Journal of Midwifery & Women’s Health www.jmwh.

org
Review

Medication Safety During Pregnancy: Improving

Evidence-Based Practice
CEU
Susan M. Sinclair, PhD, MPH, Richard K. Miller, PhD, Christina Chambers, PhD, MPH,
Elizabeth M Cooper, CNM, EdD

Nearly 90% of women in the United States have taken medications during pregnancy. Medication exposures during pregnancy can result in adverse
pregnancy and neonatal outcomes including birth defects, fetal loss, intrauterine growth restriction, prematurity, and longer-term neurodevel-
opmental outcomes. Advising pregnant women about the safety of medication use during pregnancy is complicated by a lack of data necessary
to engage the woman in an informed discussion. Routinely, health care providers turn to the package insert, yet this information can be incom-
plete and can be based entirely on animal studies. Often, adequate safety data are not available. In a busy clinical setting, health care providers
need to be able to quickly locate the most up-to-date information in order to counsel pregnant women concerned about medication exposure.
Deciding where to locate the best available information is difficult, particularly when the needed information does not exist. Pregnancy registries
are initiated to obtain more data about the safety of specific medication exposures during pregnancy; however, these studies are slow to produce
meaningful information, and when they do, the information may not be readily available in a published form. Health care providers have valuable
data in their everyday practice that can expand the knowledge base about medication safety during pregnancy. This review aims to discuss the
limitations of the package insert regarding medication safety during pregnancy, highlight additional resources available to health care providers to
inform practice, and communicate the importance of pregnancy registries for expanding knowledge about medication safety during pregnancy.
J Midwifery Womens Health 2016;61:52–67  c 2016 by the American College of Nurse-Midwives.

Keywords: pregnancy, fetus, drug effects, prescription drugs, teratogenesis, patient safety, evidence-based health care

INTRODUCTION ing pregnancy, reviews additional resources available to health

Nearly 90% of women in the United States have taken one or care providers to inform practice, and describes pregnancy
more medications during pregnancy and 70% during the first registries in order to communicate the importance of health
trimester.1 During the past 30 years, first trimester use of pre- care provider participation in pregnancy registries.
scription medications increased by more than 60%1 and use
of 4 or more medications during pregnancy tripled during BACKGROUND
this time, reaching nearly 30% in 2008.1 The use of medica-
tions that have a suspected or known teratogenic or fetotoxic Approximately 51% of pregnancies were unintended in 2008
risk is common. In a systematic review, Daw et al described in the United States.10 The high prevalence of unintended
7 studies from Europe, the United States, and Canada report- pregnancies increases the opportunity for unintentional med-
ing rates for the use for prescription medications considered ication exposure before a woman realizes that she is preg-
to have potential for harm in pregnancy.2 These rates varied nant, at which time she can be well into the first trimester.11,12
widely and generally ranged from 1% to 21%.3–9 A study of Yet, unintentional exposures to medications that are expressly
prescriptions issued in France found that more than 50% of contraindicated in pregnancy inevitably occur, despite public
pregnant women receive a prescription for a medication that awareness of the thalidomide disaster in the 1960s.13 Unfortu-
has a known or suspected fetal risk.5 nately, even medications requiring informed consent from the
To guide treatment decisions and counsel clients, health pregnant woman and monitoring in specific pregnancy pre-
care providers must to be able to quickly locate the best avail- vention programs such as iPLEDGE for isotretinoin Accutane
able information about the safety of a particular medication (Roche Pharmaceuticals, Nutley NJ) and S.T.E.P.S. for thalido-
for the pregnant woman and her developing fetus and use this mide can be inadvertently prescribed during pregnancy.14,15
information to discuss the known risks and benefits with her. Intentional medication use during pregnancy occurs for
Although heath care providers routinely rely on information a variety of reasons. Women may take medications for preex-
provided by the manufacturer, such as the package insert, this isting conditions requiring treatment during pregnancy (eg,
information is significantly limited regardless of whether it is epilepsy, asthma, hypertension) or acute conditions that de-
based on human evidence or animal studies. Often, adequate velop during pregnancy (eg, gestational diabetes, upper res-
safety data are not available. This article discusses the limi- piratory infections, migraines). Women can also intentionally
tations of the package insert regarding medication safety dur- take medications during pregnancy to protect the health of
the fetus, such as antiretroviral treatment to reduce mother-
to-child transmission of HIV.
Address correspondence to Susan Sinclair, PhD, MPH, Associate Profes- A survey of 5381 women who gave birth in the United
sor and Epidemiologist, Clinical Research Program, College of Health and
States between 2006 and 2009 found the most commonly used
Human Services, University of North Carolina Wilmington, 601 South
College Road, Wilmington, NC 28403-5995. E-mail: sinclairs@uncw.edu prescription medications during pregnancy were progestins

52 1526-9523/09/$36.00 doi:10.1111/jmwh.12358 
c 2016 by the American College of Nurse-Midwives
 ✦ Information about the safety of medications during pregnancy is limited, and reliance on the package insert alone is
inadequate.
✦ In a busy clinical setting, health care providers need quick access to high-quality, reliable information about medication
safety during pregnancy.
✦ Health care providers can contribute client data to pregnancy registries to help build the collective information about
medication safety in pregnancy that is needed.

from oral contraceptives, amoxicillin (Amoxil), progesterone, more a legal document on behalf of the manufacturer rather
albuterol (Proventil), promethazine (Phenergan), and estro- than a useful clinical tool. Although the prescribing informa-
genic compounds.16 The most commonly used over-the-coun tion is updated regularly, it generally does not contain all of
ter medication components reported were acetaminophen the information available about the safety of the product, nor
(Tylenol), ibuprofen (Advil), docusate (Dulcolax), pseu- does it routinely include results of studies found in the peer-
doephedrine (Sudafed), aspirin, and naproxen (Aleve). reviewed scientific literature.
Included in this survey was an expert review panel that evalu-
ated safety data for the 54 most commonly used medications.
Food and Drug Administration Pregnancy Categories
Only 2 were determined to have sufficient evidence to assess
teratogenic risk.16 Within the package insert, is the assigned FDA Pregnancy
Category for each medication. Health care providers routinely
rely upon these categories as a simple, convenient measure
The Drug Development Process
of medication risk during pregnancy; however, the categori-
The vast majority of newly approved medications lack ade- cal designations are not as evidence-based or clearly defined
quate human pregnancy data to determine teratogenic risk. as one would hope. For example, one of 5 FDA pregnancy
In a study of 172 new medications approved by the Food and categories (A, B, C, D, and X) are assigned by the manufac-
Drug Administration (FDA) from 2000 to 2010, Adam et al17 turer and approved by the FDA at the time of drug approval
estimated that the teratogenic risk in human pregnancy was (Table 1).21 The alphabetical order of those categories sug-
undetermined for 168 (97.7%) of the new medications. For gest that medication safety during pregnancy is progressively
126 (73.3%) of the new medications, no data were available worse from A to X; however, a careful review of the defi-
regarding safety in pregnancy. nitions reveals that this assumption is incorrect. Categories
Pregnant women are typically excluded from clinical trials C, D, and X are structured differently from A and B; these
for new drug development. Therefore, most medications com- categories weigh risk against benefit and the quantity and
monly used in pregnancy are lacking sufficient data to char- quality of the relevant data and are not progressively riskier
acterize human fetal risk,16,18 which can explain in part why (Table 1).21,22 FDA Category X designation does not neces-
so few new medications designed specifically to treat preg- sarily mean the drug is a known teratogen; rather it increases
nancy complications have been developed or approved.18 In- the weight of the risk in the balance of risk relative to the ben-
frequent reports of pregnancies that inadvertently occurred efit. Another limitation of this system is that the pregnancy
during clinical trials provide some information but are usually categories do not always distinguish between risks based on
too few in number to draw conclusions.19 Biopharmaceutical human data versus risks based on animal data or between dif-
companies and regulators rely largely on animal studies, with ferences in frequency, severity, type of developmental toxici-
extrapolation to humans, when developing the drug’s package ties, and risks that are limited to specific gestational windows
insert. More data in the form of human pregnancy exposures of exposure. Reliance on the pregnancy categories can result
and outcomes are needed to characterize risks and benefits. in poorly informed clinical decision making and could lead
Pregnancy registries and similar noninterventional, observa- to unnecessary induced abortion for potential embryonic or
tional studies are among the tools available to collect more fetal harm based on fear of developmental abnormalities that
data about medication safety during pregnancy. are not likely to be present.23–25
In 2014, a new regulation was approved in the United
Package Insert States that eliminates the 5 FDA pregnancy categories.26 The
intent of the new rule is to establish a consistent format for
In a busy clinical setting, health care providers need to have providing information about the effects of a drug in preg-
quick access to high-quality, reliable information about nancy and lactation and to make the content more compre-
medication safety during pregnancy, and many rely upon the hensive, current, and useful for decision making by women
Physician’s Desk Reference, which houses the package insert and their health care providers.26 Implementation of this
(also referred to as the product prescribing information) regulation was scheduled to begin in June of 2015. Newly
provided by the manufacturer.20 In the United States, every submitted products will require the new label format upon
prescription medication is required to have FDA-approved submission, and the new format will be phased in over a 5-year
prescribing information, which in the current form is much period for all pending submissions and for existing products

Journal of Midwifery & Women’s Health r www.jmwh.org 53

 Table 1. Food and Drug Administration Pregnancy Categories21
Pregnancy Category A Controlled studies show no risk to pregnancy. Adequate, well-controlled studies in pregnant women failed to
demonstrate risk to the fetus.
Pregnancy Category B No evidence of risk in humans. Applies if animal studies show increased risk, but human studies do not; or, if
adequate human studies have not been conducted, animal findings are negative.
Pregnancy Category C Risk cannot be ruled out: Human studies are lacking in availability, and animal studies are either positive for
fetal risk or lacking. In some situations, potential benefits may justify the potential risk.
Pregnancy Category D Positive evidence of risk: Investigational or postmarketing data show risk to the fetus. In some situations,
potential benefits may outweigh the potential risk.
Pregnancy Category X Drug is contraindicated in pregnancy: Studies in animals or humans, or investigational or postmarketing
reports, have shown fetal risk, which clearly outweighs any possible benefit to the patient.

Source: U.S. DHHS. Food and Drug Administration (FDA). Code of Federal Regulations, 21CRF201.57.21

previously approved after June 30, 2001.26 The FDA has issued scription is required to access this service. For more informa-
draft guidance for industry, which provides additional details tion, visit http://depts.washington.edu/terisweb/teris/.
about what is expected in the new label; this document is open Treating for Two: Safer Medication Use in Pregnancy
for public comment.27 Initiative31 is an initiative developed by the Centers for Dis-
ease Control and Prevention in partnership with the FDA
and others to improve the quality and availability of infor-
mation that can be used to inform clinical decision mak-
PREGNANCY MEDICATION INFORMATION FROM ing for pregnant women, women who could become preg-
ORGANIZATIONS AND DATABASES nant, and health care providers. Treating for Two focuses
To improve access to safety information, other organizations on expanding research about medication safety during preg-
have compiled and summarized available data, including nancy; evaluating evidence through an expert review process
results from pregnancy registries, to serve as a centralized to compare available treatment options for common health
portal for specific medication safety information. Examples conditions and to identify the safer option(s) for disease
of sites where providers can quickly find information about management during pregnancy; and educating women and
a particular medication exposure during pregnancy are health care providers with expert summaries of medication
MotherToBaby,28 REPROTOX,29 TERIS,30 and Treating For safety and disease management. For more information, visit
Two.31 http://www.cdc.gov/pregnancy/meds/treatingfortwo/.31
MotherToBaby,28 a service of the nonprofit Organiza- In the United States and Canada, teratology information
tion of Teratology Information Specialists, provides evidence- is provided to health care providers and the general pub-
based information to women, health care providers, and the lic through a network of professional organizations that are
general public about medications and other exposures during part of the Organization of Teratology Information Specialists
pregnancy and breastfeeding. MotherToBaby provides online (OTIS).28 In Europe, several organizations that provide ter-
fact sheets, available in English and Spanish, for individual atogen information services comprise the membership of the
medications and other exposures. In addition, MotherToBaby European Network of Teratology Information Services.33 The
has a toll-free number (866-626-6847), which can be called for primary mission of these organizations is to provide counsel-
expert consultation. Services are free of charge. For more in- ing regarding the safety of a medication or other agent dur-
formation, visit www.mothertobaby.org. ing pregnancy to women and heath care providers. In addition
REPROTOX29 is an online information system contain- to providing this service, these organizations have attempted
ing summaries on the effects of medications, chemicals, in- to expand available evidence by also conducting pregnancy
fections, and physical agents on pregnancy, reproduction, and registries.
development. The REPROTOX system was developed as a re-
source for clinicians, scientists, and government agencies. RE-
PREGNANCY REGISTRIES
PROTOX requires an annual subscription. For more informa-
tion, visit www.reprotox.org. In contrast to the package insert and its reliance on preap-
TERIS is an online database of summaries of agents and is proval studies, pregnancy registries are observational studies
used by health care providers to evaluate the risks of possible that accrue postmarketing data about the safety of specific
teratogenic exposures in pregnant women. TERIS agent sum- medications or conditions during pregnancy. Pregnancy reg-
maries contain a thorough review of published clinical and istries are designed to assess the safety of human pregnancy
experimental literature and includes a risk assessment devel- exposures for specific approved medications and vaccines,34
oped by an advisory board comprised of nationally recognized and often the impact of disease on pregnancy and pregnancy
authorities in clinical teratology. The database is searched by outcomes is evaluated.
using either generic names or domestic or foreign proprietary Pregnancy registries are not analogous with disease reg-
names. An updated, automated version of Shepard’s Catalog istries and other types of registries designed for surveil-
of Teratogenic Agents 32 is distributed with TERIS. A sub- lance purposes (eg, cancer registries). Pregnancy registries are

54 Volume 61, No. 1, January/February 2016

observational studies that collect data longitudinally, from center facilitates data collection and manages the registry. In
early in pregnancy into infancy, and compare outcomes with general, study-specific office visits are not required. A typi-
an internal or external control group.34,35 Typically, research cal registry collects data on a pregnant woman early in preg-
hypotheses are specified a priori and inferential statistics are nancy, midpregnancy, and just after pregnancy has ended. If
used to evaluate the stated objectives. Pregnancy registries are the pregnancy outcome is a live born neonate, he or she may
generally classified as disease registries that involve pregnant be followed for a period of months to years, depending on
women with the disease of interest or product registries that the suspected potential toxicities and registry objectives. Preg-
focus on specific product or class of products.35 Pregnancy nancy registries may collect outcome information for many
registries are also referred to as pregnancy exposure registries, years after birth, which allows for the evaluation of neurode-
given the focus on product exposure during pregnancy. Preg- velopmental endpoints to help identify or rule out behavioral
nancy registries are often implemented by the manufacturer teratogens. Variations in data collection methods are seen in
and can be required by regulatory agencies as a condition of the examples provided in Table 2.
medication approval or initiated voluntarily after approval. Bias can be introduced if prenatal testing provides evi-
Academia, nonprofit groups, government agencies, and or- dence of abnormalities prior to enrollment. Therefore, enroll-
ganizations that provide teratogen information services also ment early in pregnancy is encouraged because it reduces the
conduct pregnancy registries. likelihood that prenatal testing has already occurred. For this
The primary objective of most pregnancy registries is to reason, some registries exclude women with abnormal prena-
monitor exposed women for major developmental effects or tal tests at the time of enrollment. The prospective orientation
birth defects associated with pregnancy exposures.34 How- reduces the potential for recall bias that may be inherent in
ever, since these studies are designed to recruit women on some case-control studies. In case-control studies, women are
the basis of exposure to a drug or disease of interest and asked about pregnancy exposures to medications after birth
are conducted prospectively (ie, enrollment occurs before when their recall of specific exposures may be influenced
the outcome of pregnancy is known), a range of adverse by the fact that they did or did not have a poor pregnancy
pregnancy outcomes—including fetal growth abnormalities, outcome.
spontaneous abortion or stillbirth, preterm birth, and other Registries may enroll an internal control group (ie, a group
maternal or neonatal complications—can be studied. of pregnant women who have not had the medication ex-
The registries included in Table 224,25,36-42 serve as exam- posure of interest) or may compare findings to an external
ples to highlight some of the most common similarities and comparator, such as published rates from population-based
differences. Included in this set of examples are registries that surveillance systems or unexposed cohorts from other stud-
are conducted by the industry or by universities or terato- ies. In the absence of enrolling an internal comparison group,
gen information services organizations with or without indus- it is critical to understand the limitations and comparability of
try support. Many registries rely on population-based birth the external comparison group. Women who take a particu-
defects rates as an external comparison group; however, to lar medication may differ from women in the general popula-
strengthen the design, several registries have enrolled one or tion in characteristics that also influence their risk for adverse
more internal comparison groups. Data collection methods pregnancy outcomes. For example, women who take a med-
vary across registries in frequency of contact, types of re- ication for hypercholesterolemia or diabetes may be signifi-
porters (woman, prescriber, maternity care provider, pediatric cantly more likely to be obese than the women in the general
care provider), use of physical examinations, and review of population, a characteristic that independently poses an in-
medical records. creased risk for specific congenital malformations. A registry
Most pregnancy registries rely on voluntary reporting by with an internal comparison group of unexposed women, for
health care providers who have eligible women in their prac- whom maternal body mass index (BMI) data are collected, al-
tice. The pregnancy exposure under study may occur infre- lows the registry to account for the contribution of BMI to the
quently; therefore, to optimize enrollment, most pregnancy adverse outcome43 and therefore may help to more accurately
registries are open to anyone in the target population who and validly identify or rule out complications that are due to
meets the entry criteria. Reporters are not required to be the medication itself. Similarly, the underlying maternal dis-
an investigator or otherwise affiliated with the registry. The ease for which the medication is prescribed may contribute to
FDA encourages pregnancy registry sponsors to post a reg- adverse pregnancy outcomes; for example, maternal asthma
istry description and contact information on the FDA Web itself is associated with an increased risk of congenital malfor-
site to raise awareness of the registry and encourage enroll- mations, perinatal mortality, and neonatal hospitalization.44
ment. Currently, 64 pregnancy registries are listed on the FDA Therefore, a comparison group of pregnant women who have
Web site, and this list is updated frequently.42 Table 3 contains the same underlying disease as the exposed group but have not
a listing of pregnancy registries found from a review of the taken the medication of interest can help sort out the potential
FDA’s Web site42 and through Internet searches; this listing problems associated with the drug as opposed to those asso-
has been adapted for clinical use and organized by therapeu- ciated with the disease. Table 2 provides examples of registries
tic area. that use internal and external comparison groups.
Pregnancy registries are designed so that participation is Registries are expected to disseminate their findings to
easy with minimal time and resource involvement. Women inform women and providers.34 Some registries embrace
and/or their health care providers submit data to the registry this aspect, providing interim and final reports of their re-
at various intervals. Data collection is accomplished electron- sults online36,45 or by request, and publish frequently in the
ically, on paper, or by phone; and the registry’s coordinating scientific literature, as data accumulate. For example, the

Journal of Midwifery & Women’s Health r www.jmwh.org 55

 Table 2. Selected Examples of Pregnancy Registries
Registry Data Collection/ Accomplishments and Unique
Description Objectives Population Methods Features
Antiretroviral Study pregnant women Pregnant women with 2 sets of data forms Has enrolled nearly 18,000
Pregnancy Registry36 exposed to any of 38 ARV exposure during submitted women since initiated in
Multiple product different ARVs, (all pregnancy anonymously by 1989.
registry marketed ARVs in woman’s HCP: early One of the longest running
Industry-based United States) in pregnancy and pregnancy registries.
Cosponsored by shortly after Uses population-based data as
manufacturers of 38 pregnancy control group.
antiretrovirals (ARV)

National Examine risks associated Pregnant women with a 1-page questionnaire Enrolled ⬎ 2200 transplant
Transplantation with numerous and history of solid organ about posttransplant recipients (3300 pregnancies)
Pregnancy evolving medical transplantation or pregnancies, since 1991.
Registry37,38 products and whose pregnancy is completed by Includes male exposures.
Disease registry procedures related to fathered by male transplant Contributed to identification of
University-based transplantation transplant recipients coordinator, HCP, or the association between
transplant recipient mycophenolate mofetil
(CellCept) and increased
incidences of spontaneous
abortions and congenital
malformations, resulted in
change from Pregnancy
Category C to D in 2007.

North American Determine frequency of Pregnant women with or 3 brief telephone More than 9,300 women have
Antiepileptic Drug major malformations without AED interviews with been enrolled since this
(AED) Pregnancy in infants exposed to exposure during woman at enrollment, registry was initiated in 1997.
39 AED drugs during pregnancy 7 months’ gestation,
Registry Includes both internal and
Multiple product pregnancy and 8 to 12 weeks external control groups; an
registry after expected date of internal, unexposed control
University-based birth group is a major strength and
Cosponsored by several infrequently seen in
AED manufacturers industry-sponsored registries.
2125 women enrolled since
1999.

OTIS Autoimmune Monitor planned and Pregnant women with Maternal telephone Found no significant difference
Diseases in Pregnancy unplanned RA, psoriasis, interviews: 3 during in major defects and no
Study40,41 pregnancies exposed psoriatic arthritis, pregnancy; at pattern of minor defects
Multiple product to certain Crohn’s disease, outcome; 1 year infant among 64 women with RA
registry medications, to ankylosing follow-up exposed to leflunomide
University- and evaluate the possible spondylitis, and Outcome confirmed by (Arava) during pregnancy
teratogen information teratogenic effect, and multiple sclerosis medical records; compared to 108 unexposed
services-based to follow live-born with or without includes specialized, women with RA and 78
neanates for one year medication exposure blinded infant physical unexposed women without
after birth for these indications examination by RA.
dysmorphologists/ Although based on small
geneticists for major numbers, provides first
and minor defects

(Continued)

56 Volume 61, No. 1, January/February 2016

 Table 2. Selected Examples of Pregnancy Registries
Registry Data Collection/ Accomplishments and Unique
Description Objectives Population Methods Features
human study data and some
reassurance regarding
inadvertent leflunomide
exposure in early pregnancy.
Use of 2 comparison groups
and blinded infant physical
examination are major
strengths of this study.

Ribavirin Pregnancy Monitor pregnancy Pregnant women with 5 data collection time Enrolled 263 pregnancies since
Registry24,25 exposures to ribavirin ribavirin exposure points: early 2004.
Multiple product and evaluate the during pregnancy or pregnancy; Category X product.
registry potential human 6-month period midpregnancy; end of Includes male exposures.
Industry-based teratogenicity of before pregnancy; or pregnancy; infant 6 Long exposure window (6
Cosponsored by all 7 prenatal exposure if similarly exposed and 12 months, from months prior to conception)
manufacturers of through male sexual prescriber, maternity due to the long half-life of
ribavirin in the United partner taking HCP, pediatric HCP ribavirin (Copegus, Rebetol)
States ribavirin Uses population-based data as
control group.

Abbreviations: AED, antiepileptic drug; ARV, antiretroviral; HCP, health care provider; RA, rheumatoid arthritis.

Antiretroviral Pregnancy Registry, which has been operating cific information on the timing and dose of drug exposures
since 1989, uploads their interim report36 twice yearly provid- from pregnancy registries to improve the estimation of risk
ing the most up-to-date results from the registry to health care for developmental toxicity, thereby increasing the usefulness
providers. Most registries publish their data in the scientific of the data in assessing outcomes such as growth alteration,
literature and many publish interim findings, although unfor- structural anomalies, functional/neurobehavioral deficits, or
tunately some wait until the study has ended, which decreases death.
the clinical usefulness of the data.
Commonly, registries conducted by organizations pro- CLINICAL IMPLICATIONS
viding teratogen information services obtain enrollees from
individuals who call the organization seeking counseling re- A health care provider may make a connection between a
garding the safety of a medication or other agent to which the number of women with a specific problem and their com-
woman has already been exposed or might be exposed. For se- mon prenatal medication exposure. For example, Herbst48
lected target exposures, exposed and unexposed comparison first noted the link between in utero exposure to diethyl-
women are enrolled in a registry; the unexposed women form stilbestrol (DES) and clear cell adenocarcinoma in females.
the internal control group. The OTIS Autoimmune Diseases Due in part to Herbst’s observations, DES was withdrawn
in Pregnancy Study40,41 is an example of a registry based in an from the market, and health care providers and women are
organization whose primary function is to deliver teratogen now well aware of this association. An individual health care
information services (Table 2). provider may never encounter a phenomenon such as was
Pregnancy registries are often slow to enroll, and results seen by Herbst,48 particularly if the exposures are rare, the
may not be available for years after the product enters the mar- strength of the exposure-disease relationship is weak, or the
ket. The pace of enrollment may be related to a low prevalence outcome is less striking. However, all health care providers
of eligible women (rare exposures during pregnancy) or may are given the opportunity to study these issues prospectively
reflect a lack of awareness about the registry, including meth- by participating in pregnancy registries. This research activ-
ods for reporting, or both. This lack of information inhibits ity is not limited to the midwife, nurse practitioner, pedia-
the ability of the health care provider to provide evidence- trician, obstetrician-gynecologist, oncologist, or pathologist;
based care to pregnant women. every pregnant woman and health care provider possesses po-
There is much room for improvement in the conduct of tentially valuable data needed by pregnancy registries.
pregnancy registries. In 2009, the OTIS Research Commit- There are several actions that may be taken by health
tee published a position article calling for better data from care providers to address the overall lack of information
pregnancy registries.47 The committee called for more spe- about medication safety during pregnancy. Keeping the

Journal of Midwifery & Women’s Health r www.jmwh.org 57

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Antiinfective HIV/AIDS All antiretroviral Antiretroviral Pregnancy Registry/INC Research, LLC
medications marketed Phone: 800-258-4263
in the United States Web site: http://www.apregistry.com/
for HIV/AIDS
Antiinfective Hepatitis C Ribavirin (includes all Ribavirin Pregnancy Registry/INC Research, LLC
brand and generic Phone: 800-593-2214
products) E-mail: pregnancyregistries@incresearch.com
Web site: www.ribavirinpregnancyregistry.com
Autoimmune Rheumatoid arthritis Tocilizumab (Actemra) OTIS Autoimmune Diseases Study
Phone: 877-311-8972
http://www.pregnancystudies.org/ongoing-pregnancy-
studies/autoimmune-studies/autoimmune-disease-
treatments-pregnancy/
Autoimmune Rheumatoid arthritis Leflunomide (Arava) Leflunomide Pregnancy Registry/OTIS/MotherToBaby
1-877-311-8972
Autoimmune Multiple sclerosis Teriflunomide (Arava) OTIS Autoimmune Diseases Study
Phone: 877-311-8972
http://www.pregnancystudies.org/ongoing-pregnancy-
studies/autoimmune-studies/autoimmune-disease-
treatments-pregnancy/
Autoimmune Systemic lupus Belimumab (Benlysta) Benlysta Pregnancy Registry/GlaxoSmithKline
erythematosus (SLE) Phone: 877-681-6296
Web site: http://pregnancyregistry.gsk.com/belimumab.html
Autoimmune Rheumatoid arthritis Certolizumab OTIS Autoimmune Diseases
Psoriatic arthritis pegol (Cimzia) Phone: 877-311-8972
Ankylosing spondylitis Web site: http://www.pregnancystudies.org/ongoing-
Psoriasis pregnancy-studies/autoimmune-studies/autoimmune-
Crohn’s disease disease-treatments-pregnancy/
Autoimmune Rheumatoid arthritis Etanercept (Enbrel) OTIS Autoimmune Diseases
Psoriatic arthritis Phone: 877-311-8972
Ankylosing spondylitis Web site: http://www.pregnancystudies.org/ongoing-
Psoriasis pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/
Autoimmune Multiple sclerosis Fingolimod (Gilenya) The Gilenya Pregnancy Registry/Novartis Pharmaceuticals
Phone: 877-598-7237
Web site: http://www.gilenyapregnancyregistry.com
Autoimmune Rheumatoid arthritis Adalimumab (Humira) OTIS Autoimmune Diseases
Psoriatic arthritis Phone: 877-311-8972
Ankylosing spondylitis Web site: http://www.pregnancystudies.org/ongoing-
Crohn’s disease pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/

(Continued)

58 Volume 61, No. 1, January/February 2016

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Autoimmune Psoriasis Cyclosporine USP Neoral Pregnancy Registry for Psoriasis and Rheumatoid
Rheumatoid arthritis (Neoral) Modified Arthritis
Gift of Life Institute
Phone: 215-599-2078
Toll-free: 888-522-5581
E-mail: npr.registry@giftoflifeinstitute.org
Web site: http://www.ntpr.giftoflifeinstitute.org
Autoimmune Severe rheumatoid Abatacept (Orencia) OTIS Autoimmune Diseases
arthritis Phone: 877-311-8972
Web site: http://www.pregnancystudies.org/ongoing-
pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/
Autoimmune Psoriatic arthritis Apremilast (Otezla) OTIS Autoimmune Diseases
Psoriasis Phone: 877-311-8972
Web site: http://www.pregnancystudies.org/ongoing-
pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/
Autoimmune Psoriatic arthritis Ustekinumab (Stelara) OTIS Autoimmune Diseases
Psoriasis Phone: 877-311-8972
Web site: http://www.pregnancystudies.org/ongoing-
pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/
Autoimmune Multiple sclerosis Dimethyl fumarate Tecfidera Pregnancy Exposure Registry
(Tecfidera) Phone: 866-810-1462
Web site: https://www.tecfiderapregnancyregistry.com/
Autoimmune Rheumatoid arthritis Tofacitinib (Xeljanz) OTIS Autoimmune Diseases
Phone: 877-311-8972
Web site: http://www.pregnancystudies.org/ongoing-
pregnancy-studies/autoimmune-studies/autoimmune-
disease-treatments-pregnancy/
Dermatologic Psoriasis Cyclosporine USP Neoral Pregnancy Registry for Psoriasis and Rheumatoid
Rheumatoid arthritis (Neoral) Arthritis
Gift of Life Institute
Phone: 888-522-5581
E-mail: npr.registry@giftoflifeinstitute.org
Web site: http://www.ntpr.giftoflifeinstitute.org
Dermatologic Antibacterial for skin Telavancin (Vibativ) Vibativ Pregnancy Registry
infection Phone: 888-658-4228
Web site: www.clinicaltrials.gov
Dermatology Psoriasis Acitretin T.A.P.P. (Take Action to Prevent Pregnancy)
Pregnancy Monitoring Program for Acitretin
Phone: 855-850-2138
Web site: http://www.tevagenerics.com/acitretin

(Continued)

Journal of Midwifery & Women’s Health r www.jmwh.org 59

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Endocrine/ Type 2 diabetes Exenatide (Bydureon) Exenatide Pregnancy Registry/INC Research LLC
metabolic Phone: 800-633-9081
Web site: http://www.exenatidepregnancyregistry.com/
Endocrine/ Type 2 diabetes Sitagliptin phosphate Merck Pregnancy Registry Program
metabolic plus metformin Phone: 800-986-8999
hydrochloride Web site: www.merckpregnancyregistries.com/januvia.html
(Janumet)
Endocrine/ Type 2 diabetes Sitagliptin phosphate Merck Pregnancy Registry Program
metabolic (Januvia) Phone: 800-986-8999
Web site: www.merckpregnancyregistries.com/januvia.html
Genetic MPSI Laronidase MPSI Registry/Genzyme Corporation
Hurler’s syndrome (Aldurazyme) Phone: 617-591-5500
Scheie’s syndrome E-mail: help@mpsiregistry.com
Hurler-Scheie syndrome Web site: http://www.lsdregistry.net/mpsiregistry
Genetic Fabry disease Agalsidase beta Fabry Registry/Genzyme Corporation
(Fabrazyme) Phone: 617-591-5500
E-mail: help@FabryRegistry.com
Web site: https://www.registrynxt.com/fabry/Pages/Home.aspx
Genetic Pompe disease Alglucosidase alfa Pompe Disease Registry/Genzyme Corporation
(GAA deficiency) (Myozyme) Phone: 617-591-5500
E-mail: help@PompeRegistry.com
Web site:
https://www.registrynxt.com/Pompe/Pages/Home.aspx
Genetic Maroteaux-Lamy Galsulfase (Nagazyme) MPS VI Clinical Surveillance Program/BioMarin
syndrome also known Pharmaceutical
as polydystrophic Phone: 415-506-6849
dwarfism or MPS VI Web site:
https://clinicaltrials.gov/ct/show/NCT00214773?order=2
Hematologic ITP Romiplostim (Nplate) Nplate Pregnancy Exposure Registry/Amgen
Phone: 800-772-6436
Web site: http://www.nplate.com/patient/how-nplate-may-
help/taking-nplate.html
Hematologic ITP Eltrombopag Promacta Pregnancy Registry/GlaxoSmithKline
(Promacta) Phone: 877-379-3718
Web site: https://clinicaltrials.gov/ct2/show/NCT01064336
Musculoskeletal Osteoporosis Penosumab (Prolia) Amgen’s Pregnancy Surveillance Program
Phone: 800-772-6436
Neurologic Epilepsy Antiepileptic drugs AED Pregnancy Registry/Massachusetts General Hospital
Phone: 888-233-2334
Web site: http://www.massgeneral.org/aed/
Neurologic Epilepsy Eslicarbazepine acetate AED Pregnancy Registry/Massachusetts General Hospital
(Aptiom) Phone: 888-233-2334
Web site: http:www.massgeneral.org/aed/

(Continued)

60 Volume 61, No. 1, January/February 2016

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Neurologic Partial onset seizures Levetiracetam (Keppra) UCB AED Pregnancy Registry/INC Research, LLC
(No longer accepting Phone: 888-537-7734
new registrations) Web site:
http://www.clinicaltrials.gov/CT2/show/NCT00345475
Neurologic Epilepsy, neuropathic Pregabalin (Lyrica) AED Pregnancy Registry/Massachusetts General Hospital
pain Phone: 888-233-2334
Web site: www.massgeneral.org/aed/
Neurologic Migraine headaches Rizatriptan (Maxalt) Merck Pregnancy Registry Program
Phone: 800-986-8999
Web site: www.merckpregnancyregistries.com/maxalt.html
Neurologic Excessive sleepiness Armodafinil (Nuvigil) Nuvigil Pregnancy Registry/Teva Pharmaceuticals
associated with: Phone: 866-404-4106
obstructive sleep Web site: http://www.nuvigilpregnancyregistry.com/
apnea, hypopnea
syndrome, narcolepsy,
shift work sleep
disorder
Neurologic Excessive sleepiness Modafinil (Provigil) Provigil Pregnancy Registry/Teva Pharmaceuticals
associated with: Phone: 866-404-4106
obstructive sleep Web site: http://provigilpregnancyregistry.com/
apnea, hypopnea
syndrome, narcolepsy,
shift work sleep
disorder
Neurologic Fibromyalgia Milnacipran (Savella) Savella Pregnancy Registry/INC Research
Phone: 877-643-3010
E-mail: pregnancyregistries@incresearch.com
Web site: www.savellapregnancyregistry.com
Oncology Cancer and childbirth Cancer and cancer Cooper Health
registry treatments Phone: 877-635-4499
Web site: www.cooperhealth.org/departments-
programs/cancer-and-pregnancy
Oncology Breast cancer Ado-trastuzumab MotHER Pregnancy Registry/INC Research, LLC
emtansine (Kadcyla) Phone: 800-690-6720
Web site: http://www.motherpregnancyregistry.com/
Oncology Breast cancer Pertuzumab (Perjeta) MotHER Pregnancy Registry/INC Research, LLC
Phone: 800-690-6720
Web site: http://www.motherpregnancyregistry.com/
Organ transplant Immunosuppressive Mycophenolate Mycophenolate Pregnancy Registry
drug (renal (Cellcept) National Transplantation Pregnancy Registry
transplant) Phone: 800-617-8191
Web site: www.mycophenolatepregnancyregistry.com

(Continued)

Journal of Midwifery & Women’s Health r www.jmwh.org 61

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Organ transplant Immunosuppressive Mycophenolate Mycophenolate Pregnancy Registry
drug (renal (Myfortic) National Transplantation Pregnancy Registry
transplant) Phone: 800-617-8191
Web site: www.mycophenolatepregnancyregistry.com
Organ transplant Immunosuppressive Belatacept (Nulojix) National Transplantation Pregnancy Registry
drug (renal Gift of Life Institute
transplant) Phone: 877-955-6877
Web site: http://www.ntpr.giftoflifeinstitute.org/
Organ transplant Transplants Pregnant women who National Transplantation Pregnancy Registry
anti-rejection medicines are transplant Gift of Life Institute
recipients or whose Phone: 877-955-6877
pregnancy is fathered E-Mail: ntpr@giftoflifeinstitute.org
by a transplant Web site: www.ntpr.giftoflifeinstitute.org
recipient
Psychiatric Atypical antipsychotics Aripiprazole (AbilifY) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Atypical antipsychotics CLozapine (Clozaril) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Major depressive Duloxetine HCl Cymbalta Pregnancy Registry/INC Research, LLC
disorder (Cymbalta) Phone: 866-814-6975
generalized anxiety E-mail: pregnancyregistries@incresearch.com
disorder Web site: http://www.cymbaltapregnancyregistry.com/
diabetic peripheral
neuropathic pain
fibromyalgia
Psychiatric Psychiatric conditions Iloperidone (Fanapt) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions Ziprasidone (Geodon) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry

(Continued)
62 Volume 61, No. 1, January/February 2016
 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Psychiatric Psychiatric conditions Paliperidone (Invega) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions Lurasidone (Latuda) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions Risperidone (Risperdal) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions Asenapine (Saphris) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions Quetiapine (Seroquel) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Psychiatric Psychiatric conditions OLanzapine (Zyprexa) National Pregnancy Registry for Atypical Antipsychotics
Center for Women’s Mental Health, Mass. General Hospital
Phone: 866-961-2388
E-mail: registry@womensmentalhealth.org
Web site: www.womensmentalhealth.org/clinical-and-research-
programs/pregnancyregistry
Respiratory Asthma Long-acting beta agonist MotherToBaby Pregnancy Studies conducted by OTIS
and short-acting beta Phone: 877-311-8972
agonist products Web site:
http://www.pregnancystudies.org/ongoing-pregnancy-
studies/asthma-study/asthma-treatments-pregnancy/

(Continued)

Journal of Midwifery & Women’s Health r www.jmwh.org 63

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Respiratory Asthma Montelukast (Singulair) Merck Pregnancy Registry Program
Phone: 800-986-8999
Web site: www.merckpregnancyregistries.com/singulair.html
Respiratory Asthma Omalizumab (Xolair) EXPECT Xolair Pregnancy Registry
Phone: 866-496-5247 Option 3
Web site: http://www.xolairpregnancyregistry.com/
Vaccine Prevention of seasonal Influenza virus vaccine Seasonal Influenza Vaccine Pregnancy
influenza (Fluarix, Fluarix Registry/GlaxoSmithKline
Quadrivalent) Phone: 888-825-5249
Web site: http://pregnancyregistry.gsk.com/
seasonalInfluenzaVaccines.html
Vaccine Prevention of influenza Influenza vaccine The Flu Vaccine Pregnancy Registry/PPD, Inc.
(Flucelvax) Phone: 877-413-4759
E-mail: NovartisVaccinePregnancyRegistries@ppdi.com
Web site: https://www.ppdi.com/Services/Post-
Approval/Patient-Registries-and-Observational-
Studies/Pregnancy-Registries/Registry-Descriptions
Vaccine Prevention of seasonal Influenza virus vaccine Seasonal Influenza Vaccine Pregnancy Registry
influenza suspension Phone: 888-825-5249
(Flulaval, Flulaval Web site: http://pregnancyregistry.gsk.com/
Quadrivalent) seasonalInfluenzaVaccines.html
Vaccine Prevention of human Human Papillomavirus Merck Gardasil Pregnancy Registry
papillomavirus Quadrivalent (Types Phone: 800-986-8999
6, 11, 16, and 18) Web site: www.merckpregnancyregistries.com/gardasil.html
Vaccine,
Recombinant
(Gardasil)
Vaccine Prevention of meningitis Meningococca Menactra Vaccine Pregnancy Registry
polysaccharide Phone: 800-822-2463
diptheria toxoid
(Menactra)
Vaccine Prevention of meningitis Meningitis vaccine Menveo Pregnancy Exposure Registry
(Menveo) Phone: 877-311-8972
Web site: http://www.pregnancystudies.org/ongoing-
pregnancy-studies/influenza-vaccine-antiviralmedications-
study/
Vaccine Prevention of meningitis Meningitis vaccine Menveo Vaccine Pregnancy Registry
(Menveo) Phone: 877-413 4759
E-mail: NovartisVaccinePregnancyRegistries@ppdi.com
Web site: http://www.ppdi.com/Services/Post-
Approval/Patient-Registries-and-Observational-
Studies/Pregnancy-Registries/Registry-Descriptions.aspx

(Continued)

64 Volume 61, No. 1, January/February 2016

 Table 3. Pregnancy Exposure Registries from Internet Searches and the List of Pregnancy Exposure Registries on the FDA Web Site43
Medicine
or Disease
Drug System Medical Condition Registry Focus Registry Contact Information
Vaccine Prevention of hepatitis A Combined hepatitis A Twinrix Pregnancy Registry/GlaxoSmithKline
Prevention of hepatitis B [inactivated] and Phone: 888-825-5249
hepatitis B Web site: http://pregnancyregistry.gsk.com/twinrix.html
[recombinant]
vaccine (Twinrix)
Vaccine Prevention of meningitis Meningitis vaccine MotherToBaby Pregnancy Studies conducted OTIS
(Menveo) Phone: 877-311-8972
Web site: www.pregnancystudies.org/
Vaccine Prevention of measles, Measles, Mumps, The Pregnancy Registry for Varicella Zoster Virus
mumps, rubella and Rubella and Varicella (VZV)-containing Vaccines/Merck & Company, Inc.
chicken pox Virus Vaccine Live Phone: 800-986-8999
(Proquad) Web site: www.merckpregnancyregistries.com/varivax.html
Vaccine Prevention of Varicella Virus Vaccine The Pregnancy Registry for Varicella Zoster Virus
chickenpox Live (Varivax) (VZV)-containing Vaccines/Merck & Company, Inc.
Phone: 800-986-8999
Web site: www.merckpregnancyregistries.com/varivax.html
Vaccine Prevention of herpes Zoster Vaccine Live The Pregnancy Registry for Varicella Zoster Virus
zoster (Zostavax) (VZV)-containing Vaccines/ Merck & Company, Inc.
Phone: 800-986-8999
Web site: www.merckpregnancyregistries.com/varivax.html

Abbreviations: GAA, acid alpha-glucosidase; ITP, idiopathic thrombocytopenic purpura; MPSI, mucopolysaccharidosis type I; MPS VI, mucopolysaccharidosis VI; OTIS,
Organization of Teratology Information Specialists; VAMPSS, Vaccines and Medications in Pregnancy Surveillance Study; VZV, varicella zoster virus.
Source: Internet searches and U.S. DHHS. Food and Drug Administration. Women’s Health Research. List of Pregnancy Exposure Registries.42

list of pregnancy registries42 near the telephone, computer, CONCLUSION

and/or patient medical records (Table 3) will enable rapid Health care providers are encouraged to evaluate each preg-
identification of existing registries, preferably during the nant woman as a potential registry participant if she has been
woman’s office visit. Assisting the woman with contacting exposed to one of the medications for which a registry is avail-
the registry during her appointment facilitates enrollment able; if she is not exposed, she may be evaluated to determine
because postponing can lower enrollment rates. Even if the eligibility to contribute data as a member of an unexposed
woman discontinues the medication prior to pregnancy, she control group. When health care providers enroll pregnant
may be eligible to participate in a registry as a member of the women in pregnancy registries, they add to the body of
unexposed control group. evidence that will eventually be used to inform their practice.
Locating an appropriate pregnancy registry can be accom- As these studies accumulate data and report findings, this
plished in several ways, such as referring to Table 3, search- important information will appear in the scientific literature,
ing the pregnancy registry listing on the FDA Web site,42 in clinical practice aids such as the MotherToBaby28 online
or contacting MotherToBaby.28 MotherToBaby28 is a conve- fact sheets, and eventually, in the product package inserts as
nient resource for questions about whether there is a registry the new labeling regulations are implemented. If health care
for a drug of concern (www.mothertobaby.org or 866-626- providers increasingly participate in reporting to pregnancy
6847). MotherToBaby provides information about ongoing registries, the timeliness of receiving this information will be
pregnancy registries for a particular exposure, in addition to greatly improved.
providing summary information about pregnancy exposures.
In addition, health care providers are encouraged to contact AUTHORS
administrators and/or providers of electronic medical records
to incorporate flags or reminders to facilitate enrollment of Susan Sinclair, PhD, MPH, is Associate Professor at the Uni-
women in the appropriate pregnancy exposure registry if a versity of North Carolina at Wilmington in the Clinical Re-
drug is electronically prescribed and/or prescribed within the search Program. She is also a consultant epidemiologist to
study protocol-specified window of exposure. INC Research (Wilmington, NC). She serves as the principal
investigator for the Ribavirin Pregnancy Registry.

Journal of Midwifery & Women’s Health r www.jmwh.org 65

Richard Miller, PhD, is Professor of Obstetrics and Gyne- medication during pregnancy: A population-based study among
cology, Environmental Medicine, and Pathology and Clinical 19874 Danish women. Eur J Clin Pharmacol. 2006;62(7):547-553.
Laboratory Medicine at the University of Rochester School 9.Schirm E, Meijer W, Tobi H, deJong-van den Berg L. Drug use by preg-
nant women and comparable non-pregnant women in The Nether-
of Medicine and Dentistry, New York. He is also Director
lands with reference to the Australian classification system. Eur J Ob-
of MotherToBaby URMedicine (NY, NJ, PA Teratogen In- stet Gynecol Reprod Biol. 2004;114(2):182-188.
formation Service). He is Past President of the US Teratol- 10.Finer LB, Zolna MR. Shifts in intended and unintended pregnancies
ogy Society, Chair of the OTIS-ENTIS International Research in the United States, 2001-2008.Am J Public Health. 2014;104(suppl
Consortium. 1):S43-S48.
11.Miller RK, Peters PW, Schaefer CE. General commentary on drug
Christina Chambers, PhD, MPH, is Professor in the De- therapy and drug risks during pregnancy. In: Schaefer C, Peters P,
partment of Pediatrics and Family and Preventive Medicine and Miller RK, eds. Drugs During Pregnancy and Lactation. 2nd ed.
at the University of California, San Diego (UCSD) School Burlington, MA: Elsevier; 2007:2-24.
of Medicine. Dr. Chambers has worked as an epidemiolo- 12.Wyszynski DF. Pregnancy exposure registries: Academic opportuni-
ties and industry responsibility. Birth Defects Res A Clin Mol Teratol.
gist with MotherToBaby CA and the national MotherToB-
2009;85(1):93-101.
aby Organization for the last 16 years. Dr. Chambers is a past 13.Lenz W. A short history of thalidomide embryopathy. Teratology
President of the US Teratology Society, past president of the 1988;38:203-215.
Organization of Teratology Information Specialists (OTIS), 14.Zomerdijk IM, Ruiter R, Houweling LMA, et al. Isotretinoin expo-
and leads the OTIS collaborative research center located at sure during pregnancy: A population-based study in The Netherlands.
UCSD. BMJ Open. 2014; 4(11):e005602. doi: 10.1136/bmjopen-2014-005602.
Available at: http://bmjopen.bmj.com/content/4/11/e005602.full. Ac-
Elizabeth Cooper, CNM, EdD, FACNM, is Professor Emeritus cessed April 15, 2015.
of Obstetrics and Gynecology at the University of Rochester 15.Uhl K, Cox E, Rogan R, et al. Thalidomide use in the U.S. : experi-
School of Medicine and Dentistry, New York. She is the ence with pregnancy testing in the S.T.E.P.S. programme. Drug Saf.
founder of the University of Rochester Medical Center’s mid- 2006;29(4):321-329.
16.Thorpe PG, Gilboa SM, Hernandez-Diaz S, et al. Medications in
wifery practice in 1975 and was Director of the Department
the first trimester of pregnancy: Most common exposures and criti-
of Obstetrics and Gynecology’s Midwifery Division from 1992 cal gaps in understanding fetal risk. Pharmacoepidemiol Drug Saf.
to 2013. 2013;22(9):1013-1018.
17.Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the ter-
atogenicity of medications in human pregnancy. Am J Med Genet C
CONFLICTS OF INTEREST Semin Med Genet. 2011;157C(3):175-182.
Drs. Sinclair and Miller are paid consultants to INC Research 18.United States Department of Health and Human Services. Code of
Federal Regulations, 45 CFR 46.204 (Subpart B). Research involving
in Wilmington, North Carolina, which manages the Ribavirin
pregnant women or fetuses. US DHHS Web site. Available at: http://
Pregnancy Registry and the Antiretroviral Pregnancy Registry www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.204
on behalf of its industry sponsors. Dr. Miller is also a mem- Published January 15, 2009. Updated January15, 2010. Accessed April
ber of the Scientific Board of the MotHER Pregnancy Reg- 14, 2015.
istry. Drs. Chambers and Cooper have no conflicts of interest 19.United States Department of Health and Human Services. Food and
to disclose Drug Administration (FDA). Reviewer Guidance: Evaluating the Risks
of Drug Exposure in Human Pregnancies. FDA Web site. Available at:
http://www.fda.gov/downloads/scienceresearch/specialtopics/women
REFERENCES shealthresearch/ucm133359.pdf. Published April 2005. Accessed
April 14, 2015.
1.Mitchell AA, Gilboa SM, Werler MM, et al. Medication use during 20.PDR.net. Available at: http://www.pdr.net/. Published 2015. Accessed
pregnancy, with particular focus on prescription drugs: 1976-2008. April 14, 2015.
Am J Obstet Gynecol. 2011;205(1):51.e1-e8. 21.U.S. DHHS. Food and Drug Administration (FDA). Code of Fed-
2.Daw JR, Hanley GE, Greyson DL, Morgan SG. Prescription drug use eral Regulations, 21CFR. Labeling Requirements for Prescription
during pregnancy in developed countries: A systematic review. Phar- Drugs and/or Insulin. Available at: http://www.accessdata.fda.gov/
macoepidemiol Drug Saf. 2011;20(9):895-902. scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=201.57. Published on
3.Andrade SE, Gurwitz JH, Davis RL, et al. Prescription drug use in preg- April 1, 2013. Updated September 1, 2014. Accessed April 15,
nancy. Am J Obstet Gynecol. 2004;191(2):398-407. 2015.
4.Gagne JJ, Maio V, Berghella V, Louis DZ, Gonnella JS. Prescription 22.U.S. DHHS. Food and Drug Administration. FDA issues final rule on
drug use during pregnancy: A population-based study in Regione changes to pregnancy and lactation labeling information for prescrip-
Emilia-Romagna, Italy. Eur J Clin Pharmacol. 2008;64(11):1125- tion drug and biological product (press announcement). Available at:
1132. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/
5.Lacroix I, Damase-Michel C, Lapeyre-Mestre M, Montastruc ucm425317.htm. Published December 3, 2014. Updated December
JL. Prescription of drugs during pregnancy in France. Lancet. 12, 2014. Accessed April 15, 2015.
2000;356(9243):1735-1736. 23.Walfisch A, Sermer C, Matok I, Einarson A, Koren G. Perception
6.Bakker MK, Jentink J, Vroom F, VanDen Berg PB, DeWalle HE, of teratogenic risk and the rated likelihood of pregnancy termina-
DeJong-Van Den Berg LT. Drug prescription patterns before, dur- tion: Association with maternal depression. Can J Psychiatry. 2011
ing and after pregnancy for chronic, occasional and pregnancy-related Dec;56(12):761-767.
drugs in the Netherlands. BJOG. 2006;113(5):559-568. 24.Sinclair Roberts S, Jones JK, Miller RK, et al. An update from the Rib-
7.Kulaga S, Zargarzadeh AH, Bérard A. Prescriptions filled dur- avirin Pregnancy Registry: What have we learned after 9 years of en-
ing pregnancy for drugs with the potential of fetal harm. BJOG. rollment? Hepatology. 2013;58(6): 1394A-1395A.
2009;116(13):1788-1795. 25.Roberts SS, Miller RK, Jones JK, et al. The Ribavirin Pregnancy Reg-
8.Olesen C, Thrane N, Henriksen TB, Ehrenstein V, Olsen J. Associ- istry: Findings after 5 years of enrollment, 2003-2009. Birth Defects
ations between socio-economic factors and the use of prescription Res A Clin Mol Teratol. 2010;88(7):551-559.

66 Volume 61, No. 1, January/February 2016

26.Federal Register. Content and Format of Labeling for Human DrugSafety/PostmarketDrugSafetyInformationforPatientsand
Prescription Drug and Biological Products; Requirements for Providers/ucm124776.htm. Published May 16, 2008. Updated
Pregnancy and Lactation Labeling. Final Rule / Vol. 79, No. 233 / August 15, 2013. Accessed April 15, 2015.
Thursday, December 4, 2014. Docket No. FDA-2006-N-0515. Avail- 39.Hernández-Dı́az S, Smith CR, Shen A, et al. Comparative safety of
able at: https://www.federalregister.gov/articles/2014/12/04/2014- antiepileptic drugs during pregnancy. Neurology. 2012;78(21):1692-
28241/content-and-format-of-labeling-for-human-prescription- 1699.
drug-and-biological-products-requirements-for#h-59. Published 40.Organization of Teratogen Information Specialists (OTIS). Moth-
December 12, 2014. Accessed April 15, 2015. erToBaby. Autoimmune Diseases in Pregnancy Studies. Available
27.U.S. DHHS. Food and Drug Administration. Pregnancy, Lactation, at: http://www.pregnancystudies.org/ongoing-pregnancy-studies/
and Reproductive Potential: Labeling for Human Prescription autoimmune-studies/. Published 2015. Accessed April 14, 2015.
Drug and Biological Products —Content and Format. Draft 41.Chambers CD, Johnson DL, Robinson LK, et al. Birth outcomes
Guidance for Industry. Available at: http://www.fda.gov/downloads/ in women who have taken leflunomide during pregnancy. Arthritis
Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ Rheum. 2010;62:1494-1503.
UCM425398.pdf Published December 2014. Accessed April 14, 2015. 42.Bandoli G, Johnson DL, Jones KL, et al. Potentially modifiable risk fac-
28.Organization of Teratogen Information Specialists (OTIS) MotherTo- tors for adverse pregnancy outcomes in women with psoriasis. Br J
Baby. Available at: http://www.mothertobaby.org/. Published 2012. Ac- Dermatol. 2010;163(2):334-339.
cessed April 14, 2015. 43.U.S. DHHS. Food and Drug Administration. FDA Web site. Women’s
29.Reprotox. Available at: https://reprotox.org/. Accessed April 14, Health Research. List of Pregnancy Exposure Registries. [online].
2015. FDA Web site. Available at: http://www.fda.gov/ScienceResearch/
30.TERIS. Available at: http://depts.washington.edu/terisweb/teris/. Ac- SpecialTopics/WomensHealthResearch/ucm134848 Updated Febru-
cessed April 14, 2015. ary 15, 2015. Accessed April 15, 2015.
31.Centers for Disease Control and Prevention. Treating for two: 44.Marengo L, Farag NH, Canfield M. Body mass index and birth defects:
Safer medication use in pregnancy initiative. http://www.cdc.gov/ Texas, 2005-2008. Matern Child Health J. 2013;17(10):1898-1907.
pregnancy/meds/treatingfortwo/. Accessed April 14, 2015. 45.Murphy VE, Wang G, Namazy JA, et al. The risk of congenital mal-
32.Shepard TH: Catalog of Teratogenic Agents, 13th ed. Baltimore, MD: formations, perinatal mortality and neonatal hospitalisation among
The Johns Hopkins University Press; 2010. pregnant women with asthma: A systematic review and meta-analysis.
33.European Network of Teratology Information Services (ENTIS). Avail- BJOG. 2013;120(7):812-822.
able at: http://www.entis-org.eu/. Accessed April 14, 2015. 46.GlaxoSmithKline Pregnancy Registries. Belimumab (Benlysta)
34.U.S. DHHS. Food and Drug Administration. Guidance for Industry: Pregnancy Registry. Belimumab Pregnancy Registry Interim Report
Establishing Pregnancy Exposure Registries. August 2002. Available at: 2014. Available at: http://pregnancyregistry.gsk.com/documents/
http://www.fda.gov/downloads/drugs/guidancecomplianceregulatory Belimumab Pregnancy Registry Interim Report 2014.pdf. Published
information/guidances/ucm071639.pdf Accessed April 15, 2015. August 14, 2015. Accessed April 14, 2015.
35.Gliklich RE, Dreyer NA, eds. Registries for Evaluating Patient Out- 47.Briggs GG, Polifka J; Research Committee, Organization of Teratology
comes: A User’s Guide. 2nd ed. Rockville, MD: Agency for Healthcare Information Specialists. Better data needed from pregnancy registries.
Research and Quality; 2010. Birth Defects Res A Clin Mol Teratol. 2009;85(2):109-111.
36.Antiretroviral Pregnancy Registry Interim Report. Available at: 48.Herbst AL, Scully RE. Adenocarcinoma of the vagina in adoles-
http://www.apregistry.com/forms/interim report.pdf. Issued Decem- cence. A report of 7 cases including 6 clear-cell carcinomas (so-called
ber 2014. Accessed April 15, 2015. mesonephromas). Cancer. 1970;25:745-757.
37.Coscia LA, Constantinescu S, Moritz MJ, et al. Report from the
National Transplantation Pregnancy Registry (NTPR): Outcomes of Continuing education units (CEUs) for this article are of-
pregnancy after transplantation. Clin Transpl. 2010:65-85. fered as part of a CEU theme issue. To obtain CEUs on-
38.US Food and Drug Administration (FDA). FDA Alert [5/16/ line, please visit www.jmwhce.org. A CEU form that can
2008] - Inosine Monophosphate Dehydrogenase Inhibitors (IMPDH)
Immunosuppressants. Information for Healthcare Professionals: My-
be mailed or faxed is available in the print edition of this
cophenolate Mofetil (marketed as CellCept) and Mycophenolic Acid issue.
(marketed as Myfortic). Available at: http://www.fda.gov/Drugs/

Journal of Midwifery & Women’s Health r www.jmwh.org 67