In-utero exposure to antihypertensive medication and neonatal and child health outcomes:A systematic review

Background: Although medication is generally avoided wherever possible during pregnancy, pharmacotherapy is required for the treatment of pregnancy associated hypertension, which remains a leading cause of maternal and fetal morbidity and mortality. The long-term effects to the child of in-utero exposure to antihypertensive agents remains largely unknown. Objective: The aim of this study was to systematically review published studies on adverse outcomes to the child associated with in-utero exposure to antihypertensive medications. Methods: OVID, Scopus, EBSCO Collections, the Cochrane Library, and Web of Science databases were searched for relevant publications published between January 1950 and October 2016 and a total of 688 potentially eligible studies were identified. Results: Following review, 47 primary studies were eligible for inclusion. The Critical Appraisal Skills Programme checklist was used to assess study quality. Five studies were of excellent quality; the remainder were either mediocre or poor. Increased risk of low birth weight, low size for gestational age, preterm birth, and congenital defects following in-utero exposure to all antihypertensive agents were identified. Two studies reported an increased risk of attention deficit hyperactivity disorder following exposure to labetalol, and an increased risk of sleep disorders following exposure to methyldopa and clonidine. Conclusion: The current systematic review demonstrates a paucity of relevant published high-quality studies. A small number of studies suggest possible increased risk of adverse child health outcomes; however, most published studies have methodological weaknesses and/or lacked statistical power thus preventing any firm conclusions being drawn

Endothelin-Dependent Vasoconstriction in Human Uterine Artery: Application to Preeclampsia

BACKGROUND: Reduced uteroplacental perfusion, the initiating event in preeclampsia, is associated with enhanced endothelin-1 (ET-1) production which feeds the vasoconstriction of uterine artery. Whether the treatments of preeclampsia were effective on ET-1 induced contraction and could reverse placental ischemia is the question addressed in this study. We investigated the effect of antihypertensive drugs used in preeclampsia and of ET receptor antagonists on the contractile response to ET-1 on human uterine arteries. METHODOLOGY/PRINCIPAL FINDINGS: Experiments were performed, ex vivo, on human uterine artery samples obtained after hysterectomy. We studied variations in isometric tension of arterial rings in response to the vasoconstrictor ET-1 and evaluated the effects of various vasodilators and ET-receptor antagonists on this response. Among antihypertensive drugs, only dihydropyridines were effective in blocking and reversing the ET-1 contractile response. Their efficiency, independent of the concentration of ET-1, was only partial. Hydralazine, alpha-methyldopa and labetalol had no effect on ET-1 induced contraction which is mediated by both ET(A) and ET(B) receptors in uterine artery. ET receptors antagonists, BQ-123 and BQ-788, slightly reduced the amplitude of the response to ET-1. Combination of both antagonists was more efficient, but it was not possible to reverse the maximal ET-1-induced contraction with antagonists used alone or in combination. CONCLUSION: Pharmacological drugs currently used in the context of preeclampsia, do not reverse ET-1 induced contraction. Only dihydropyridines, which partially relax uterine artery previously contracted with ET-1, might offer interesting perspectives to improve placental perfusion

Hemodynamic and metabolic effects after nifedipine and ritodrine tocolysis

Objectives: The purpose of this study is to compare the hemodynamic and metabolic changes after ritodrine and nifedipine tocolysis. Methods: For an open randomized study, patients with preterm labor (N=185) were allocated to groups to receive ritodrine intravenously (N=90) or nifedipine orally (N=95). Results: The mean diastolic blood pressure was significantly lower in the ritodrine group 24 h (65±12 vs. 70±8, P=0.001) and 48 h (65±12 vs. 71±8, P=0.004) after starting tocolysis compared with the nifedipine group. Mean maternal heart rate was significantly higher in the ritodrine group 24 h (105±17 vs. 86±13, P<0.0001) and 48 h (100±21 vs. 85±12, P<0.0001) after starting tocolysis compared with the nifedipine group. Mean fasting glucose levels were higher (6.68±2.53 vs. 4.93±1.23, P=0.0016), while mean potassium levels were lower (3.52±0.84 vs. 3.81±0.45, P=0.04) in the ritodrine group 48 h after starting tocolysis compared with the nifedipine group. Conclusions: Use of nifedipine for preterm labor is associated with a lower incidence of adverse hemodynamic and metabolic changes compared with ritodrine after 24 and 48 h of tocolysis. In our opinion nifedipine is the preferred drug of choice for the treatment of preterm labor.D. N. M. Papatsonis, H. P. van Geijn, O. P. Bleker, H. J. Adèr and G. A. Dekke

Independent Determinants of Maternal and Fetal Outcomes in a Sample of Pregnant Outpatients With Normal Blood Pressure, Chronic Hypertension, Gestational Hypertension, and Preeclampsia

The aim of this retrospective study was to evaluate the main independent prognostic factors of negative maternal and fetal outcomes in a relatively large sample of pregnant outpatients (N=906) who were normotensive or affected by chronic hypertension, gestational hypertension, or preeclampsia. Among the studied parameters, the ones significantly associated with negative maternal outcomes were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and higher serum uric acid level, while antihypertensive treatment, number of previous deliveries, and blood pressure (BP) control at deliveries seemed to be protective. Regarding negative fetal outcomes, the parameters significantly associated with a negative maternal outcome were a diagnosis of preeclampsia (vs other forms of hypertension or normotension) and mother pre-pregnancy body mass index, while antihypertensive treatment and BP control at delivery seemed to be protective. Specific patient characteristics should help to predict the risk of negative maternal and fetal outcomes