You are on page 1of 9

Am J Clin Dermatol (2013) 14:351358

DOI 10.1007/s40257-013-0041-9


The Management of Acne Vulgaris in Pregnancy

Fiona M. Meredith Anthony D. Ormerod

Published online: 31 August 2013

 Springer International Publishing Switzerland 2013

Abstract Acne vulgaris is a common condition in adolescence and also for many women of childbearing age.
The management of acne in pregnancy is complicated by
the lack of clinical studies and pharmacokinetic data in
this patient population and safety concerns regarding
retinoid use in pregnancy. Of primary concern to both
patients and clinicians is the safety profile of medications
used during pregnancy. This review seeks to clarify what
management options are available to treat acne during
pregnancy and what data are available to guide decision
making. Topical treatments are considered the safest
option during pregnancy. They have the best safety profile
and minimize the levels of systemic absorption, and
therefore the least risk of fetal exposure. If these are
applied properly with a strong emphasis on adherence,
excellent results can be achieved.

1 Introduction
1.1 Background
Acne vulgaris is an extremely common condition in the
adolescent population, with 1520 % of young people
having moderate to severe disease [1, 2]. This tends to
settle in adulthood but there is a group of women who
continue to have ongoing acne or develop acne for the first
F. M. Meredith
Department of Dermatology, Aberdeen Royal Infirmary,
Foresterhill, Aberdeen AB25 2ZN, UK
A. D. Ormerod (&)
Division of Applied Medicine, University of Aberdeen,
Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UK

time when older [3]. One German study found that acne
persisted into the 20s and 30s in around 64 % and 43 % of
individuals, respectively [4]. A British study found 12 % of
women had facial acne that appeared to persist into middle
age [5].
In women with both new and pre-existing acne, the
management of the condition during pregnancy can be
particularly challenging as there are limited therapeutic
options available to them. Owing to the hazards associated
with clinical research in a pregnant population, no trials of
acne treatment have been published in this patient group.
This means that relevant safety data have been extrapolated
from the use of medications for other reasons. The available evidence is mainly restricted to observational studies
and often with small samples sizes. There are pregnancyexposure registries that collect data on the use of certain
medications in pregnancy. However, there are no relevant
registries for acne treatments [6].
Acne severity can vary significantly, from mild
comedonal disease to severe, scarring, inflammatory
lesions that can be accompanied by systemic symptoms.
Treatment decisions during pregnancy will inevitably be
influenced by the severity of the acne balanced against the
safety profile of proposed treatments. In addition, as
approximately half of the six million pregnancies in the
USA each year are unplanned, many women will be
exposed to drugs before they know they are pregnant [7]. It
is also important to note the stage of pregnancy at which
the exposure occurs as this will alter the risk substantially
depending on the medication.
Many guidelines have been created for the management
of acne [8, 9]. The aim of this review is to review the
published evidence to identify effective treatments for acne
and to then assess the safety of using these therapies in


F. M. Meredith, A. D. Ormerod

Table 1 Summary of US FDA categories for medication use in pregnancy [15]



Controlled studies show no risk: Adequate, well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in
any trimester of pregnancy

No evidence of risk in humans: Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal
abnormalities despite adverse findings in animals,
In the absence of adequate human studies, animal studies show no fetal risk. The chance of fetal harm is remote, but remains a

Risk cannot be ruled out: Adequate, well-controlled human studies are lacking, and animal studies have shown a risk to the fetus or
are lacking as well

Positive evidence of risk: Studies in humans, or investigational or post-marketing data, have demonstrated fetal risk. Nevertheless,
potential benefits from the use of the drug may outweigh the potential risk. For example, the drug may be acceptable if needed in a
life-threatening situation or serious disease for which safer drugs cannot be used or are ineffective

Contraindicated in pregnancy: Studies in animals or humans, or investigational or post-marketing reports, have demonstrated positive
evidence of fetal abnormalities or a risk that clearly outweighs any possible benefit to the patient

There is a chance of fetal harm if the drug is administered during pregnancy, but the potential benefits may outweigh the potential risk

1.2 Literature Review

The following sources were searched: Ovid, MEDLINE,
EMBASE, and Pubmed. No date restrictions were applied
but studies were limited to English language only. The
keywords used were pregnancy; acne; teratogenicity;
safety; guidelines; retinoids; isotretinoin; topical;
steroids; antibiotics; laser; light; benzoyl peroxide;
salicyclic acid; congenital; tetracycline; clindamycin; erythromycin; azithromycin; and azelaic acid.
Hand searches of the references of retrieved papers were
also performed, as were online searches of the UKTIS,
ORTIS, MIMS, and the British National Formulary (see
Useful Resources section).
1.3 Physiologic Skin Changes in Pregnancy
There are many physiologic changes in the skin associated
with pregnancy. Sebaceous and eccrine gland secretion
increases, whereas apocrine gland activity decreases [10,
11]. In a small, prospective cohort study of 140 pregnant
women, of the 19 patients with acne 11 noted regression of
their disease and 8 observed an aggravation of their skin
during pregnancy [12].

leading to decreased total plasma concentrations. However,

as a result of decreased protein binding, there is more
available free drug that compensates for these factors,
limiting their impact [14].
1.5 Current Guidance
In 1979, the US Food and Drug Administration (FDA)
introduced a pregnancy category system to guide safe
prescription of medications during pregnancy [15]. The
criteria are summarized in Table 1. Whilst helpful, some
think that the categorization is overly simplistic and lacks
information about the severity, nature, and available
treatments of any possible effect on the fetus [16]. The
American Society of Teratology proposed that the classification system was changed to give more evidence-based
narrative statements [17].
In 2008, the FDA proposed major revisions to drug
labeling that will eliminate the current pregnancy categories and provide more detailed information to guide prescribing. As of February 2011, the Final Rule is in the
writing and clearance process [18].
Taking into account these limitations, the FDA categories for some commonly used acne preparations are summarized in Table 2.

1.4 Pharmacokinetics in Pregnancy

Physiologic changes in pregnancy alter the absorption,
distribution, and clearance of medications [13]. This is due
to a variety of factors including delayed gastric emptying,
increased plasma volume, increased renal blood flow, and
the induction of the hepatic cytochrome P450 system by
estrogens and progesterones [13]. In general, these changes
cause decreased absorption and increased elimination

2 Topical Preparations
Topical agents are the mainstay of treatment for mild to
moderate acne [9]. Some topical medications do not have a
pregnancy category as systemic absorption is generally
considered to be minimal, unless use is extensive, intensive, or prolonged [19]. More recently, many combination

Management of Acne Vulgaris in Pregnancy

Table 2 US FDA categories of
medication used in acne
management [18, 19]

In pregnancy class C, if dose

exceeds recommended daily



Oral medications

Topical medications

Erythromycin, clindamycin

Clindamycin, erythromycin, azelaic acid

Spironolactone, trimethoprim,

Adapalene, tretinoin, benzoyl peroxide, nicotinamidea,

salicylic acid

Tetracycline, doxycycline,



Table 3 Summary of case reports of birth defects associated with topical retinoid use
Case report

Topical agent used

Duration of use


Gestation at

Congenital defect reported

Camera and
Pregliasco [23]

Tretinoin 0.05 % cream

Before conception and

up to 11 weeks

Not stated

41 weeks

Hypoplastic ear, atresia of the

external auditory meatus

Lipson et al. [24]

Tretinoin 0.05 % alcoholbased topical application

Before conception and

up to 5 weeks gestation

Not stated

Not stated

Supraumbilical hernia,
diaphragmatic hemia, pericardial
defect, dextroposition of the
heart, right upper limb defect

Selcen et al. [25]

Tretinoin 0.025 % topical


Before conception and

up to 2 to 3 months

Not stated

41 weeks

Absence of ear and external

auditory canal

NavarreBelhassen et al.

Tretinoin 0.05 % alcoholbased topical application

Before conception and

up to 2 months

Not stated

40 weeks

Coarctation of the aorta,

hypoplastic left hand,
hypertelorism, small ear canals

Autret et al. [27]

Adapalene 0.1 % gel

Before conception and

up to 13 weeks

0.3 mg

at 22 weeks

Anophthalmia agenesis of the

optic chiasma

topical therapies have been developed for use in acne.

These have not been included in this review as we have
focused on the individual active ingredients and their safety
The absorption of topical therapies is influenced by
many factors including the following:

Amount of agent applied

Surface area of application
Length of application time
Frequency of application
Application to broken skin/erosions
Choice of vehicle used
Thickness of stratum corneum

2.1 Benzoyl Peroxide

Benzoyl peroxide is a commonly used acne treatment that
comes in a variety of strengths (2.510 %) and formulations (cream, gel, wash, aqueous gel). Benzoyl peroxide
works as a keratolytic, comedolytic, and anti-inflammatory
agent. Its antimicrobial activity is based on generating
highly reactive oxygen radicals, an effect to which Propionibacterium acnes has not developed resistance [20].

There is some evidence that benzoyl peroxide is

absorbed systemically and, in an animal model, the
absorbed benzoyl peroxide was excreted rapidly in urine as
benzoic acid [21], which was unaffected by the concentration of benzoyl peroxide used. This rapid renal clearance
prevents hepatic conjugation to hippuric acid [22].
There are no studies looking at the use of topical benzoyl peroxide in pregnancy and so it has been assigned
FDA pregnancy category C. As only about 5 % of the
benzoyl peroxide applied topically was found to be
absorbed in one study, the potential risk during pregnancy
is low [22].
2.2 Topical Retinoids
There are four topical retinoids used in the treatment of
acne: tretinoin, isotretinoin, tazarotene, and adapalene.
These are often used as the first-line treatment for mild to
moderate acne, especially when mainly comedonal.
There have been some case reports of birth defects in
babies who had prenatal exposure to topical retinoids.
There have been four case reports of congenital birth
defects after the use of topical tretinoin in early pregnancy
(see Table 3) [2326]. There has also been one case report


of anophthalmia that was thought to be associated with

topical adapalene use [27].
These reports were particularly concerning as the birth
defects were similar to those whose mothers had taken oral
isotretinoin [28]. However, a subsequent case control study
did not show an increased risk for major congenital defects
[29]. Most recently, a prospective observational study of
235 women exposed to a topical retinoid during their first
trimester were compared with 444 women in the control
group (matched for maternal and gestational age). No
significant differences in major or minor birth defects were
detected between the two groups. However, this sample
size could not exclude infrequent outcomes or a smaller
effect than a two to three times increase in risk [30].
A formal consensus on the safety of topical retinoids in
pregnancy is lacking [31] and because the manufacturers
advise that they should not be used during pregnancy, this
treatment cannot be recommended at present.

F. M. Meredith, A. D. Ormerod

However, salicylates do occur naturally in the diet and

subsequent cohort studies showed no increase in risk [36].
Salicylism has occurred using methyl salicylate ointments
and high concentrations of salicylic acid on widespread
areas of hyperkeratotic skin, but there are no known cases
resulting from salicylic acid acne products [32].
2.6 Nicotinamide
Nicotinamide is the amide of nicotinic acid (vitamin B3).
Again, it is a normal dietary constituent present in the
diet. Regarding systemic absorption, just over 10 % of
the total applied dose of nicotinamide was absorbed over
5 days in a human study [37]. Topical nicotinamide use
is not restricted during pregnancy (although the manufacturers advise caution in the first trimester), but oral
nicotinamide changes from class A to pregnancy class C
if the dose exceeds the recommended daily allowance

2.3 Topical Antibiotics

2.7 Abrasive Agents
Because of the increasing problem of antibiotic resistance,
monotherapy with topical antibiotics is generally not recommended [9]. The main topical antibiotics used are
clindamycin and erythromycin.
Clindamycin is a semi-synthetic derivative of lincomycin that inhibits bacterial protein synthesis by attaching to
the bacterial ribosome [32]. It is available in a gel, lotion,
or topical solution [33]. It has been assigned FDA pregnancy category B, as animal studies have failed to reveal
evidence of teratogenicity when high doses of clindamycin
are given systemically.
Erythromycin is a macrolide antibiotic available as a
gel, solution, or ointment. Percutaneous absorption of
erythromycin is very low [32]. Oral and topical erythromycin formulations are both FDA category B, as animal
studies have shown no evidence of teratogenicity [32].
2.4 Azelaic Acid
Azelaic acid has antimicrobial and anticomedonal properties [8]. This is a naturally occurring dicarboxylic acid
found in wholegrain cereals such as wheat, rye, and barley
[34]. One study found that after application of the 20 %
cream formulation, 3.6 % of the dermal applied dose was
percutaneously absorbed [35]. It is categorized as FDA
pregnancy class B, as animal studies have shown no teratogenicity but human data are not available.
2.5 Salicylic Acid
Salicylates were thought to be teratogenic because of animal data showing an increase in cardiac malformations.

Although many cosmetic face washes and scrubs contain

abrasive agents, these are not considered beneficial in acne

3 Oral Preparations
3.1 Oral Antibiotics
Outside of pregnancy, oral antibiotics are commonly prescribed as a second-line therapy for acne. The most commonly prescribed are tetracyclines: doxycycline,
oxytetracycline, lymecycline (not available in the USA),
minocycline, and tetracycline.
There has been increasing concern about the risk of
antibiotic resistance [38] and the use of oral and topical
antibiotics concurrently (unless chemically similar agents).
Antibiotic resistance can develop within 12 weeks [39] and
is thought to impede therapeutic response.
Penicillins, erythromycin, and cephalosporins are
thought to have the best safety profile in pregnancy [40],
with erythromycin the oral antibiotic most commonly used
for acne in pregnancy.
3.1.1 Tetracyclines
Tetracyclines should not be used during pregnancy, as use
in the second and third trimester can cause discoloration of
teeth and bones. Fatty liver of pregnancy in the third trimester has also been attributed to tetracycline ingestion
[41]. There is no firm evidence that first-trimester use is

Management of Acne Vulgaris in Pregnancy

associated with major birth defects but their use is not

recommended at any stage of pregnancy.
3.1.2 Trimethoprim
Trimethoprim is a dihydrofolate reductase inhibitor that
reduces the conversion of folate to its more active metabolites. A retrospective case-control study found that in
early pregnancy, trimethoprim may increase the risk of
cardiovascular defects, oral clefts, and urinary tract defects,
particularly among the infants of women who do not use a
multivitamin containing folic acid [40].
3.1.3 Clindamycin
Oral clindamycin has been shown to be effective in the
management of acne [42] but is known to be a cause of
antibiotic-associated diarrhea [43] and colitis [33]. Clindamycin use also increases the risk of Clostridium difficile
infection, resulting in a widespread restriction of clindamycin prescribing [44]. Regarding safety in pregnancy, of
647 first-trimester exposures to clindamycin, no increased
risk of a birth defect was detected [45].
3.1.4 Erythromycin
Erythromycin is the oral antibiotic of choice for acne
during pregnancy [36]. It is more commonly used in
pregnancy to treat other infections, allowing retrospective
analysis of pregnancy outcomes to be studied [46]. As
previously mentioned, oral erythromycin is FDA pregnancy category B. There is increasing bacterial resistance
to erythromycin and so it should be combined with a topical preparation where possible [47]. Erythromycin estolate
is the preparation that has been most noted to cause hepatotoxicity in pregnancy and it is probably best avoided,
but this can rarely happen with other esters [48].


improve the appearance of acne [52]. Antiandrogens such

as spironolactone are contraindicated during pregnancy
because of the theoretical risk of feminization of male
fetuses [53].
Co-cyprindiol 2000/35 (cyproterone acetate 2 mg, ethinylestradiol 35 lg), also known as Dianette (Bayer
Schering Pharma, UK), is not available in the USA but is
licensed in the UK for the treatment of acne that has not
responded to prolonged oral antibacterials [33]. This is also
contraindicated in pregnancy.
3.3 Oral Retinoids
The use of oral retinoids in pregnancy is absolutely contraindicated [54]. This is because of the severe teratogenicity associated with retinoids, namely craniofacial,
cardiac, and thymic malformations [55]. As a result of
these teratogenic effects, the manufacturers of oral isotretinoin have developed pregnancy prevention programs
whereby the use of at least one but preferably two methods
of contraception is recommended [54]. Currently, enrolling
on the pregnancy prevention program is compulsory in the
USA, and in the UK exemptions are only made in exceptional circumstances. Women should be aware that they
should not become pregnant 1 month before, during, or for
1 month after taking isotretinoin.
3.4 Zinc
During the literature review, a paper was found that had
surveyed French dermatologists and found that around
10,000 pregnant women and 2,000 breast-feeding women
were treated for acne using zinc gluconate with only four
serious adverse events reported [56]. In the S3 European
acne guidelines, oral zinc can be considered for the treatment of mild to moderate acne based on a low strength of
recommendation [9]. Topical zinc alone is ineffective for
acne treatment [8].

3.1.5 Azithromycin
3.5 Oral Corticosteroids
Azithromycin is an azalide antibiotic derived from erythromycin [45]. It has been used in the treatment of acne and has
been found to be as effective as doxycycline [49]. Animal
studies have shown that azithromycin crosses the placenta but
there are no adequate and well-controlled studies in pregnant
women. As such, the UK Medicines and Healthcare products
Regulatory Agency (MHRA) have recommended it only be
used if adequate alternatives are not available [50].
3.2 Anti-Androgens
Spironolactone is not licensed for use in acne, although it
has been found to decrease sebum secretion [51] and

In the American Academy of Dermatology guidelines,

expert opinion states that short courses of higher dose oral
corticosteroids may be beneficial in patients with highly
inflammatory disease [8]. The dose range to be used is not
specified. It is well documented that corticosteroid use can
induce acneiform lesions [57], but 0.51 mg/kg/day courses of oral corticosteroids can be used in conjunction with
oral isotretinoin to treat acne fulminans [58]. Prednisolone
has been given FDA pregnancy category C (D if in the first
trimester). Corticosteroids have caused oral clefts in animal
studies [36]. Prospective cohort studies in humans have not
shown a teratogenic effect, but have had limited power


[59]. Prolonged or repeated use of corticosteroids in

pregnancy can increase the risk of intrauterine growth
restriction [60]. It is also important to note that dexamethasone and betamethasone readily cross the placenta
compared with prednisolone where 88 % is inactivated
crossing the placenta [60]. One study of 311 first-trimester
exposures to corticosteroids found lower median birth
weight (3,080 vs. 3,290 g; P \ 0.001) and earlier median
gestational age (39 vs. 40 weeks; P \ 0.001) [59].

F. M. Meredith, A. D. Ormerod

the course of the acne but may improve the appearance of

the skin [8]. Hyfrecation of comedones can also be an
effective physical therapy [65].
4.3 Dietary Restriction
Dietary restriction has not been shown to be of benefit in
the treatment of acne [2, 8]. Dietary manipulation should
not be encouraged during pregnancy.
4.4 Other Therapies

4 Non-Pharmacologic Treatment Options

There are many other treatment modalities that have been
used to treat acne. Some are used to treat the inflammatory
lesions; others are aimed at improving any scarring or postinflammatory hyperpigmentation. Cosmetic treatments for
acne scarring are not included in this review and elective
procedures are probably best delayed until after delivery.
4.1 Laser and Blue-Light Treatments
There have been various devices trialed for use in inflammatory acne and for treating scarring [61]. Light therapies
for acne are thought to kill P. acnes and shrink sebaceous
glands, reducing sebum output [62]. In the most recent
European guidelines, a low strength of recommendation was
made for the treatment of mild to moderate papulopustular
acne with blue-light monotherapy. No recommendation was
made for or against treatment with red light, intense-pulsed
light, laser or photodynamic therapy for the same grade of
acne [9]. There are limited data on these therapies and
uncertainty regarding the optimal dosing strategy.
Often maintenance therapy is required with light-based
therapies, but particularly as they carry no risk to the fetus
they represent an attractive option for treatment in pregnancy. The exception is photodynamic therapy where
neither aminolevulinic acid nor methyl aminolevulinate has
been studied for use in pregnant women and should be
avoided [63].
Narrow-band ultraviolet B phototherapy is used for
other indications during pregnancy and there is a single
case report of it being used successfully to treat acne during
pregnancy [64]; however, previous studies have shown
poor long-term efficacy [61].
There are some studies using laser sources to treat noninflammatory acne lesions but the published evidence is
still scarce in this area [9].
4.2 Comedo Extractors
Despite widespread use, comedo extractors have very little
evidence to support their use. They are not thought to alter

Many herbal agents have been used in the treatment of acne

vulgaris but there are few data on their safety and efficacy
available [8] and therefore their use cannot be recommended in pregnancy.

5 Conclusions
There are a limited number of options available for the safe
management of acne in pregnancy. Isotretinoin, which is
the mainstay of treatment for severe and nodulocystic acne,
is absolutely contraindicated in pregnancy.
The options for oral antibiotics are also limited with
erythromycin being the safest option available. Unfortunately, this is also the least effective oral antibiotic to be
used and evidence supporting its efficacy in acne is poor
Where possible, acne treatments in pregnancy should be
limited to topical treatments [41]. They have the best safety
profile and minimize the levels of systemic absorption, and
therefore have the least risk of fetal exposure. If these are
applied properly with a strong emphasis on adherence,
excellent results can be achieved. Previous reviews have
recommended topical erythromycin, clindamycin, and
benzoyl peroxide as the agents of choice [36, 41, 66, 67].
The purpose of this review is not to create a guideline
but to collate the available data on acne therapies in
pregnancy to help decision making for patients and
clinicians. To this end, we have tried to summarize our
findings in Table 4 and rank therapies based on their
safety profile. With more severe cases of acne, topical
treatments still have an important role in improving
symptoms and minimizing any ongoing scarring. These
may be safely supported by physical treatments including light-based therapies but not photodynamic therapy.
When systemic therapy is required, discussion between
the physician and patient is required to explain potential
risks, benefits, and paucity of evidence of the available
options including oral erythromycin, oral corticosteroids, and zinc as possible choices to augment topical

Management of Acne Vulgaris in Pregnancy

Table 4 Summary of authors
views on acne therapies in

In cases of acne fulminans,

after first trimester



Favorable safety profile

Benzoyl peroxide, azelaic acid, nicotinamide, erythromycin,

clindamycin, zinc, prednisolonea

Safety concerns/inadequate data

Topical retinoids, salicylates, azithromycin


Tetracyclines, oral retinoids, trimethoprim, anti-androgens

6 Useful Resources


cs/WomensHealthResearch/ucm134848.htm Information aimed at helping pregnant women make informed
choices about medicine use during their pregnancy.
The Organization of Teratology Information Specialists
(ORTIS) provides education and support to teratology services in North
America. It also provides many links to relevant government and professional bodies.
UK Teratology Information Service (UKTIS) http:// collects data on all aspects of the toxicity of drugs and chemicals in pregnancy and has
helpful summary sheets available online for many
topical and oral medications.
The UK MHRA is the government organization that collects, monitors, and reports
safety data on medications in the UK. They produce
drug analysis prints of suspected adverse drug reactions
and side effects that have been reported to them.
The electronic Medicines Compendium (eMC) http:// is a useful resource that contains patient information leaflets and summaries of
product characteristics

Acknowledgments Both authors have no relevant conflicts of

interest. FMM researched and drafted the initial document, which was
then reviewed and edited by ADO.

1. Smithard A, Glazebrook C, Williams HC. Acne prevalence,
knowledge about acne and psychological morbidity in mid-adolescence: a community-based study. Br J Dermatol. 2001;145:
2. Bhate K, Williams HC. Epidemiology of acne vulgaris. Br J
Dermatol. 2013;168:47485.
3. Williams C, Layton AM. Persistent acne in women: implications
for the patient and for therapy. Am J Clin Dermatol. 2006;7(5):
4. Shafer T, Nienhaus A, Vieluf D, et al. Epidemiology of acne in
the general population: the risk of smoking. Br J Dermatol.
5. Burton JL, Cunliffe WJ, Stafford I, et al. The prevalence of acne
vulgaris in adolescence. Br J Dermatol. 1971;85:11926.

6. US Food and Drug Administration. List of pregnancy exposure

registries [online]. (Accessed 12 Dec
7. FDA Consumer Health Information. Pregnant women to benefit
from better information [online].
ForConsumers/ConsumerUpdates/UCM143746.pdf (Accessed 12
Dec 2012).
8. Strauss JS, Krowchuk DP, Leyden JJ, et al. Guidelines of care for
acne vulgaris management. J Am Acad Dermatol. 2007;56:65163.
9. Nast A, Dreno B, Bettoli V, et al. European evidence-based (S3)
guidelines for the treatment of acne. J Eur Acad Dermatol
Venereol. 2012;26:129.
10. Elling SV, Powell FC. Physiological changes in the skin during
pregnancy. Clin Dermatol. 1997;15:3543.
11. Burton JL, Cunliffe WJ, Millar DG, Shuster S. Effect of pregnancy on sebum excretion. BMJ. 1970;2:76971.
12. Muzaffar F, Hussain I, Haroon TS. Physiologic skin changes
during pregnancy: a study of 140 cases. Int J Dermatol.
13. Dawes M, Chowienczyk PJ. Drugs in pregnancy: pharmacokinetics
in pregnancy. Best Pract Res Clin Obstet Gynaecol. 2001;15:81926.
14. Loebstein R, Lalkin A, Koren G. Pharmacokinetic changes during pregnancy and their clinical relevance. Clin Pharmacokinet.
15. Boothby LA, Doering PL. FDA labeling system for drugs in
pregnancy. Ann Pharmacother. 2001;35:14859.
16. Public Affairs Committee of the Teratology Society. Teratology
Public Affairs Committee position paper: pregnancy labeling for
prescription drugs: ten years later. Birth Defects Res Part A Clin
Mol Teratol. 2007;79:62730.
17. Addis A, Sharabi S, Bonati M. Risk classification systems for
drug use during pregnancy: are they a reliable source of information? Drug Saf. 2000;23(3):24553.
18. US Food and Drug administration. Pregnancy and lactation
labeling [online].
(Accessed 12 Dec 2012).
19. MIMS USA drug information system [online]: http://www.mims.
com/USA/Viewer/Html/PregDef.htm (Accessed 12 Dec 2012).
20. Tanghetti E. The evolution of benzoyl peroxide therapy. Cutis.
2008;82(5 Suppl.):511.
21. Yeung D, Nacht S, Bucks D, Maibach HI. Benzoyl peroxide:
percutaneous penetration and metabolic disposition. II. Effect of
concentration. J Am Acad Dermatol. 1983;9:9204.
22. Nacht S, Yeung D, Beasley JN, et al. Benzoyl peroxide: percutaneous penetration and metabolic disposition. J Am Acad Dermatol. 1981;4(1):317.
23. Camera G, Pregliasco P. Ear malformation in baby born to
mother using tretinoin cream. Lancet. 1992;339:687.
24. Lipson AH, Collins C, Webster W. Multiple congenital defects
associated with maternal use of topical tretinoin. Lancet.
25. Selcen D, Seidman S, Nigro MA. Otocerebral anomalies associated with topical tretinoin use. Brain Dev. 2000;22:21820.

26. Navarre-Belhassen C, Blanchet P, Hillaire-Buys D, et al. Multiple
congenital malformations associated with topical tretinoin. Ann
Pharmacother. 1998;32:5056.
27. Autret E, Berjot M, Jonville-Bera A-P, et al. Anophthalmia and
agenesis of optic chiasma associated with adapalene gel in early
pregnancy. Lancet. 1997;350:339.
28. Organisation of Teratology Information specialists. Tretinoin
(Retin-A) and pregnancy [online]. http://www.otispregnancy.
org/files/tretinoin.pdf (Accessed 12 Dec 2012).
29. Jick SS, Terris BZ, Jick H. First trimester topical tretinoin and
congenital disorders. Lancet. 1993;341:11812.
30. Panchaud P, Csajka C, Merlob P, et al. Pregnancy outcome following exposure to topical retinoids: a multicentre prospective
study. J Clin Pharmacol. 2012;52:184451.
31. Van Hoogdalem EJ. Transdermal absorption of topical anti-acne
agents in man; review of clinical pharmacokinetic data. J Eur
Acad Dermatol Venereol. 1998;11 Suppl. 1:S139.
32. Akhavan A, Bershad S. Topical acne drugs: review of clinical
properties, systemic exposure and safety. Am J Clin Dermatol.
33. Joint Formulary Committee. British National Formulary. 64th ed.
London: BMJ Group and Pharmaceutical Press; 2012.
34. Frampton JE, Wagstaff AJ. Azelaic acid 15% gel in treatment of
papulopustular rosacea. Am J Clin Dermatol. 2004;5:5764.
35. Tauber U, Weiss C, Matthes H. Percutaneous absorption of
azelaic acid in humans. Exp Dermatol. 1992;1:1769.
36. Koren G, Pastuszak A, Ito S. Drugs in pregnancy. N Engl J Med.
37. Feldmann RJ, Maibach HI. Absorption of organic compounds
through the skin in man. J Invest Dermatol. 1970;54:399404.
38. Dreno B, Bettoli V, Ochsendorf F, et al. European recommendations on the use of oral antibiotics for acne. Eur J Dermatol.
39. Harkaway KS, McGinley KJ, Foglia AN, et al. Antibiotic resistance patterns in coagulase-negative staphylococci after treatment
with topical erythromycin, benzoyl peroxide, and combination
therapy. Br J Dermatol. 1992;126:58690.
40. Hernandez S, Werler MM, Walker AM, et al. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J
Med. 2000;343:160814.
41. Hale EK, Pomeranz MK. Dermatological agents during pregnancy and lactation: an update and clinical review. Int J Dermatol. 2002;41:197203.
42. Cunliffe WJ, Cotterill JA, Williamson B. The effect of clindamycin in acne: a clinical and laboratory investigation. Br J
Dermatol. 1972;87:3741.
43. Tan SG, Cunliffe WJ. The unwanted effects of clindamycin in
acne. Br J Dermatol. 1976;94:3135.
44. Owens RC, Donskey CJ, Gayens RP, et al. Antimicrobial-associated risk factors for Clostridium difficile infection. Clin Infect
Dis. 2008;46(Suppl. 1):S1931.
45. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and
lactation: a reference guide to fetal and neonatal risk. 8th ed.
Philadelphia: Lippincott Williams & Wilkins; 2008.
46. Romren M, Lindbk M, Nordeng H. Pregnancy outcome after
gestational exposure to erythromycin: a population-based register
study from Norway. Br J Clin Pharmacol. 2012;74:105362.
47. Thiboutot D, Gollnick H, Bettoli V, et al. New insights into the
management of acne: an update from the Global Alliance to

F. M. Meredith, A. D. Ormerod














improve outcomes in acne group. J Am Acad Dermatol.

2009;60(5 Suppl.):S150.
Sweetman SC, et al. Martindale: the complete drug reference.
34th ed. London: Pharmaceutical Press; 2005.
Kus S, Yucelten D, Aytug A. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of acne vulgaris. Clin
Exp Dermatol. 2004;30:21520.
UK Medicines and Healthcare products Regulatory Agency
(MHRA) azithromycin UKPAR (UK Public Assessment Reports
for medicines). (Accessed 4 July 2013).
Goodfellow A, Alaghband-Zadeh J, Carter G, et al. Oral spironolactone improves acne vulgaris and reduces sebum excretion.
Br J Dermatol. 1984;111:20914.
Muhlemann MF, Carter GD, Cream JJ, Wise P. Oral spironolactone: an effective treatment for acne vulgaris in women. Br J
Dermatol. 1986;115:22732.
Jaussan V, Lemarchand-Beraud T, Gomez F. Modifications of the
gonadal function in the adult rat after fetal exposure to spironolactone. Biol Reprod. 1985;32:105161.
Goodfield MJ, Cox NH, Bowser A, et al. Advice on the safe
introduction and continued use of isotretinoin in acne in the U.K.:
2010. Br J Dermatol. 2010;162:11729.
Lammer EJ, Chen DT, Hoar RM, et al. Retinoic acid embryopathy. N Engl J Med. 1985;313:83741.
Dreno B, Blouin E. Acne, pregnant women and zinc salts: a
literature review. Ann Dermatol Venereol. 2008;135(1):2733.
Du-Thanh A, Klugr N, Bensalleh H, Guillot B. Drug-induced
acneiform eruption. Am J Clin Dermatol. 2011;12:23345.
Seukeran DC, Cunliffe WJ. The treatment of acne fulminans: a
review of 25 cases. Br J Dermatol. 1999;141:3079.
Gur C, Diav-Citrin O, Shechtman S, et al. Pregnancy outcome
after first trimester exposure to corticosteroids: a prospective
controlled study. Reprod Toxicol. 2004;18:93101.
Committee on safety of medicines/medicines control agency.
Systemic corticosteroids in pregnancy and lactation. Curr Probl.
websiteresources/con2023392.pdf (Accessed 28 June 2013).
Ross EV. Optical treatments for acne. Dermatol Ther. 2005;18:
Car J, Car M, Hamilton F, et al. Light therapies for acne (intervention protocol). Cochrane Database Syst Rev. 2009;(3):
Sakamoto FH, Torezan L, Anderson R. Photodynamic therapy for
acne vulgaris: a critical review from basics to clinical practice:
part II. Understanding parameters for acne treatment with photodynamic therapy. J Am Acad Dermatol. 2010;63:195211.
Zeichner JA. Narrowband UV-B phototherapy for the treatment
of acne vulgaris during pregnancy. Arch Dermatol. 2011;147:
Cunliffe WJ, Holland DB, Clark SM, Stables GI. Comedogenesis: some new aetiological, clinical and therapeutic strategies. Br
J Dermatol. 2000;142:108491.
Zip C. A practical guide to dermatological drug use in pregnancy.
Skin Ther Lett. 2006;11:14.
Crider KS, Cleves MA, Reefhuis J, et al. Antibacterial medication
use during pregnancy and risk of birth defects. Arch Pediatr
Adolesc Med. 2009;163(11):97885.

Copyright of American Journal of Clinical Dermatology is the property of Springer Science &
Business Media B.V. and its content may not be copied or emailed to multiple sites or posted
to a listserv without the copyright holder's express written permission. However, users may
print, download, or email articles for individual use.