explained by other factors associated with maternal hypertension. Women (inadvertently) exposed during early pregnancy may be reassured and treatment switched to antihypertensive drugs recommended for pregnancy.

Exposure to cox-2 inhibitors (coxibs) during the first trimester and pregnancy outcome: a prospective observational cohort study

PurposeCox-2-inhibitors (coxibs) are not recommended in pregnancy but early exposure may occur, for instance in unplanned pregnancies. Experience in pregnancy is limited leading to concerns in patients and their health care providers. Therefore, further data on coxibs and their effects on embryogenesis are needed.MethodsThis observational cohort study evaluates pregnancies ascertained in Germany during the study period from January 2000 to January 2016. A cohort of 174 women exposed to coxibs in the first trimester was compared to a randomly selected cohort of 521 women without exposure to coxibs, other nonsteroidal anti-inflammatory drugs or known teratogens.ResultsThe overall rate of major birth defects was not significantly increased in the study cohort (2.9 vs. 2.7%, OR 1.08, 95% CI 0.34–3.42; OR adjusted 0.96, 95% CI 0.28–3.26). The cumulative incidence of spontaneous abortions was nonsignificantly lower in the exposed cohort (14.3 vs. 20.0%; HR, 0.90, 95% CI 0.51–1.58; HR adjusted, 0.87; 95% CI, 0.49–1.56). Elective terminations of pregnancies (ETOP), mainly for ‘social’ reasons, were more frequent in the coxib cohort (17.5 vs. 7.0%, HR, 2.31; 95% CI, 1.26–4.24; HR adjusted 2.12, 95% CI 1.13–3.97).ConclusionsOur study results support the assumption that coxibs are not major teratogens. Considering the still limited evidence basis on coxib exposure during pregnancy, well-established alternatives should be preferred.

OP 27 Methyldopa during the first trimester and pregnancy outcome – A prospective observational cohort study

Introduction An increased risk of congenital malformations in offspring of mothers with chronic hypertension is discussed. Although methyldopa is recommended as first line treatment for hypertensive disorders in pregnancy in most countries, published experience on 1st trimester exposure is still limited. Objectives The primary aim of our study was to analyze the risk of birth defects and spontaneous abortions in women treated with methyldopa during the first trimester. Patients and methods The pattern of antihypertensive drug regimen during the first trimester was analyzed in 1152 prospectively ascertained pregnancies reported to the German Embryotox pharmacovigilance institute. Pregnancy outcomes were then evaluated in a subgroup of women treated with methyldopa ( n xa0=xa0261) and compared to a non-hypertensive comparison group ( n xa0=xa0526). Results At conception 51% of women were treated with beta-blockers, 47% with RAAS-inhibitors and only 14% with methyldopa; monotherapy with one antihypertensive drug occured in 66% of pregnancies. The rate of major birth defects among women exposed to methyldopa during 1st trimester was not significantly increased compared to non-hypertensive women (3.7% vs. 2.5%; ORadj 1.24, 95% CI 0.4–4.0). There was a tendency towards a higher rate of spontaneous abortions in methyldopa exposed women. The risk of preterm birth was significantly higher and adjusted birth weight scores were significantly lower in the methyldopa group. Head circumferences were significantly reduced in exposed boys only. In a sensitivity analysis comparing pregnancies methyldopa monotherapy to metoprolol monotherapy, there was neither evidence for an increased risk for birth defects or early pregnancy loss nor for growth restriction or a reduced head circumference. However, the significantly increased risk of preterm birth in methyldopa treated pregnancies was confirmed. Conclusions Our study supports the evidence of safety of methyldopa during pregnancy. Further studies are needed to clarify the influence of hypertension and treatment with antihypertensives on preterm birth and intrauterine growth. This work was performed with financial support from the German Ministry of Health (BMG) and the German Federal Institute for Drugs and Medical Devices (BfArM).

Pregnancy Outcome After First Trimester Use of Methyldopa

Published experience on first trimester exposure to methyldopa is still limited, although it is recommended as first-line treatment for hypertensive disorders in pregnancy in most countries. The primary aim of this prospective observational cohort study was to analyze the rate of major birth defects and spontaneous abortions in women with methyldopa therapy for chronic hypertension. Outcomes of 261 pregnancies with first trimester exposure to methyldopa and 526 comparison pregnancies without chronic hypertension reported to the German Embryotox pharmacovigilance institute were evaluated. The rate of major birth defects in the exposed cohort was not significantly increased compared with the comparison cohort (3.7% versus 2.5%; adjusted odds ratio, 1.24; 95% confidence interval, 0.4–4.0). There was a tendency toward a higher rate of spontaneous abortions in exposed women. The risk of preterm birth was significantly higher, and adjusted birth weight scores were significantly lower in the methyldopa group. Head circumferences were significantly reduced in exposed boys only. There was neither evidence for an increased risk for birth defects or increase in early pregnancy loss nor evidence for growth restriction or a reduced head circumference in a sensitivity analysis comparing monotherapies with methyldopa to metoprolol. However, the significantly increased risk of preterm birth in methyldopa-treated pregnancies was confirmed. In conclusion, our study does not indicate a teratogenic risk of methyldopa. Further studies are needed to confirm its safety in the first trimester and clarify the influence of hypertension and methyldopa on preterm birth and intrauterine growth. Clinical Trial Registration— URL: https://drks-neu.uniklinik-freiburg.de/drks_web/. Unique identifier: DRKS00010502.

Pregnancy Outcome After First Trimester Use of MethyldopaNovelty and Significance: A Prospective Cohort Study

Published experience on first trimester exposure to methyldopa is still limited, although it is recommended as first-line treatment for hypertensive disorders in pregnancy in most countries. The primary aim of this prospective observational cohort study was to analyze the rate of major birth defects and spontaneous abortions in women with methyldopa therapy for chronic hypertension. Outcomes of 261 pregnancies with first trimester exposure to methyldopa and 526 comparison pregnancies without chronic hypertension reported to the German Embryotox pharmacovigilance institute were evaluated. The rate of major birth defects in the exposed cohort was not significantly increased compared with the comparison cohort (3.7% versus 2.5%; adjusted odds ratio, 1.24; 95% confidence interval, 0.4–4.0). There was a tendency toward a higher rate of spontaneous abortions in exposed women. The risk of preterm birth was significantly higher, and adjusted birth weight scores were significantly lower in the methyldopa group. Head circumferences were significantly reduced in exposed boys only. There was neither evidence for an increased risk for birth defects or increase in early pregnancy loss nor evidence for growth restriction or a reduced head circumference in a sensitivity analysis comparing monotherapies with methyldopa to metoprolol. However, the significantly increased risk of preterm birth in methyldopa-treated pregnancies was confirmed. In conclusion, our study does not indicate a teratogenic risk of methyldopa. Further studies are needed to confirm its safety in the first trimester and clarify the influence of hypertension and methyldopa on preterm birth and intrauterine growth. Clinical Trial Registration— URL: https://drks-neu.uniklinik-freiburg.de/drks_web/. Unique identifier: DRKS00010502.