Acne & Pregnancy
Elevated hormone levels during pregnancy usually bring about a number of skin changes. Acne being one of the most troublesome skin conditions during this time. Acne treatment in non-pregnant women is usually through prescription medications such as Retin-A, antibiotics such as Tetracycline, Erythromycin and Oxycycline and Accutane. However, use of many of these medications is not appropriate during pregnancy or in women trying to become pregnant and must be extensively discussed with your obstetrician or primary care physician. During pregnancy, acne can both clear or get worse. In early pregnancy, acne often gets somewhat worse, but as the pregnancy progresses, acne often improves, possibly due to the increased levels of estrogen.
When opting for over-the-counter medicated acne products and treatments, it is strongly recommended that you first consult with your health care physician. There are some products that contain benzoyl peroxide, which has been recommended safe for use during pregnancy. However, there are other over-the-counter medications that should be avoided such as products containing salicylic acids. Consulting your health care provider before taking ANY medications during pregnancy, whether prescription or over-the-counter is very important.
Using Acne Products While Pregnant
Isotretinoin or Accutane: This is a prescription medication that is taken orally to treat acne. According to the Organization of Teratology Information Services (OTIS), approximately 25-35% of infants born to women exposed to Accutane during the first trimester of pregnancy showed a pattern of birth defects. This pattern includes craniofacial defects, heart defects, and central nervous system defects. There also is an increased risk of miscarriage and infant death associated with use of Accutane during pregnancy. It is usually safe to use Accutane when you are not pregnant and have discussed the essential precautions with your physician.
- If you are in your childbearing years you must use two forms of birth control, beginning one month prior to starting Accutane through one month after stopping Accutane. It is contraindicated during breastfeeding and should be taken. You must be counseled about the possible ways that your chosen birth control may fail.
- One week prior to taking Accutane you must have a negative pregnancy test.
- Accutane should be started on the 2nd or 3rd day after the subsequent normal menstrual cycle.
Tretinoin or Retin-A: Retin-A is a prescription cream that is applied to the skin to treat acne. The generic name for Retin-A is tretinoin. According to OTIS, less than 10% of Retin-A passes into the mother's blood stream and less than that reaches the baby. Even with these findings, Retin-A still carries warnings of use by women who are pregnant or contemplating pregnancy. You should always discuss treatment with your physician.
Tetracycline/Oxycycline: Tetracycline is an antibiotic taken orally to treat acne and respiratory infections. Tetracycline should not be taken during pregnancy unless prescribed by your physician. The American Academy of Pediatrics has approved tetracycline safe for use during breastfeeding. Two retrospective studies found no increase in the incidence of major malformations when women were exposed to tetracycline in the first trimester (Heinonen et al., 1977; Briggs, 1998). However, discoloration of deciduous teeth and the crowns of permanent teeth were seen in children who were exposed to tetracycline after the fourth month of gestation. Studies performed by Cohlan et al. (1961), Kline et al. (1964) and Kutscher et al. (1966) established that infants exposed to tetracycline in utero after the fourth month of gestation may have discoloration of deciduous ("baby") teeth, cavities, and enamel hypoplasia in their teeth. It is believed that tetracycline causes dental discoloration and bone depression because it acts on the calcification process in development. The critical period for calcification begins at four months' gestation and ends twelve months post-partum. Therefore, tetracyline should be avoided after the sixteenth week of gestation and throughout lactation. The degree of dental staining appears to proportional to the dose of the medication (Egerman et al., 1992). Cohlan et al. (1961) also found that tetracycline caused long bone growth depression of 40% which normalized when the use of the medication was suspended. Doxycycline and minocycline, two medications structurally-related to tetracycline, are also used to treat acne. These medications have not been as well-studied as tetracycline; it is, however, generally assumed that doxycycline and minocycline similarly affect the fetal calcification process. Therefore, these medications should also be avoided after the first trimester of pregnancy through the breastfeeding period.
Hormone therapy: The "female" hormone, estrogen, and the anti-androgens, flutamide and spironolactone, are sometimes used to treat acne in women. These should not be taken while a woman is pregnant. Flutamide and spironolactone have been known to cause birth defects. It is not known if these medications can be passed along when a woman is breast feeding so the medications must also not be used if a woman chooses to breast feed.
Hydrocortisone (w/ benzoyl peroxide, Vanoxide-HC): Hydrocortisone is a corticosteroid used topically to treat acne and other skin conditions. There have been no studies on reproductive effects to topical exposures to hydrocortisone specifically, and as such its risk in pregnancy is undetermined.
Benzoyl Peroxide (Benzac, Benzamycin, Beroxyl, Desquam, Triaz, Vanoxide): Benzoyl peroxide is a topical treatment for acne that has antibacterial effects and helps in skin peeling. Approximately 5% of each topical dose is absorbed systemically. There are no mammalian reproductive studies on benzoyl peroxide, and therefore its potential teratogenic risk is undetermined. However, benzoyl peroxide is commonly used, and there are no case reports about benzoyl peroxide and birth defects in the literature. This, combined with its topical exposure, provides some reassurance that the risk of malformations is likely to be low. But, it is still recommended that the use of this should be discussed with your physician prior to use.
Salicylic Acid: Salicylic acid is used to treat acne and other dermatological conditions. There is not much medical literature specifically looking at topical salicylic acid in pregnancy. Oral salicylic acid (aspirin) has not been associated with an increase in malformations if used during the first trimester, but use in late in pregnancy has been associated with bleeding, especially intracranial bleeding (Rumack et al., 1981). The risks of aspirin late in pregnancy are probably not relevant for a topical exposure to salicylic acid, even late in the pregnancy, because of its low systemic levels. Topical salicylic acid is common in many over-the-counter dermatological agents, and the lack of adverse reports suggests a low cancer potential.
Erythromycin (A/T/S 2% acne gel, Benzamycin, Emgel, Erycette, T-Stat, Theramycin): Erythromycin is an antibiotic that is commonly prescribed in pregnancy. Although often taken orally to treat infection, it is also used topically for acne. Erythromycin does cross the placenta in a small dose; the fetal blood concentration is only 2-10% of the maternal serum concentration, and the medication is quickly metabolized by the body. Takaya et al. (1965) found no increased malformations in mice exposed to 1-20 times the human dose. Human studies on erythromycin have all examined oral exposures. Retrospective studies of 79 and 6972 women exposed in first trimester had no significant increase in birth defects (Heinonen et al., 1977; Briggs, 1998). Jick et al. (1981) examined the prescription records of women exposed to erythromycin during the first trimester and also found no increase in birth defects (n=100-200). Because of these studies and the fact that this medication is commonly prescribed, it is generally assumed that topical erythromycin does not pose a significant increased risk for birth defects.
Clindamycin (Cleocin): Clindamycin is an antibiotic related to erythromycin and available both orally and topically for the treatment of acne. It has been studied in both mice and rats at doses up to 180 mg/kg/day without teratogenic effects (Weinstein et al., 1976; Philipson et al., 1976). The retrospective Michigan Medicaid study identified 647 women exposed to clindamycin in the first trimester (both oral and topical exposures) and did not note an increased risk for major malformations. Furthermore, a study of 104 women exposed to clindamycin in the second and third trimesters did not suggest an increased risk for prematurity or placental complications (McCormack et al., 1987). This medication is unlikely to significantly increase the risk for birth defects in either its oral or topical form.
Sodium Sulfacetamide (Klaron, Novacet, Sebizon, Sulfaset): Sodium sulfacetamide is a topical anti-infective medication used to treat acne and seborrheic skin conditions. It belongs to the class of medications termed sulfonamides, and most reproductive studies examine sulfonamides as a class and in oral dosages, making it difficult to extrapolate the potential risk for a topical medication such as sulfacetamide. The maternal use of sulfonamides near delivery can lead to newborn toxicity, resulting in anemia and jaundice and, theoretically, kernicterus, although this has yet to be documented in the literature. (Briggs, 1998). There have been two large retrospective studies of sulfonamide exposure, which involved 1445 and 3465 women exposed in the first trimester; neither study found an increased risk for malformations from the class in general (Heinonen et al., 1977; Briggs, 1998). In contrast, other case controlled studies raised concerns about sulfonamide use in pregnancy. A 1971 case-control study by Nelson et al. determined the pregnancy exposures of 1369 patients, 468 of whom had babies with congenital malformations. They observed that significantly more mothers of the babies with birth defects took sulfonamides than the control mothers (Nelson et al., 1971). Saxon et al. (1975) looked retrospectively at 599 children born with oral clefts. The mothers of children with malformations in addition to the oral clefts were more likely to have taken sulfonamides than mothers of children with isolated oral clefts. Because topical sulfacetamide has never been specifically studied to determine its potential teratogenic risk, one cannot definitively conclude that it does not cause birth defects. However, because it is topical and, for the most part, sulfonamides as a class do not appear to significantly increase the risk for birth defects, it is unlikely that topical sulfacetamide causes a significantly increased risk for malformations. Breastfeeding while using sulfonamides is probably not a risk to a healthy infant. At most 1-2% of a maternal, oral dose of sulfonamides enters the breast milk (Adair, 1938; Hac, 1939). However, sulfonamides can potentially cause anemia and jaundice in stressed, premature or hyperbilirubinemic infants. In addition, if an infant has G-6-PD deficiency breastfeeding should be avoided while taking sulfonamides, as sulfonamides act as oxidative stressors and can result in a hemolytic crisis.
Adapalene (Differin Gel): Adapalene is a retinoid used in a topical gel form for the treatment of acne. As such, there are theoretical risks for retinoid embryopathy. However, the manufacturer reports that only trace amounts of adapalene are absorbed from the skin (trace is defined as less than 0.25 ng/ml). The manufacturer's studies on pregnant rats and rabbits using doses 120-150 times the maximum human topical dose did not show an increased risk of adverse outcome or malformations. There has been one human case report of adapalene use during weeks 4-13 of pregnancy; the fetus had IUGR, anophthalmia and agenesis of the optic chiasm, and the pregnancy was aborted at 13 weeks (Autret et al., 1997). The anomalies seen in this pregnancy are not typical of those seen with other retinoid exposures. In addition, as with any case report, the malformations could be coincidental and unrelated to the adapalene. There have not been any other human studies or case reports to date. The overall risk of adapalene is undetermined because there have not been any human studies. However, because only trace amounts of the gel are absorbed into the skin, it is unlikely that doses large enough to induce malformations could reach a fetus.
Azelaic Acid (Azelex): Azelaic acid is a topical cream for acne. The manufacturer's studies in animals do not show an increase in malformations at doses much higher than the maximum human dose. There have not been any human reproductive studies to date. While it is reassuring that animal studies do not show teratogenicity and that the fetal dose is small because the medication is topical, the risk of azelaic acid is undetermined because there have been no human studies.
Summary:
Acne medications may present a range of risks issues during pregnancy. Isotretinoin (Accutane) should not be taken during pregnancy due to its well established risk of causing cancer and birth defects. Also, tetracycline and its derivatives should not be used after 16 weeks gestation due to its effects on calcium-containing tissue, particularly teeth. The risks of other medications such as tretinoin are less clear cut. Some commonly used preparations, with benzoyl peroxide, do not appear to pose as significant a risk for birth defects. There are a wide variety of medications available for the treatment of acne, many of which pose a minimal risk if applied topically during pregnancy. The use of any of these should be thoroughly discussed with your physician and health monitoring during their use should be regular and essential.
According to a paper published in the Annals of Dermatologic Venereology in Jan of 2008 (Jan;135(1):27-33. Epub 2008 Jan 18)titled "Acne, pregnant women and zinc salts: a literature review" [Article in French] by B. Drno and E. Blouin, Zinc plays a key role in our body's physiology by modulating activities of many enzymes. Zinc requirements increase during pregnancy, mainly because of its utilization during embryogenesis and fetal development. These authors showed in literature review that use of zinc salts in pregnant women is beneficial in those with zinc deficiency but that it has no harmful effects in those without zinc deficiency.