Janine E. Polifka

Evolving knowledge of the teratogenicity of medications in human pregnancy

A majority of pregnant women take at least one medication during pregnancy, although the safety of such drugs during pregnancy is not always known. We reviewed the safety during pregnancy of 172 drugs approved by the US Food and Drug Administration (FDA) from 2000 to 2010 using the TERIS risk rating system. We also reviewed safety information for 468 drugs approved by the FDA from 1980 to 2000 to determine if revisions in risk categories had been made in the last 10 years. The teratogenic risk in human pregnancy was “undetermined” for 168 (97.7%) of drug treatments approved between 2000 and 2010. Furthermore, the amount of data available regarding safety in pregnancy was rated as “none” for 126 (73.3%) of these drugs. For those drugs approved between 1980 and 2000, only 23 (5%) changed a full risk category or more in the past 10 years. Sources of data that led to a revised risk were derived from exposure cohort studies performed through record linkage studies, teratogen information services, large population‐based case‐control studies, and pregnancy registries. The mean time for a treatment initially classified as having an “undetermined” risk to be assigned a more precise risk was 27 years (95% confidence interval 26–28 years). The lack of information needed to assess the safety of drug treatments during human pregnancy remains a serious public health problem. A more active approach to post‐marketing surveillance for teratogenic effects is necessary.

Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases.

In patients with psoriasis, there is an increased availability of drugs for treatment. However, there are important questions about drug safety for mothers with psoriasis and their fetuses. Currently, there are limited safety data for many of the medications used. In this article, we review current pregnancy risk information for medications commonly used in the treatment of psoriasis. In addition, a list of teratology information resources is included to help practicing clinicians find up-to-date information regarding the safety of the medications they prescribe.

Drug safety in pregnant women and their babies: ignorance not bliss.

Although clinical trials address questions regarding drug safety for most segments of the population, pregnant women constitute one special group that is “orphaned” with respect to this issue. The lack of adequate pregnancy safety information for the vast majority of medications, combined with a need to make appropriate treatment decisions and to communicate risk information to a potentially vulnerable population, are some of the most challenging and critical womens health issues.

Reliability and validity of the 4‐item perceived stress scale among pregnant women: Results from the OTIS antidepressants study

We aimed to estimate the reliability of the 4-item Perceived Stress Scale (PSS) and its validity in predicting maternal depression and quality of life (QoL). Data regarding stress, depression and QoL were collected during pregnancy among a sub-sample from the Organization of Teratology Information Specialists Antidepressants in Pregnancy Cohort. The 4-item PSS demonstrated acceptable internal consistency (Cronbachs alpha coefficient = .79), alternate forms stability reliability with the 10-item PSS (Pearson correlation coefficient r = .63; p < .001), convergent validity with the Edinburgh Postnatal Depression Scale (r = .67; p < .001), and concurrent validity with the mental health component of the Short-Form-12 (r = -.62; p < .001) as a measure of QoL. The 4-item PSS is a valid and useful tool for assessing maternal stress during pregnancy.

Clinical teratology: identifying teratogenic risks in humans.

About 10% of congenital anomalies are caused by effects of exogenous factors on the developing embryo or fetus (1). Although this is a relatively small subgroup, it is especially important because these congenital anomalies are potentially preventable. This paper reviews the contribution of exogenous factors to the etiology of human congenital anomalies and discusses our approach to common problems in clinical teratology.

Fetal sex and maternal asthma control in pregnancy

Asthma is a prevalent chronic disorder that might substantially complicate pregnancy. Some recent reports suggest that the presence of a female fetus might be associated with worse maternal asthma symptoms during pregnancy. We tested this hypothesis using the sample of 719 pregnant women with asthma prospectively enrolled in the OTIS study. The presence of a female fetus was associated with a higher incidence of hospitalizations for asthma during pregnancy (OR = 1.84; 95% CI: 1.05; 3.21) independent of maternal age, BMI, ethnicity, smoking, and socioeconomic status. The current study suggests that pregnant asthmatic women carrying a girl might be more susceptible to asthma exacerbations.

Weighing the risks and the benefits : A call for the empirical assessment of perceived teratogenic risk

Pregnant women are often faced with complex decisions about whether to undergo medical treatment or continue working in an occupational setting that is permeated with hazardous chemicals. The task for these women is to weigh the benefits of these activities against the potential risks that they may have on the developing embryo. Scientific uncertainty with respect to the teratogenicity of drugs and chemicals in humans leaves health care professionals and their pregnant patients with little predictive information. Cognitive research has shown that it is difficult for people to make complex decisions, particularly when the risks are uncertain. Although the problems inherent in counseling pregnant women regarding teratogenic risk are not new, little time has been devoted to the empiric assessment of how people perceive teratogenic risk and how teratogenic risk information can be best communicated. This article explores the variables that have been found, through psychometric research, to influence peoples perception of risk and how cognitive models derived from these studies may be applicable to teratogen information counseling. Understanding the variables that shape the perception of teratogenic risk can help health care professionals improve how they communicate these risks to their patients. Improved teratogenic risk communication will result in better management of pregnancies and reduction of costly litigation that ensues when risks are not properly communicated and understood.

Is there an embryopathy associated with first‐trimester exposure to angiotensin‐converting enzyme inhibitors and angiotensin receptor antagonists? A critical review of the evidence

Drugs that interfere with the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), are widely used to manage hypertension and heart failure. Adequate functioning of the RAS is essential for normal fetal kidney development. The potential for ACEIs and ARBs to impair fetal and neonatal renal function if taken after the first trimester of pregnancy has been well documented. Although these drugs were not found to be teratogenic in animals, until recently little was known about the teratogenic effects of ACEIs and ARBs in humans when exposure was limited to the first trimester of pregnancy. New evidence from epidemiologic studies indicates that there may be an elevated teratogenic risk when these drugs are taken during the first trimester of pregnancy. However, this elevated risk does not appear to be specific to ACEIs and ARBs, but is instead related to maternal factors and diseases that typically coexist with hypertension in pregnancy, such as diabetes, advanced maternal age, and obesity. Women who become pregnant while being treated with an ACEI or ARB should be advised to avoid exposure to these drugs during the second and third trimesters of pregnancy by switching to a different class of antihypertensive drugs between weeks 8 and 10 after conception.

Better Data Needed from Pregnancy Registries

This article is a consensus position statement from the Research Committee of the Organization of Teratology Information Specialists (OTIS). The Committee believes that more specific information on the timing and dose of drug exposures from pregnancy birth defect registries sponsored by pharmaceutical companies (herein called pregnancy registries) would improve the estimation of risk for developmental toxicity (i.e., growth alteration, structural anomalies, functional/neurobehavioral deficits, or death). Specifically, the Committee believes that the exposure timing should be stated in gestational weeks and days rather than simply weeks. In addition, the Committee believes that the exposure dose should be stated in patient-specific terms, such as body weight (mg/kg) or body surface area (mg/m(2)) rather than simply dose strength. Although the focus of this position is pregnancy registries, it also is applicable to any source of medication-induced embryo-fetal toxicity.

Should pregnant women be included in phase IV clinical drug trials

Relatively few drugs, especially those recently approved by the US Food and Drug Administration, have published human pregnancy experience. Although all drugs contain animal reproduction data, these are usually not predictive of human risk. Clinical trials in pregnant women are rarely conducted because of ethical and legal concerns, and it may be many years before sufficient observational data are collected to guide clinical treatment decisions. Because many of these drugs will be used in pregnancy, human data are needed shortly after the drugs come to the market. Lack of human data leads to uncertainty over whether a drug can be safely prescribed for a pregnant patient. Unless there are compelling scientific and ethical reasons to exclude them, pregnant women should be included in phase IV clinical trials (postmarketing studies to obtain additional information, including the risks, benefits, and optimal use of a drug). This paper examines how physicians currently counsel pregnant women when there are no human data and proposes an alternative method in which knowledge regarding risks associated with the use of drugs during pregnancy can be enhanced in a clinical trial setting.