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Teratogenic Risk (teratogenic + risk)
Selected AbstractsSafety of medications prescribed before and during early pregnancy in a cohort of 81,975 mothers from the UK General Practice Research Database,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 8 2006Janet R. Hardy PhD Abstract Purpose To demonstrate a linkage methodology for mother and baby automated medical records, and describe frequency, type, and pregnancy risk level of medications prescribed during pregnancy in a GPRD cohort, 1991,1999. Methods We linked records using a two-stage algorithm and selected pairs with ,7 months prenatal records and ,2 records in baby's first year of life. Periods of interest were: 90 days prior to a woman's earliest identified pregnancy record (Period I), and this record plus 70 days (Period II, approximate early pregnancy). Medications were classified using the British National Formulary and US Food and Drug Administration Pregnancy Risk Categories. Results We achieved over 80% record linkage and defined a cohort of 81,975. Sixty-five per,cent of mothers had ,1 prescription during both periods combined. Most frequent medications in Period I were anti-bacterial, contraceptive, topical steroid, and bronchodilator. In Period II, they were folic acid, anti-bacterial, antacid, and gynecological anti-infective. In Period I, 4% were FDA category A (considered safest), 34% B, and 49% C and D combined. By Period II, prescription of category A medications increased (folic acid, iron) while other categories declined. Category X medications, with potential teratogenic risk that outweighs maternal benefit, were prescribed to 5714 (7%) women in Period I, and 501 (0.6%) women in Period II (46% progesterone). Conclusions One in every 164 women received a category X prescription in early pregnancy. The visit when pregnancy is first medically recognized represents an opportunity to review prescribed medications in light of contraindication and/or fetal risk. Copyright © 2006 John Wiley & Sons, Ltd. [source] Variability in human embryonic development and its implications for the susceptibility to environmental teratogenesisBIRTH DEFECTS RESEARCH, Issue 8 2009Kohei Shiota Abstract Considerable variability is observed in the size and developmental stage among human embryos at a given gestational age, suggesting that prenatal development does not proceed at the same speed in every embryo. Such variability in embryonic development seems to occur in many (probably all) animal species, and is probably a normal "biologic" phenomenon to some extent. In the case of humans, some other factors (e.g., maternal memory bias, difficulty in assessing the timing of ovulation and fertilization) make it more difficult to assess the developmental stage of embryos in utero. Such facts related to human embryonic development should be taken into account when the teratogenic risk of a human embryo is considered. Birth Defects Research (Part A), 2009. © 2009 Wiley-Liss, Inc. [source] Is lack of morning sickness teratogenic?BIRTH DEFECTS RESEARCH, Issue 8 2004A prospective controlled study BACKGROUND Case-control studies have suggested that the nausea and vomiting of pregnancy (NVP) may have a protective effect against specific malformations. These suggestions have been interpreted as if the lack of NVP may put mothers at an increased teratogenic risk. METHODS A prospective, cohort-controlled study was done comparing pregnancy outcome in women not experiencing NVP with those experiencing NVP at two levels of clinical severity. Women who called the Motherisk program about first-trimester exposure to drugs and who had not experienced NVP were included as the study group. The NVP Healthline enrolled two control groups of women with NVP treated with a doxylamine-pyridoxine combination for morning sickness. These women were exposed during the first trimester of gestation to either higher than the standard dose (5,12 tablets/day) or a standard dose (1,4 tablets/day) of doxylamine-pyridoxine. The women in all three groups were followed up four to six months after the expected date of birth to ascertain pregnancy outcomes and child health. RESULTS There were no major malformations among offspring of 130 women not experiencing NVP. There were two major malformations among 246 women experiencing NVP. The two control groups of women with NVP had similar distributions of gestational ages, birth rates, as well as rates of miscarriages and stillbirths, as in the no-NVP group. CONCLUSIONS This study did not show an association between lack of NVP and an increase in the overall rates of major malformations. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] Classification of drugs for teratogenic risk: An anachronistic way of counseling: A reply to Merlob and StahlBIRTH DEFECTS RESEARCH, Issue 3 2003Gerald G. Briggs [source] Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational studyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2008Orna Diav-Citrin WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , In recent years there has been concern regarding the possibility that selective serotonin reuptake inhibitors (SSRIs) cause an increased rate of congenital cardiovascular anomalies. , As of today, there is still debate in the literature as to the possible effects of paroxetine and fluoxetine on the embryonic cardiovascular system. WHAT THIS STUDY ADDS , Based on prospective data from three Teratogen Information Services, we have demonstrated an increased rate of congenital cardiovascular anomalies among the offspring of fluoxetine- and paroxetine-treated mothers. AIMS Recent studies have suggested a possible association between maternal use of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy and cardiovascular anomalies. The aim of the present study was to evaluate the teratogenic risk of paroxetine and fluoxetine. METHODS This multicentre, prospective, controlled study evaluated the rate of major congenital anomalies after first-trimester gestational exposure to paroxetine, fluoxetine or nonteratogens. RESULTS We followed up 410 paroxetine, 314 fluoxetine first-trimester exposed pregnancies and 1467 controls. After exclusion of genetic and cytogenetic anomalies, there was a higher rate of major anomalies in the SSRI groups compared with the controls [paroxetine 18/348 (5.2%), fluoxetine 12/253 (4.7%) and controls 34/1359 (2.5%)]. The main risk applied to cardiovascular anomalies [paroxetine 7/348 (2.0%), crude odds ratio (OR) 3.47, 95% confidence interval (CI) 1.13, 10.58; fluoxetine 7/253 (2.8%), crude OR, 4.81 95% CI 1.56, 14.71; and controls 8/1359 (0.6%)]. On logistic regression analysis only cigarette smoking of ,10 cigarettes day,1 and fluoxetine exposure were significant variables for cardiovascular anomalies. The adjusted ORs for paroxetine and fluoxetine were 2.66 (95% CI 0.80, 8.90) and 4.47 (95% CI 1.31, 15.27), respectively. CONCLUSION This study suggests a possible association between cardiovascular anomalies and first-trimester exposure to fluoxetine. [source] Teratogenicity of antiepileptic drugs: role of drug metabolism and pharmacogenomicsACTA NEUROLOGICA SCANDINAVICA, Issue 1 2007R. Sankar The approach to clinical decision-making pertaining to the use of antiepileptic drugs (AEDs) during pregnancy has relied on previous accumulated experience and, since the 1990s, on data from pregnancy registries. The limitations of this process are that no information regarding the chemical attributes of the AED under consideration, nor the role of a number of enzyme systems that are known to interact with foreign compounds to modify their potential for harm, are included. The role of the hepatic mixed function oxidase system may be especially important in conferring teratogenic risk. However, systems such as epoxide hydrolase, glutathione reductase, superoxide dismutase and other toxin-scavenging systems may be important modifiers that lower the risk. Knowledge is also accumulating on the interactions of AEDs with molecular targets such as histone deacetylase and peroxisome proliferator-activated receptors that may play important roles in teratogenesis. While our knowledge of these factors are incomplete, progress can be achieved by beginning to include these concepts in our discussion on the topic and by promoting research that may improve our ability to individualize the analysis of risk for a specific patient with regards to specific AEDs. [source] Bipolar disorder in women: reproductive events and treatment considerationsACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2005M. P. Freeman Objective:, Bipolar disorders are prevalent in women. Women with bipolar disorder often present with different clinical features than men. Reproductive events and hormonal treatments may impact the course of bipolar disorder. Our main objectives are to i) assess the impact of reproductive events on the course of the disorder, and ii) to discuss the relationships between reproductive events and psychiatric treatments. Method:, A literature search was conducted of MEDLINE journals from 1965 to present. Manual literature searches were also conducted. We review the presentation, clinical course, and treatment considerations of bipolar disorder in women, with emphasis on treatment considerations in the context of reproductive events. Treatment-related issues such as teratogenicity, breastfeeding, polycystic ovarian syndrome, weight gain and obesity, and medication interactions with oral contraceptives are reviewed. Results:, Women with bipolar disorder may be more vulnerable to mood episodes in the context of reproductive events, particularly postpartum. In women of reproductive age, mood stabilizers must be selected with teratogenic risks in mind, with the highest reported risks in pregnancy with valproate, and the greatest concern during breastfeeding with lithium use. In the areas of the perimenopause and polycycstic ovarian syndrome, more data are needed to advise treatment decisions. Conclusion:, We urgently need further study in these areas to deliver care that is appropriate to women with bipolar disorder. [source] Navigating toward Fetal and Maternal Health: The Challenge of Treating Epilepsy in PregnancyEPILEPSIA, Issue 10 2004Torbjörn Tomson Summary:, A rational approach to the treatment of women of childbearing potential with epilepsy has been hampered by the lack of conclusive data on the comparative teratogenic potential of different antiepileptic drugs (AEDs). Although, several cohort studies on birth defects associated with AED use during pregnancy have been published, these have generally failed to demonstrate differences in malformation rates between AEDs, probably mainly due to insufficient power. In particular, pregnancies with new generation AEDs have been too few. In recent years, pregnancy registries have been introduced to overcome this problem,EURAP (an international collaboration), the North American, and the U.K. AED and pregnancy registries are observational studies that prospectively assess pregnancy outcome after AED exposure using slightly different methods. Each has enlisted 3,5,000 pregnancies in women with epilepsy, and the North American and the U.K. have released preliminary observations. Thus the U.K. registry reported a higher malformation rate with valproate, 5.9% (4.3,8.2%; 95% CI), than with carbamazepine, 2.3% (1.4,3.7%), and lamotrigine, 2.1% (1.0,4.0%). Most of the more recent cohort studies have also identified a nonsignificant trend toward a higher teratogenicity with valproate. These signals need to be interpreted with some caution since none of the studies to date have fully assessed the impact of possible confounders, such as type of epilepsy, family history of birth defects, etc. However, with increasing number of pregnancies it should be possible in the near future for the pregnancy registries to take such confounding factors into account and thus make more reliable assessments of the causal relationship between exposure to specific AEDs and teratogenic risks. While awaiting more conclusive results, it appears reasonable to be cautious in prescribing valproate to women considering to become pregnant if other suitable treatment alternatives, and with less teratogenic potential, are available. Any attempt to change treatment should, however, be accomplished well before conception. The importance of maintained seizure control must also be kept in mind, and the woman who needs valproate to control her seizures should not be discouraged from pregnancy, provided that counseling at the best of available knowledge is given. [source] | |||||||||||||||||||