Pregnancy Outcome After First Trimester Use of Methyldopa

Abstract

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.

Management of hypertension in pregnancy — prevention, diagnosis, treatment and long-term prognosis. A position statement of the Polish Society of Hypertension, Polish Cardiac Society and Polish Society of Gynaecologists and Obstetricians

“…On the other hand, the analysis of the German pharmacovigilance database showed that the exposure to methyldopa in the first trimester was associated with a higher incidence of adverse maternal and perinatal outcomes. However, the outcome analysis in that study did not control for the effect of blood pressure values [70]. The results of both studies support the conclusion that the need for antihypertensive treatment in the first trimester (when blood pressure tends to decrease physiologically) may indicate higher severity of HT and the associated increased risk of maternal and perinatal complications.…”

“…Methyldopa, a centrally active sympatholytic agent (an antagonist to the a2 adrenergic receptor), has long been used in the treatment of HT in pregnancy and has an established safety record with a 7-year follow-up of child development following in utero exposure [71]. It can be used in pregnancy from the first trimester [70]. However, sedative effect and excessive sleepiness, as well as potential hepatotoxicity (usually transient elevation of liver function markers) limit its use.…”

Pre-eclampsia with severe features: management of antihypertensive therapy in the postpartum period

“…Alpha methyldopa was most commonly used antenatally. This is related to its long-standing history of safety profile in pregnancy [ 16 ]. This prescription is in agreement with current guidelines [ 27 ].…”

“…Before these findings, antihypertensive drug therapy in PE without severe features was thought to reduce fetal perfusion [ 13 ] but may be prescribed based on indication [ 13 , 14 ]. Studies in the prenatal period have improved the use of antenatal antihypertensive agents [ 15 ] and in many countries especially in low- and middle-income countries, the first-line antihypertensive drug during this period is alpha-methyldopa [ 16 ]. In the postpartum period, only limited data are available to guide the drug management of hypertension [ 17 - 19 ].…”

The management of hypertension in women planning for pregnancy

“…Methyldopa is often considered the first-line therapy for pre-pregnancy antihypertensive treatment 24 , 25 with the largest quantity of data regarding fetal safety since it has been used for pregnancy hypertension since 1960s 26 even in the first trimester. 27 In a 7.5-year follow-up study, there were no adverse growth or developmental outcomes in children whose mothers received methyldopa during pregnancy. 28 Many clinicians opt to change women’s antihypertensive therapy to methyldopa prior to conception, especially if they require more than one drug and it is unlikely that they will be able to discontinue therapy in early pregnancy.…”