Drug Safety In Pregnancy Research Articles

Hypertensive disorders of pregnancy

sUMMArY Hypertensive disorders of pregnancy are common and represent a spectrum of disease ranging from chronic and gestational hypertension to eclampsia. They are associated with increased risk of both adverse maternal and fetal outcomes. Drug treatment is generally reserved for moderate or severe hypertension. Pre-eclampsia–eclampsia can be life-threatening and requires urgent investigation and intervention. There are limited data about the safety of many hypertensive drugs in pregnancy. ACE inhibitors and angiotensin receptor blockers should be avoided.

Drug safety in pregnancy - monitoring congenital anomalies

This paper outlines research into the causes of congenital anomalies, and introduces a pan-European study. The potential roles of nurses and midwives in this area are illustrated by a case report. Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored to prevent anything similar happening again. However, monitoring is incomplete and questions remain unanswered. Many medicines are essential for the health of pregnant women. However, drug use in pregnancy requires surveillance. Methods include spontaneous reporting of adverse events, cohort studies and case control studies. It is hoped that a Europe-wide study, combining data from several congenital anomaly registers, will provide a sufficiently large population to assess the impact of selected drugs on congenital anomalies. However, this work depends on the consistency of reporting by nurses and midwives. Drug safety in pregnancy remains undetermined. Collaboration across Europe has the potential to provide a framework for safety evaluation. Prescribers should consider the possibility of pregnancy in women of child-bearing age. Careful review of maternal drug use in early pregnancy is essential. Midwives and nurses should be aware of adverse event drug reporting systems, including congenital anomaly registers.

Drug safety in pregnancy: Utopia or achievable prospect? Risk information, risk research and advocacy in Teratology Information Services

Even though from preclinical testing to drug risk labeling, the situation with drugs in pregnancy has improved substantially since the thalidomide scandal, there is still an increasing need to provide healthcare professionals and patients with updated individualized risk information for clinical decision making. For the majority of drugs, clinical experience is still insufficient with respect to their safety in pregnancy. There is often uncertainty in how to interpret the available scientific data. Based on 20 years of experience with Teratology Information Services (TIS) cooperating in the European Network of Teratology Information Services (ENTIS) methods of risk interpretation, follow-up of exposed pregnancies through the consultation process and their evaluation is discussed. Vitamin K antagonists, isotretinoin and angiotensin (AT) II-receptor-antagonists are presented as examples of misinterpretation of drug risks and subjects of research based on observational clinical data recorded in TIS. As many TIS are poorly funded, advocacy is necessary by establishing contacts with decision makers in health politics and administration, informing them of the high return in terms of health outcomes and cost savings provided by TIS as reference institutions in clinical teratology.

First experience of the newly established center for drug safety in pregnancy and lactation in St Petersburg, Russia

In any highly contested political domain, language can be a potent force for change or an obstacle to understanding and coalition building across difference. This is surely the case in the global debates over sexuality and gender, where even those terms themselves have aroused heated conflicts. In this spirit, we want to challenge the uncritical use of the term “sexual minorities”, based on a number of historical and conceptual problems with which that term – like the larger thicket of identities and identity politics it signifies – is encumbered. These include: ignoring history, legitimating dubious normativity, fixing biological categories, and recreating exclusions. With this struggle, we seem caught in a modernist dilemma between two desires: to name and honour difference by signifying identities and to avoid exclusivity and hierarchy by reclaiming universals. The insistence of diverse groups on naming themselves and achieving recognition of their distinctness and variety will go on as long as aspirations for democracy exist, because that is the nature and necessity of emancipatory politics. At the same time, our language needs to reflect the fluidity and complexity of sexuality and gender expressions in everyday life and their intricate interweaving with other conditions such as class, race, ethnicity, time and place.Dans tout domaine politique très contesté, le langage peut être une force puissante de changement ou un obstacle à la compréhension et à la création de coalitions dépassant les différences. C'est sûrement le cas dans les débats mondiaux sur la sexualité et le genre, où même ces termes ont suscité des conflits houleux. Dans cet esprit, nous souhaitons remettre en question l'utilisation non critique de l'expression « minorités sexuelles », en nous basant sur les problèmes historiques et conceptuels avec lesquels ce terme, comme l'enchevêtrement d'identités et de politiques identitaires qu'il signifie, est associé. Ignorer l'histoire, légitimer une normativité douteuse, fixer des catégories biologiques et recréer des exclusions figurent au nombre de ces problèmes. Avec cette lutte, nous semblons nous trouver dans un dilemme moderniste pris entre deux désirs : désigner et honorer la différence en signifiant des identités, et éviter l'exclusivité et la hiérarchie en récupérant des normes universelles. L'insistance de divers groupes pour se nommer eux-mêmes et faire reconnaître leur différence se poursuivra aussi longtemps que les aspirations à la démocratie existeront, car telle est la nature et la nécessité des politiques émancipatoires. En même temps, notre langage doit refléter la fluidité et la complexité des expressions de la sexualité et du genre dans la vie quotidienne et leurs liens complexes avec d'autres conditions comme la classe, la race, l'origine ethnique, le temps et le lieu.En toda esfera política muy refutada, el idioma puede ser una fuerza potente para lograr cambios o un obstáculo a la comprensión y al desarrollo de coalición para saldar diferencias. Indudablemente, ese es el caso en los debates mundiales sobre la sexualidad y el género, donde incluso esos mismos términos han suscitado conflictos acalorados. En ese espíritu, queremos cuestionar el uso ciego del término “minorías sexuales”, basándonos en varios problemas históricos y conceptuales de los cuales está cargado ese término, como el matorral más amplio de identidades y política de identidades que significa. Algunos ejemplos son: hacer caso omiso de la historia, legitimar normatividad dudosa, arreglar categorías biológicas y recrear exclusiones. Con esta lucha, parecemos estar atrapados en un dilema modernista entre dos deseos: nombrar y honrar diferencias expresando identidades y evitar la exclusividad y jerarquía reclamando universales. La insistencia de diversos grupos en autonombrarse y lograr el reconocimiento de su particularidad y variedad perdurará siempre que existan aspiraciones de democracia, porque esa es la naturaleza y necesidad de la política emancipadora. A la vez, nuestro idioma debe reflejar la fluidez y complejidad de las expresiones de sexualidad y género en la vida cotidiana, así como su intrincado entrelazado con otras condiciones como clase, raza, etnia, tiempo y lugar.

More questions than answers! Clinical dilemmas in psychopharmacology in pregnancy and lactation.

Women in childbearing age frequently suffer from mental illness. Maternal psychiatric disorders may have a devastating impact on the fetus and the newborn. Thus treating or preventing relapse of these disorders during pregnancy and puerperium is a clinical and ethical duty with the necessity to avoid or minimize fetal or neonatal drug exposure. Though there are many guidelines and comprehensive reviews regarding drug safety in pregnancy and lactation, the application of these recommendations into clinical practice appears to be complex. Hence, we present some clinical questions with answers considering the available literature on safety of psychotropics in pregnancy and lactation.

Pregnancy exposure registries for assessing antimalarial drug safety in pregnancy in malaria-endemic countries.

Because pregnant women are routinely excluded from pre-licensure clinical trials for fear of harming the mother or the developing foetus [1], most drugs are marketed with limited information on their safety during pregnancy and therefore are not recommended for use by pregnant women. Yet drugs are widely used by pregnant women, and medication often cannot be avoided in chronic diseases such as epilepsy and HIV or other acute illness that harm the mother and the unborn child if left untreated.

Advice on Drug Safety in Pregnancy

Safety regarding use in pregnancy is not established for many drugs. Inconsistencies between sources providing drug information can give rise to confusion with possible therapeutic consequences. Therefore, it is important to measure clinically important differences between drug information sources. The objective of this study was to compare two easily accessible Norwegian sources providing advice on drug safety in pregnancy - the product monographs in the Felleskatalog (FK), published by the pharmaceutical companies, and the five regional Drug Information Centres (DICs) in Norway - in addition to assessing the frequency of questions regarding drug safety in pregnancy made to the DICs according to the Anatomical Therapeutic Chemical (ATC) classification system. Advice on drug use in pregnancy provided by the DICs in 2003 and 2005 were compared with advice in the product monographs for the respective drugs in the FK. Comparison of advice was based on categorization to one of four categories: can be used, benefit-risk assessment, should not be used, or no available information. A total of 443 drug advice were categorized. Seven out of ten of drugs frequently enquired about, according to the ATC system, were drugs acting on the nervous system (group N). For 208 (47%) of the drugs, advice differed between the DICs and FK. Advice from the FK was significantly (p < 0.01) more restrictive than advice from the DICs. There were no differences in the level of consistency of advice between drugs that were newly introduced and those that had been on the market for a longer time, advice regarding use of drugs in the first trimester and advice regarding use of drugs in the second or third trimester, or between advice provided during 2003 and during 2005. The results of this study show considerable differences between two Norwegian sources providing advice on the use of drugs in pregnancy. Based on the knowledge that healthcare providers choose sources of information in a random manner, our results may be of clinical importance. We believe that the problem with heterogeneous drug information on this subject is not confined to Norway and that our results should be of international interest.

Treating the mother – protecting the unborn: The safety of hypoglycemic drugs in pregnancy

The purpose of this review is to provide a brief overview of the safety of antidiabetics in pregnancy. Specifically, concerns over teratogenicity due to the possible placental transfer of antidiabetics as well as maternal and neonatal outcomes are addressed. Several new insulin analogs are currently available for the treatment of diabetes. Due to the improved glycemic control demonstrated in non pregnant patients, these analogs may also prove to be beneficial in pregnancy. Insulin lispro is the only insulin analog that has been systematically studied in pregnancy. Results of these studies show a lack of transfer across the placenta and no adverse fetal and neonatal outcomes. The use of oral hypoglycemic agents in pregnancy is also generating interest. To date, there has been only one randomized controlled trial investigating the use of glyburide which found it to be safe and effective in the management of gestational diabetes mellitus. The lack of randomized controlled trials for antidiabetics in pregnancy highlights the need for more comprehensive investigation regarding their safety and efficacy.

Postmarketing surveillance for drug safety in pregnancy: The Organization of Teratology Information Services Project

Although medications are frequently used during pregnancy, premarketing studies exclude pregnant women, with the result that maternal and fetal risks of medications are largely unknown prior to marketing. To demonstrate the feasibility of using Teratology Information Services (TISs) to identify potential subjects who may participate in postmarketing surveillance studies regarding medications taken during pregnancy, maternal characteristics and pregnancy exposure data routinely collected from callers to member agencies of the Organization of Teratology Information Services (OTIS) were pooled for two one-month periods. A total of 3536 calls inquiring about 7746 different agents were received from pregnant women. Of the 40 medications about which pregnant women most frequently asked, the top two were nonprescription acetaminophen and pseudoephedrine, three were prescription drugs with a U.S. Food and Drug Administration pregnancy label category D designation, and five were prescription antidepressants. TISs are well positioned to prospectively ascertain medication exposures in large numbers of pregnant women and may be an exceptional resource for conducting postmarketing surveillance for the safety of medications taken during pregnancy.

Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP)

Objective: Our goal was to review the safety and effectiveness of available antiemetics for treatment of nausea and vomiting of pregnancy. Study Design: We performed a quantitative and qualitative overview of observational controlled studies for drug safety in pregnancy and randomized controlled trials for drug effectiveness for nausea and vomiting in pregnancy. Results: All of the following are safe and effective for treatment of varying degrees of nausea and vomiting in pregnancy: Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine), antihistamine (H1) blockers, and phenothiazines; however, the magnitude of effect, particularly for phenothiazines, is in question and may differ among individual agents. Pyridoxine and vitamin B12are safe and may be effective. Metoclopramide, droperidol, and ondansetron may be effective, but safety data are insufficient to recommend them as first-line agents. Corticosteroids may not be as beneficial as first thought, and there may be a small teratogenic risk. The relative effectiveness of various agents is largely unknown. Conclusion: Many medications, particularly H1-antagonists and phenothiazines, are safe and effective for treatment of varying degrees of NVP. (Am J Obstet Gynecol 2002;186:S256-61.)

Do pregnant women report use of dispensed medications?

Surveillance of drug safety in pregnancy often draws on administrative prescription registries. Noncompliance in the use of prescribed medication may be frequent among pregnant women owing to their fear of fetotoxic side effects. To estimate compliance in the use of prescription drugs dispensed during pregnancy, we compared prescription data from the North Jutland Prescription Database with information on drug use provided by pregnant women to the Danish National Birth Cohort (DNBC), which is a health interview survey. We used the North Jutland Prescription Database to identify all prescription drugs dispensed during pregnancy for the 2,041 women who were enrolled in the DNBC in the County of North Jutland, Denmark. Compliance was defined as the probability of reporting drug use in DNBC after purchasing a dispensed prescription drug. The overall compliance to drugs purchased within 120 days before the interview was 43% (95% confidence interval = 40-46). Drugs used for treating chronic diseases, for example, beta-blockers, insulin, thyroid hormones, and diuretic and antiepileptic drugs, were always reported to be used, but compliance was low for drugs used for local or short-term treatment such as antihistamines, antibiotics, antacids, nonsteroid anti-inflammatory drugs, and gynecologic drugs. Thus, for the latter drug groups the prescription database may provide an incomplete identification of exposure. Neither data source is unbiased regarding actual drug intake. Nevertheless, our results indicate that for some drug groups risk assessment studies based on prescription data may produce false negative results as a result of noncompliance.

Bacterial Isolates from the Urine of Women in Ilorin and their Antibiotic Susceptibility Patterns

Context : Urinary tract infections (UTI) are commonly encountered in women and, often, antibiotics are prescribed before bacteriological results are available. There is therefore a need to determine empirical antibiotics suitable in such situations. Objective : The aims of the study were to identify the pathogens causing UTI in pregnant and non-pregnant women, determine their antimicrobial sensitivity patterns and suggest appropriate empirical antimicrobial agents for use in such patients. Study Design and Setting : A cross-sectional study at the Department of Obstetrics and Gynaecology, University of Ilorin Teaching Hospital, Ilorin, Nigeria. Methods : Urine samples of women suspected to have UTI were sent for microscopy, culture and sensitivity tests. The results were analyzed and the differences between the results of pregnant and non-pregnant patients were assessed, using the chi-square test. Results : Escherichia coli was the predominant cause of UTI in both groups of women. Staphylococcus aureus (0.05>p>0.01), Proteus species (0.05>p>0.01) and Pseudomonas (0.05>p>0.01) were more likely to be isolated in non-pregnant women. Sultamicillin, azithromycin, nitrofurantoin, nalidixic acid, gentamycin and cotrimoxazole demonstrated ‘good' to ‘very good' effectiveness against the organisms. The more recent, expensive antibiotics like ofloxacin, ciprofloxacin, ceftriaxone and cefuroxime demonstrated ‘excellent' effectiveness against the organisms. Antibiotics were generally more effective in clearing UTI in pregnancy. Conclusions and Recommendation : Antibiotics for empirical treatment of UTI in this environment should be those with good to excellent activities as listed above. Consideration should be given to the severity of the infection, drug safety in pregnancy and cost-effectiveness in making the appropriate choice for each patient. (Tropical Journal of Obstetrics and Gynaecology: 2001, 18(2): 61-65)

Assessing the safety of drugs in pregnancy: the role of prospective cohort studies.

Since, for obvious reasons, systematic testing of the teratogenic properties of drugs in humans is not possible in the premarketing phase, the epidemiological approaches to postmarketing risk evaluation are of major importance. Cohort studies, with their prospective exposure assessment, their ability to study even exposure to drugs not commonly used in pregnancy, and their ability to monitor both adverse and beneficial fetal outcomes, seem to be the most promising study type from a methodological viewpoint. Although there are numerous cohort studies on the harmful effects of drug use in pregnant women, only a few have been able to demonstrate a risk in terms of an increase in the prevalence of malformations. Most studies with significant findings were those investigating the risk potential of one group of drugs, the anticonvulsants. The lack of cohort studies showing a risk for drug use in pregnancy, however, is not necessarily indicative of some methodological deficiency. Rather, it may suggest that, for the majority of drugs, their use in pregnancy is not associated with an increased risk of congenital malformations.

Effect of over-the-counter drugs on the unborn child: what is known and how should this influence prescribing?

The developing organism is unique in its responsiveness to drugs. The predictability of therapeutic effectiveness and safety of drugs in pregnancy using the adult as a model for pharmacokinetics and pharmacodynamics can result in grave consequences in the fetus. There exists a general misconception that since over-the-counter (OTC) drugs are readily available, these pharmaceutical agents can be viewed as safe to use by adults. Ingestion of OTC preparations during pregnancy results in placental transfer and accumulation of these drugs in the fetus. As the fetus lacks the ability to handle pharmaceutical agents, since renal function, metabolic pathways, etc. are not fully developed, drug exposure in utero may produce deleterious effects in the fetus but not the mother. Clinicians are aware of drug-induced effects on the fetus and have dramatically reduced the use of prescription drugs during pregnancy. However, the use of self-medication (OTC) has significantly increased during pregnancy through extensive, effective advertising by the pharmaceutical industry and lack of sufficient data indicating an OTC effect on the fetus. However, the consequences of OTC drug use need to be established, since these compounds continue to be used extensively, especially during pregnancy.

Safety of acid-suppressing drugs.

There is an extensive literature on the adverse effects of drugs that inhibit gastric acid secretion. This study presents a critical examination of interactions between antisecretory drugs and other compounds, the frequency of serious adverse effects relating to various body systems, the safety of antisecretory drugs in pregnancy, and longer-term safety data from postmarketing surveillance studies. While interactions with some other drugs, alcohol, and certain carcinogens are of potential concern, in practice clinically significant reactions appear to be rare if they occur at all. A small number of major side-effects have been documented, but they occur rarely, and postmarketing surveillance has not detected other longer-term sequelae. Safety of these drugs in pregnancy is not established, as data are so few. It is concluded that antisecretory agents, by comparison with most other classes of drugs, are remarkably well tolerated.

Book Review: Drug Safety in Pregnancy

Book Review: Drug Safety in Pregnancy

Oral antidiabetic drugs in pregnancy

A recent report casts doubt on the safety of oral antidiabetic drugs in pregnancy by suggesting that chlorpropamide (Diabinese - Pfizer), in high doses is associated with a high perinatal mortality (Brit. med. J. 1963, 1, 59). Out of 19 diabetic mothers who received 500 mg of the drug daily, 14 (74%) had perinatal loss. It is not clear whether this is due to inadequate diabetic control or to some direct effect of the chlorpropamide. Confirmation of these results is desirable and more information about the effects of other antidiabetic sulphonylurea derivatives in pregnancy (for example, tolbutamide) is also needed. There is little evidence that oral antidiabetic drugs induce congenital abnormalities in the human foetus, although cases have been reported (Lancet 1960, 2, 1424; 1961, 1, 891). The British manufacturers of oral antidiabetic drugs warn against their use in pregnancy.