Neurocognitive development of children following in-utero exposure to labetalol for maternal hypertension: a cohort study using a prospectively collected database.
ABSTRACT To identify the effect of prenatal labetalol exposure on children's long-term neurodevelopment.
A cohort study with matched controls using a prospectively collected database.
Participants were women counseled for hypertension in pregnancy at the Motherisk Program at The Hospital for Sick Children, and The Sunnybrook Health Sciences Centre, Toronto, Canada and their children. Mother-child pairs were divided into groups based on in-utero exposure to labetalol (n = 32), non-teratogenic substances (n = 42), and methyldopa (n = 25). The main outcome measures were children's Full-Scale IQ, Performance IQ and Verbal IQ assessed with the Wechsler Preschool and Primary Scale of Intelligence.
There were no statistically significant differences in scores on Full-Scale IQ, Performance IQ, or Verbal IQ between children exposed in utero to labetalol and to non-teratogenic substances (Full-Scale IQ: 109.60 +/- 8.20 vs. 111.90 +/- 11.39, p = 0.647; Performance IQ: 104.80 +/- 8.69 vs. 110.19 +/- 12.91, p = 0.186; Verbal IQ: 112.27 +/- 11.05 vs. 11.21 +/- 11.98, p = 0.922, respectively). Children in the methyldopa group achieved lower scores on measures of Full-Scale IQ and Performance IQ when compared to children exposed to non-teratogenic substances (Full-Scale IQ: 105.24 +/- 12.46 vs. 111.90 +/- 11.39, p = 0.043; Performance IQ: 98.80 +/- 16.16 vs. 110.19 +/- 12.91, p = 0.002, respectively). Linear regression analysis revealed that maternal Full Scale IQ was a significant predictor of children's Full-Scale IQ (p = 0.020, beta = 0.229). Maternal Performance IQ and duration of treatment with methyldopa were significant predictors of children's Performance IQ (p = 0.028, beta = 0.232; p = 0.16, beta = -0.255, respectively).
In-utero exposure to labetalol does not appear to adversely affect the neurocognitive development of young children. These reassuring results may aid disease management for pregnant women with hypertension.
- SourceAvailable from: Peter von Dadelszen[Show abstract] [Hide abstract]
ABSTRACT: Labetalol is one of the most commonly used antihypertensive medications for the treatment of hypertension during pregnancy, an increasingly common and leading cause of maternal mortality and morbidity worldwide. The literature reviewed included the 2014 Canadian national pregnancy hypertension guideline and its references. The additional published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, and postpartum follow-up).Results were restricted to systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies published in French or English, Jan-Mar/14. The unpublished literature was identified by searching websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. We evaluated the impact of interventions on substantive clinical outcomes for mothers and babies. Labetalol is a reasonable choice for treatment of severe or non-severe hypertension in pregnancy. However, we should continue our search for other therapeutic options.Expert Opinion on Drug Safety 03/2015; 14(3):453-61. DOI:10.1517/14740338.2015.998197 · 2.74 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Context. Envenomations during pregnancy pose all the problems of envenomation in the nonpregnant state with additional complexity related to maternal physiologic changes, medication use during pregnancy, and the well-being of the fetus. Objective. We review the obstetric literature and management options available to prevent maternal morbidity and mortality while limiting adverse obstetric outcomes after envenomation in pregnancy. Methods. In January 2012, we searched the U.S. National Library of Medicine Medline/PubMed, Toxline, Reprotox, Google Scholar and Micromedex databases, core surgery and internal medicine textbooks, and references of retrieved articles for the years 1966 through 2011. Search terms included "envenomation in pregnancy," "stings in pregnancy," "antivenom use in pregnancy," "anaphylaxis in pregnancy," and variants of these with known venomous animals. Reference lists generated further case reports and articles. We included English language articles and abstracts. Levels of Evidence (LOE) for the reports cited and Grades of Recommendations (GOR) based on LOE for our recommendations use the National Guidelines Clearinghouse metric of the US DHHS. Results. Recommendations for the management of envenomation in pregnancy are guided primarily by studies on nonpregnant persons and case reports of pregnancy. Clinically significant envenomations in pregnancy are reported for snakes, spiders, scorpions, jellyfish, and hymenoptera (bees, wasps, hornets, and ants). Adverse obstetric outcomes including miscarriage, preterm birth, placental abruption, and stillbirth are associated with envenomation in pregnancy. The limited available literature suggests that adverse outcomes are primarily related to venom effects on the mother. Optimization of maternal health such as management of anaphylaxis and antivenom administration is likely the best approach to improve fetal outcomes despite potential risks to the fetus of medication administration during pregnancy. Obstetric evaluation and fetal monitoring are imperative in cases of severe envenomation. Conclusion. The medical literature regarding envenomation in pregnancy includes primarily retrospective reviews and case series. The limited available evidence suggests that optimal management includes a venom-specific approach, including supportive care, antivenom administration in appropriate cases, treatment of anaphylaxis if present, and fetal assessment. The current available evidence suggests that antivenom use is safe in pregnancy and that what is good for the mother is good for the fetus. Further research is needed to clarify the optimal management schema for envenomation in pregnancy.Clinical Toxicology 01/2013; 51(1). DOI:10.3109/15563650.2012.760127 · 3.12 Impact Factor
Article: Therapeutics and anaesthesia[Show abstract] [Hide abstract]
ABSTRACT: Many aspects of hypertension care outside pregnancy may be applied in pregnancy, but little information is available on which to base decision-making. It would seem reasonable to continue previous dietary salt restriction and physical activity in women with pre-existing (and controlled) hypertension, encourage a heart-healthy diet in all women with a hypertension disorder of pregnancy, and take patient preference into account when deciding on place of care. Although bed rest has become a key part of obstetric practice and for care of women with a hypertension disorder of pregnancy, in particular, the evidence is lacking to support this practice. This may also increase thromboembolic risk. Antihypertensive treatment is strongly advised for women with severe hypertension. The most common agents are parenteral labetalol, hydralazine, or oral nifedipine capsules. Clinicians should familiarise themselves with multiple agents. Until the role of antihypertensive treatment for non-severe hypertension in pregnancy is clarified by ongoing research, clinicians should explicitly state an individual patient's blood pressure goal, which could reasonably be anywhere between 130/80 and 155/105 mmHg. Labetalol and methyldopa are used most commonly. Breastfeeding should be encouraged. Many risk factors for hypertension (e.g. obesity), as well as hospitalisation and pre-eclampsia, all increase the thromboembolic risk for pregnant women, and care providers should consider thromboprophylaxis in the appropriate setting. Finally, anaesthetists play a critical role in the management of women with a hypertension disorder of pregnancy, and should be involved earlier rather than later in the course of their care.Best practice & research. Clinical obstetrics & gynaecology 04/2011; 25(4):477-90. DOI:10.1016/j.bpobgyn.2011.01.009 · 3.00 Impact Factor