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.
Objectives:
Our aim was to evaluate the effects of beta-blockers during the second and third trimester on fetal growth, length of gestation and postnatal symptoms in exposed infants.
Methods:
The current prospective observational cohort study compares 294 neonates of hypertensive mothers on metoprolol or bisoprolol during the second and/or third trimester with 225 methyldopa-exposed infants and 588 infants of nonhypertensive mothers. The risks for reduced birth weight, prematurity, neonatal bradycardia, hypoglycaemia and respiratory disorders were analysed.
Results:
The rate of small-for-gestational-age children was significantly higher in long-term beta-blocker exposed infants (24.1%) compared with the methyldopa cohort [10.2%, odds ratio (OR)adj 2.5, 95% confidence interval (CI) 1.2–5.2] and the nonhypertensive cohort (9.9%, ORadj 4.3, 95% CI 2.6–7.1). The risk for preterm birth was significantly increased compared with nonhypertensive pregnancies (ORadj 2.2, 95% CI 1.3–3.8) but not compared with the methyldopa cohort. Neonatal adverse outcomes occurred more frequently in the study cohort (11.5%) compared with the nonhypertensive comparison group (6.5%) and the methyldopa cohort (8.4%), but without statistical significance (ORadj 1.5, 95% CI 0.7–3.0 and ORadj 1.5, 95% CI 0.7–3.3, respectively).
Conclusion:
Long-term intrauterine exposure to metoprolol or bisoprolol may increase the risk of being born small-for-gestational-age. It is still a matter of debate to which extent maternal hypertension contributes to the lower birth weight. Serious neonatal symptoms are rare. Altogether, metoprolol and bisoprolol are well tolerated treatment options, but a case-by-case decision on close neonatal monitoring is recommended.
Our study supports the hypothesis that first trimester bisoprolol treatment does not increase the risk for spontaneous abortions or major birth defects. However, an influence of prolonged bisoprolol exposure on fetal growth cannot be ruled out.
Our 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.
We report on a rare case of a late-onset drug-induced lupus erythematosus. A 35 year old male patient complained about dyspnea, chest pain and reduced physical activity for three months. His medical history consisted of epilepsy treated with carbamazepine for 20 years. After diagnosis of a large pericardial effusion and percardiocentesis (1200 ml) the diagnosis of viral perimyocarditis was suspected. Under antiphlogistic treatment the symptoms vanished initially. Four weeks later the pericardial effusion recurred and a livedo reticularis became evident. A structural or infectious heart disease, in particular viral myocarditis, was ruled out invasively. Serologic testing revealed antinuclear antibodies and antibodies against histones without presence of antibody against ds-DNA, thereby confirming the diagnosis of carbamazepine-induced lupus erythematodes. After discontinuation of carbamazepine and immunosuppressive medication the patient recovered completely.
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