Pregnancy Exposure Registries Research Articles

New changes in pregnancy and lactation labelling: Review of dermatologic drugs.

BackgroundThe U.S. Food and Drug Administration has published new pregnancy and lactation labelling rules that set standards on the presentation of information with regard to drug usage during pregnancy and breastfeeding, as well as the effects on fertility. These guidelines became effective June 30, 2015, and classified the risks of using prescription drugs during pregnancy in three detailed subsections: Pregnancy, Lactation, and Females and Males of Reproductive Potential. These sections describe the risks within a real-world context of caring for these patients.ObjectiveIn this study, we reclassified and categorized drugs and treatments commonly used in dermatology according to these new guidelines.MethodsWe performed a search of the medical literature about the use of relevant prescription drugs during pregnancy and breastfeeding and their effect on fertility. The search included prospective and retrospective studies, review articles from PubMed-indexed journals (from inception to November 2018), U.S. Food and Drug Administration records, pregnancy exposure registries, relevant information and studies provided in drug labeling by companies, and updated pharmacologic texts and guidelines up to 2018.ResultsTopical immunomodulators, systemic immunomodulators (including biologics), systemic antipruritic agents, antimicrobials, as well as acne, hair, and cosmetic agents were included. We have made best attempts to review and consolidate existing and new data and include them in our guide.ConclusionThis new narrative format facilitates prescribing by considering a variety of factors. One previously overlooked aspect was the impact on the reproductive potential of both male and female patients. Rather than depending on overly simplistic letter risk categories, dermatologists will now need to make prescribing decisions based on each patient and the information provided, which will allow for better decision making and patient care.

Why South Africa urgently needs to support the development of pregnancy exposure registries

Why South Africa urgently needs to support the development of pregnancy exposure registries

Clinical considerations for the management of psoriasis in women.

The burden of psoriasis is particularly high for women, who report lower levels of happiness (women: 18.5%; men: 11.3% lower vs. general population) and are more likely to experience stress (women: > 60%; men: 42%), loneliness (women: 25-28%; men: 19-24%), stigmatization (Feelings of Stigmatization Questionnaire score; women: 93.2; men: 78.0), and reduced sexual activity (women: 33%; men: 19%) compared with men. The onset of psoriasis is bimodal, with one incidence peak (15-30 years) that coincides with the prime reproductive age for women, which poses specific challenges for their treatment. However, well-established guidelines for the treatment of women of childbearing age are lacking. Many women experience stabilization (21%) or improvement (55%) of their skin during pregnancy, but up to a quarter can experience disease worsening, and postpartum flares are common (> 50%). Therefore, balancing the risk of treatment with the risk of uncontrolled disease is important. Because half of pregnancies are unplanned, the implications of therapeutic options must be considered for all women with psoriasis who are sexually active, irrespective of intentions to start a family. Timely initiation of these discussions by health care professionals is paramount to prevent unintentional toxicity to the developing fetus. For example, acitretin, methotrexate, and oral psoralen/ultraviolet A are all contraindicated in pregnancy. Reassuringly, safety data for other psoriasis treatments during pregnancy are increasingly available, particularly for anti-tumor necrosis factor therapies. Despite encouraging data from pregnancy exposure registries and clinical studies now being included in anti-tumor necrosis factor drug labels, comfort with prescribing these therapies to pregnant women remains low (U.S. dermatologists: 21%; EU-5 dermatologists: 10%). In this article, we review issues specific to treating women of childbearing age with psoriasis and highlight the need for treatment guidelines to ensure consistent care and optimal outcomes for these patients.

Results From the Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study

Results From the Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study

Use of existing electronic health care databases to evaluate medication safety in pregnancy: Triptan exposure in pregnancy as a case study.

PurposeThe recent expansion of electronic health and medical record systems may present an opportunity to generate robust post‐approval safety data and obviate the limitations of prospective pregnancy exposure registries. We examined and compared, over the same time frame, the outcomes of triptan exposure in pregnancy using (1) a retrospective claims database and (2) a previously completed pregnancy registry.MethodsUsing the Marketscan database, the risk of major birth defects was ascertained in live‐born infants whose birth mothers were exposed to sumatriptan, naratriptan, or sumatriptan/naproxen during pregnancy. The frequencies of outcomes observed were compared with the findings of the 16‐year sumatriptan, naratripan, and sumatriptan/naproxen prospective pregnancy registry.ResultsAbout 5120 pregnancies were identified in the retrospective claims cohort in contrast to 617 included in the prospective registry during the same time frame. The proportion of major birth defects among first‐semester sumatriptan exposures was 4.0%, which is exactly the same as the proportion of major birth defects reported for first‐semester sumatriptan exposures in the registry. There were very few non‐livebirth outcomes in both the claims analyses and registry.ConclusionsThese results confirm broad agreement between the database analysis and the registry regarding the safety of triptans during pregnancy. Of note, the number of triptan‐exposed pregnancies identified in this large US database was about 7‐fold that included in the prospective registry over the same time frame. The findings of this study support an approach of using existing health care database (s) in the post‐approval assessment of medication exposure in pregnancy.

WED 190 Teriflunomide pregnancy registry: design and enrolment

IntroductionTeriflunomide is contraindicated in pregnancy, based on developmental toxicity in rats and rabbits. During clinical development, despite requirements for contraceptive use, some pregnancies occurred. There were no signs of structural or functional deficits in newborns.MethodsThe multinational, prospective, observational International Teriflunomide Pregnancy Exposure Registry is enrolling teriflunomide-exposed pregnant women with MS. Signed informed consent is obtained prior to enrolment. In the UK, healthcare professionals submit information to the National Coordinating Centre (Manchester, UK). Infants are followed until 1 year old. Pregnancy outcomes, including birth defects and infant characteristics, are collected. Target recruitment: 196 women to achieve 104 live births, providing 80% power to detect 3.95-fold increase in risk of birth defects associated with teriflunomide exposure vs the European Surveillance of Congenital Anomalies (EUROCAT) network.ResultsAs of 26/04/2017, 14 patients have been recruited from 7 European countries (none in the UK). Six healthy babies have been born to date. One patient had an elective termination not motivated by abnormal prenatal test results or concerns regarding potential birth defects.ConclusionThis registry aims to provide data on pregnancy outcomes and infant development from teriflunomide-exposed women, which may help physicians provide better patient advice.Study supported by Sanofi.

Suggestion for Guidelines of Pregnancy Exposure Registry

Suggestion for Guidelines of Pregnancy Exposure Registry

Assessing the value of Western Cape Provincial Government health administrative data and electronic pharmacy records in ascertaining medicine use during pregnancy.

In African settings, where there is a high disease burden, there is a need to improve the science of documenting and analysing accurate information regarding medicine exposures in women immediately before and during pregnancy to assess the extent of use and safety in pregnant women and their unborn children. To compare evidence of medicine use during pregnancy, as documented in paper-based clinical records (maternity case records (MCRs)) against electronic health information resources (Provincial Health Data Centre (PHDC)) and assess the level of concordance between the two as part of baseline investigations before piloting a provincial pregnancy exposure registry and birth defect surveillance system. The PHDC consolidates electronic clinical and pharmacy data. A folder review of completed pregnancies between November 2013 and January 2016 was conducted on randomly selected MCRs from midwife-run obstetric units and a secondary maternity hospital in Cape Town, South Africa. Medication exposures in the MCR were captured and compared with a customised PHDC data extract. The type and timing of drug exposures were compared. Total exposures were compiled from all data sources. Two hundred and six MCRs from three facilities were sampled: 83 women had documented antiretroviral therapy (ART) exposure; all but 1 (1%) had been recorded in the PHDC extract. There was no evidence of ART use in the MCRs of 4 (5%) cases, despite evidence in the PHDC. There were imprecise drug names in the MCRs of 14 (17%) ART patients, discordant dates of onset between the MCRs and PHDC extracts in 10/83 (12%) and inaccurate medicine names and incorrect dates in 1 (1%) case each. Nine of 10 (90%) women who were administered antituberculosis medication were recorded in the PHDC extract. Ten of 21 (48%) isoniazid preventive therapy treatments appeared in the MCRs and PHDC; 9 (42%) in the PHDC only and 2 (10%) in the MCRs only. Half (n=18/36) of all antibiotic use was reflected only in the MCRs, while 13/36 (36%) appeared only in the PHDC extract. In the former cases, antibiotics used for treatment of sexually transmitted infections and urinary tract infections were dispensed from ward stock and not captured electronically. Antibiotics reflected only in the PHDC were either dispensed at a referral facility or before the first recorded antenatal clinic visit. Folic acid and iron were mostly documented in the MCR only (n=79/99 (80%) and n=107/128 (84%), respectively). However, analgesics and antihistamines more often appeared in the PHDC extract only (n=11/16 (73%) and n=5/5 (100%), respectively). The PHDC extract provided a better and more complete reflection of chronic drug exposures compared with the MCRs, especially when women sought care at facilities other than the antenatal care unit where they first attended, or when exposures occurred before the initial antenatal visit. The exception was antibiotics dispensed from ward stock to treat sexually transmitted and urinary tract infections.

Utilization of drugs with pregnancy exposure registries during pregnancy

To describe the utilization of drugs with pregnancy exposure registries by trimester during pregnancy, in comparison with matched nonpregnant episodes and a pre-pregnancy period. We identified live-born deliveries from women aged 10 to 54years and matched the pregnancies 1:1 with nonpregnant episodes from a comparator cohort not delivering live-born infants, using data from 2001 to 2013 in the Sentinel Distributed Database. We evaluated the utilization of 34 drugs with pregnancy exposure registries, comparing utilization during pregnancy to the matched nonpregnant episodes, and to the 90days before pregnancy. We identified 1895597 pregnancies ending in live births in 1598697 women and 1895597 matched nonpregnant episodes in 1582581 women. We observed a lower prevalence of use for most drugs during pregnancy compared with the matched nonpregnant episodes, and the 90-day pre-pregnancy period. The median (interquartile range) prevalence ratio of use, at any time during pregnancy, for all products was 0.2 (0.1-0.3) comparing pregnant to nonpregnant episodes. Overall, there was a decrease in drug utilization by trimester; from 2.6% in the 90days preceding pregnancy to 2.1% in the first trimester, 1.1% in the second trimester, and 0.9% in the third trimester. Among drugs with pregnancy exposure registries, use was less during pregnancy compared with before pregnancy and to the matched nonpregnant episodes. The lower utilization during pregnancy suggests that women may be avoiding these drugs to minimize potentially harmful exposure during pregnancy. This lower utilization may increase the challenges of further studying the safety of these drugs using pregnancy exposure registries.

Implementation of a prospective pregnancy registry for antiretroviral based HIV prevention trials

Background: Safety data on pregnancy and fetal outcomes among women in HIV prevention trials are urgently needed to inform use of effective antiretroviral agents for HIV prevention. We describe an effective, efficient, and novel method to prospectively collect perinatal safety data concurrent with on-going parent clinical trials.Methods: The Microbicide Trials Network (MTN)-016 study is a multinational prospective pregnancy exposure registry designed to capture pregnancy and neonatal outcomes. Studies currently contributing data to this registry included phase I and II safety trials with planned exposures to candidate HIV prevention agents, as well as phase IIB and III efficacy trials capturing data on pregnancy and infant outcomes following inadvertent fetal exposure during study participation.Results: To date, participants from two phase I studies and two effectiveness trials have participated in MTN-016, resulting in 420 pregnant women and 381 infants enrolled. Infant retention has been high, with 329 of 381 (86%) infants completing the 12-month follow-up visit.Conclusion: In a research setting context, it is feasible to establish and implement a prospective, multinational HIV chemoprophylaxis pregnancy registry that will generate pregnancy exposure data in a robust fashion.

Discovering Cohorts of Pregnant Women From Social Media for Safety Surveillance and Analysis.

BackgroundPregnancy exposure registries are the primary sources of information about the safety of maternal usage of medications during pregnancy. Such registries enroll pregnant women in a voluntary fashion early on in pregnancy and follow them until the end of pregnancy or longer to systematically collect information regarding specific pregnancy outcomes. Although the model of pregnancy registries has distinct advantages over other study designs, they are faced with numerous challenges and limitations such as low enrollment rate, high cost, and selection bias.ObjectiveThe primary objectives of this study were to systematically assess whether social media (Twitter) can be used to discover cohorts of pregnant women and to develop and deploy a natural language processing and machine learning pipeline for the automatic collection of cohort information. In addition, we also attempted to ascertain, in a preliminary fashion, what types of longitudinal information may potentially be mined from the collected cohort information.MethodsOur discovery of pregnant women relies on detecting pregnancy-indicating tweets (PITs), which are statements posted by pregnant women regarding their pregnancies. We used a set of 14 patterns to first detect potential PITs. We manually annotated a sample of 14,156 of the retrieved user posts to distinguish real PITs from false positives and trained a supervised classification system to detect real PITs. We optimized the classification system via cross validation, with features and settings targeted toward optimizing precision for the positive class. For users identified to be posting real PITs via automatic classification, our pipeline collected all their available past and future posts from which other information (eg, medication usage and fetal outcomes) may be mined.ResultsOur rule-based PIT detection approach retrieved over 200,000 posts over a period of 18 months. Manual annotation agreement for three annotators was very high at kappa (κ)=.79. On a blind test set, the implemented classifier obtained an overall F1 score of 0.84 (0.88 for the pregnancy class and 0.68 for the nonpregnancy class). Precision for the pregnancy class was 0.93, and recall was 0.84. Feature analysis showed that the combination of dense and sparse vectors for classification achieved optimal performance. Employing the trained classifier resulted in the identification of 71,954 users from the collected posts. Over 250 million posts were retrieved for these users, which provided a multitude of longitudinal information about them.ConclusionsSocial media sources such as Twitter can be used to identify large cohorts of pregnant women and to gather longitudinal information via automated processing of their postings. Considering the many drawbacks and limitations of pregnancy registries, social media mining may provide beneficial complementary information. Although the cohort sizes identified over social media are large, future research will have to assess the completeness of the information available through them.

Results on exposure during pregnancy from a pregnancy registry for AS04-HPV-16/18 vaccine.

To assess pregnancy outcomes after exposure to AS04-HPV-16/18 vaccine (Cervarix, GSK, Belgium) prior to, or during pregnancy, as reported to a pregnancy registry. A pregnancy exposure registry was established to collect data in the United Kingdom and the United States. Exposure was defined as vaccination with AS04-HPV-16/18 within 60days before the estimated conception date and delivery. Reporting was voluntary. Between September 2007 and November 2015, 306 pregnancy exposure reports were received of which 181 were prospective, evaluable reports. From these 181 reports, 154 (85.1%) pregnancies resulted in a live birth, 14 (7.7%) in spontaneous abortion, one (0.5%) in stillbirth, and 12 (6.6%) were electively terminated. There was no clustering of outcomes with respect to the timing of exposure. There were 18 infants born with a congenital anomaly of which nine were minor structural defects, seven were major structural defects, one was a hereditary disorder and one was likely the result of a congenital infection. In three cases of structural defect (two minor and one major), there was a temporal association to vaccination during the critical developmental period of gestation. There was no cluster or constellation of congenital anomalies suggestive of possible teratogenesis. The pharmacovigilance plan to investigate the effects of inadvertent exposure to AS04-HPV-16/18 vaccine during pregnancy included assessment of pregnancy outcomes among women enrolled in clinical trials, evaluation of pregnancy exposure reports from all countries as part of routine passive safety surveillance, a large, well conducted post-authorization observational study, and the pregnancy registry. These registry data complement other data from clinical trials and post-marketing surveillance showing no evidence that vaccination with AS04-HPV-16/18 during the defined exposure period (within 60days before conception until delivery) increases the risk of teratogenicity.

Safety assessment of herbal drugs in pregnancy

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation.

Evaluating the Safety of Medication Exposures During Pregnancy: A Case Study of Study Designs and Data Sources in Multiple Sclerosis.

BackgroundRegulatory agencies often request prospective, product-specific post-authorization pregnancy exposure registries to monitor safety during pregnancy, even though studies using existing health databases could also be employed.ObjectivesUsing multiple sclerosis (MS) as a case study, we evaluated various study designs and data sources previously used to study medication exposure in pregnancy.MethodsWe examined (1) strengths and limitations of study designs used for pregnancy safety studies in women exposed to MS-specific medications during pregnancy and (2) existing data sources used to conduct such studies in other disease areas. For the data sources identified, we contacted data custodians to determine the feasibility of assessing the risk of adverse outcomes in women with MS exposed to disease-modifying therapies (DMTs) during pregnancy.ResultsOf 43 MS-specific studies identified, most of which were prospective registries, very few, regardless of design and study population, produced timely and robust results for spontaneous abortions and major congenital malformations, considering study duration, achievement of target enrollment numbers, inclusion of internal comparators, and publication of results. Building on the successful use of existing healthcare databases to investigate drug safety during pregnancy in other disease areas, we identified 13 data sources that could be used to study intravenous DMT exposures in women with MS.ConclusionsProspective, treatment-specific registries have generally failed to deliver robust information. For this reason, other study approaches, in particular cohort studies using existing healthcare databases, should be considered for evaluating the safety of drug exposure in pregnancy, including in MS.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-017-0114-9) contains supplementary material, which is available to authorized users.

The Safety of Medications in Pregnant Women: An Opportunity to Use Database Studies.

* Abbreviations: FDA — : Food and Drug Administration NAAEDR — : North American Antiepileptic Drug Registry Information on the safety of medications that pregnant women may need is key to protecting the health of the woman and her fetus. When new drugs are first marketed, this information is scarce, because pregnant women are generally excluded from randomized clinical trials. Broader inclusion of pregnant women in clinical research is being discussed by regulatory authorities and funders.1 But even with greater inclusion of pregnant women in clinical trials, safety data from those trials would be limited by the combination of study size, low frequency of many key outcomes, and strict conditions for enrollment. Postapproval observational studies still would be needed to assess drug safety in routine health care. These assessments can be conducted as pregnancy exposure registries or by using existing health databases. Currently, because of our overreliance on pregnancy exposure registries and underuse of database studies, we are missing an opportunity to provide information that would help women and their physicians make better informed decisions about treatment in pregnancy. Pregnancy exposure registries, usually sponsored by a single pharmaceutical company, are a primary method requested by the US Food and Drug Administration (FDA) for postapproval safety studies in pregnant women.2 However, these registries often fail to enroll a sufficient number of exposed pregnancies, and when they do, it is often difficult to interpret results because they generally do not include an internal comparison cohort and rely on comparisons to external data sources, such as the Metropolitan Atlanta Congenital Defects Program.2 The pregnancy registries that have been most successful in enrolling … Address correspondence to Andrea V. Margulis, MD, ScD, RTI Health Solutions, Diagonal 605, 9-1, 08028 Barcelona, Spain. E-mail: amargulis{at}rti.org

A systematic review of pregnancy exposure registries: examination of protocol-specified pregnancy outcomes, target sample size, and comparator selection.

Our study sought to systematically evaluate protocol-specified study methodology in prospective pregnancy exposure registries including pre-specified pregnancy outcomes, power calculations for sample size, and comparator group selection. U.S. pregnancy exposure registries designed to evaluate safety of drugs or biologics were identified from www.clinicaltrials.gov, the FDA's Office of Women's Health website, and the FDA's list of postmarketing studies. Protocols or similar documentation were obtained. We identified 35 U.S. registries for drugs or biologic use during pregnancy. All registries assessed risk for overall major congenital malformations. Pre-specified target enrollment was stated for 18 (51%) registries, and ranged from 150 to 500 exposed pregnancies (median 300). Thirty-two (91%) registries identified at least one comparison group, but only nine (26%) planned to use an internal comparator. The most common external comparator group (n = 24, 69%) was the Metropolitan Atlanta Congenital Defects Program (MACDP). No registries were designed to have sufficient power to assess specific malformations, despite the plausibility that most teratogens cause specific defects. Only half of the registries included a power analysis. Despite their common use, external comparators, including MACDP, have important limitations. In the absence of randomized controlled trial data in pregnant women, pregnancy registries remain an important tool as part of a comprehensive pregnancy surveillance program; however, pregnancy registries alone may not be sufficient to obtain adequate data regarding risks of specific malformations. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of pregnancy outcomes from the Tysabri® (natalizumab) pregnancy exposure registry: a global, observational, follow-up study.

BackgroundPatients with multiple sclerosis (MS) or Crohn’s disease (CD) being treated with natalizumab (Tysabri®, Biogen) who are planning to become pregnant or discover they are pregnant after exposure to natalizumab are currently advised to balance the potential benefits and potential risks of exposure when considering treatment options. This study was undertaken to evaluate pregnancy outcomes of women with MS or CD who were exposed to natalizumab at any time within 3 months prior to conception or during pregnancy. A pregnancy registry was created to better understand the effect of natalizumab exposure on pregnancy outcomes.MethodsThe Tysabri Pregnancy Exposure Registry was a global, observational exposure registration and follow-up study. Evaluations included spontaneous abortions (<22 weeks gestational age), fetal losses (≥22 weeks gestational age), ectopic pregnancies, elective or therapeutic terminations, stillbirths, birth defects, and live births. Birth defects were reviewed and coded in accordance with the Metropolitan Atlanta Congenital Defects Program (MACDP) classification of birth defects.ResultsA total of 369 patients with MS and 7 patients with CD were enrolled prospectively, of whom 355 patients (99.4 %; 349 MS and 6 CD) had known pregnancy outcomes (including 8 twin sets). The spontaneous abortion rate was 9.0 % (n = 32; 95 % confidence interval [C. I.], 6.3–12.5 %). An independent advisory committee review determined the major birth defect rate to be 5.05 % (16 of 316 live births + 1 elective abortion; 95 % C. I., 2.9–8.1 %). The mean gestational age of the live-born infants was 38.3 weeks, and the mean birth weight was 3158.3 g.ConclusionsAlthough the overall rate of birth defects was higher than that observed by the MACDP, these registry outcomes showed no specific pattern of malformations that would suggest a drug effect, and the spontaneous abortion rate was consistent with that of the general population.Trial registrationClinicalTrials.gov NCT00472992 (11 May 2007).

Birth defects and neonatal morbidity caused by teratogen exposure after the embryonic period.

Pharmaceutical pregnancy exposure registries seek to evaluate temporal associations between drug exposures and adverse outcomes, particularly congenital anomalies. These registries record observed associations that may or may not be causally-related to the exposure. Most major congenital malformations (i.e., structural birth defects) result from abnormal development during embryogenesis. A standardized catalog of defects of concern (colloquially the "BPA Codes") is used both in public health surveillance programs and pregnancy exposure registries. There are, however, some anomalies that cause significant morbidity and mortality for which isolated second or third trimester exposures may be pathogenically significant. There currently exists no standardized list of defects for which exposure limited to the fetal period may be problematic. The six-digit-code list was used to determine anomalies that might result from medication exposures limited to the fetal period. Defects with documented first trimester pathogenesis (e.g., anencephaly, heterotaxy) were eliminated from consideration, as were chromosomal and single gene disorders (e.g., trisomy 21, achondroplasia). The remaining defects include the following: (1) those that are known to or could reasonably originate or manifest after the embryonic period (e.g., porencephaly, cataracts); (2) those for which pathogenesis is unclear or variable enough that exposure at any gestational age might be considered relevant (e.g., club foot, microcephaly); and (3) those that include some component of abnormal growth (e.g., hemihyperplasia). "Unspecified" defects (e.g., "abnormality of the leg") were included by default because there is insufficient information to assume first trimester embryogenesis. The final result is a list of major and minor anomalies in 11 organ system categories that may be caused by teratogen exposure during the fetal period. Birth Defects Research (Part A) 106:935-939, 2016. © 2016 Wiley Periodicals, Inc.

New prescription drug labeling for pregnant or nursing women

New prescription drug labeling for pregnant or nursing women

Drug safety: Pregnancy rating classifications and controversies

This contribution consolidates data on international pregnancy rating classifications, including the former US Food and Drug Administration (FDA), Swedish, and Australian classification systems, as well as the evidence-based medicine system, and discusses discrepancies among them. It reviews the new Pregnancy and Lactation Labeling Rule (PLLR) that replaced the former FDA labeling system with narrative-based labeling requirements. PLLR emphasizes on human data and highlights pregnancy exposure registry information. In this context, the review discusses important data on the safety of most medications used in the management of skin disease in pregnancy. There are also discussions of controversies relevant to the safety of certain dermatologic medications during gestation.