A woman's body undergoes tremendous changes during pregnancy, many of which are cutaneous (i.e., relating to the skin) in nature. One such change could be pigmentation, wherein certain parts of the skin grow darker in colour due to more melanin being produced. Physiological changes in melanin pigment production, due to oestrogen stimulation and elevated levels of melanocyte-stimulating hormone, are responsible for the common pregnancy-induced pigmentary phenomena (Friedman et al, 2019), which include linea nigra, an increase in pigmentation, and melasma (pigmentation particularly in the face, otherwise known as chloasma or the ‘mask of pregnancy’) (Oakley and Stanway, 2021). Linea nigra and other forms of hyperpigmentation generally appear in the first trimester and affects up to 90% of pregnant women, particularly those of colour, while melasma typically develops in the second half of pregnancy in 70% of women (Oakley and Stanway, 2021). While melasma and hyperpigmentation are not associated with adverse physical or pathological effects to either mother or baby, the psychological and psychosocial impacts of these conditions of the expectant mother can be significant. In a Brazilian descriptive study investigating physiological dermatological changes in pregnancy, 54% of the study population reported feelings of discomfort with these changes; 41.5% reported an impact on their self-esteem, and 18.7% felt that their social life had been compromised (Silva et al, 2022). However, only 14.6% received medical advice and 14.1% underwent treatment (Silva et al, 2022). This indicates the need for information on efficacious treatment modalities that do not present risk to either the pregnant woman or her developing foetus.
Ensuring safety in pregnancy: a review of the options
Because of the lack of studies and data on the treatment of pregnant women with melasma and hyperpigmentation, treatment is usually deferred until after birth, when any skin changes incurred during pregnancy may naturally disappear post-partum and when treatment risks are not as significant. However, there are some therapeutic options for those who are pregnant (Trivedi and Murase, 2023). Topical agents and chemical peels are widely used for the treatment of melasma and hyperpigmentation; however, the safety of these modalities for pregnant women requires further research, although it is generally agreed that some topical agents and chemical peels are largely suitable during pregnancy and lactation. Since 1979, the US Food and Drug Administration has assessed the safety and usability of medications in pregnancy and lactation and assigned one of five letter designations—A, B, C, D and X—in accordance with their degree of safety; while technically having been replaced by newer classification systems, this original system is still heavily referenced in the literature (Trivedi and Murase, 2023). These former categories were:
- Category A: Adequate and well-controlled studies have failed to demonstrate a risk to the foetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters);
- Category B: Animal reproduction studies have failed to demonstrate a risk to the foetus and there are no adequate and well-controlled studies in pregnant women;
- Category C: Animal reproduction studies have shown an adverse effect on the foetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drugs in pregnant women despite potential risks;
- Category D: There is positive evidence of human foetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks;
- Category X: Studies in animals or humans have demonstrated foetal abnormalities and/or there is positive evidence of human foetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits (Mospan, 2016).
» Because of the lack of studies and data on the treatment of pregnant women with melasma and hyperpigmentation, treatment is usually deferred until after birth, when any skin changes incurred during pregnancy may naturally disappear post-partum and when treatment risks are not as significant. However, there are some therapeutic options for those who are pregnant «
Topical agents
Topical agents are often used in the treatment of melasma. Historically, hydroquinone has been the gold standard, but other agents include azelaic acid, retinoid treatments, niacinamide, corticosteroid medications and salicylic and glycolic acid (Grimes et al, 2018). As can be seen in Table 1, hydroquinone and retinoids are generally not recommended for use in pregnant women, but azelaic acid and niacinamide considered to be good and safe alternatives. Azelaic acid is generally used as 20% cream twice daily for melasma, reducing the melasma area and severity index (MASI) by 50% after 8 weeks (Cassiano et al, 2022). Niacinamide is generally applied alone as 4–5% cream twice daily or in association with other lighteners; in melasma, 4% niacinamide has led to a 62% reduction of hemi-MASI after 8 weeks (Cassiano et al, 2022).
Table 1. Risk classification of commonly used dermocosmetic ingredients for the treatment of melasma according to the Food and Drug Administration (FDA)
| Agent | Action | FDA class | Restriction of use |
|---|---|---|---|
| Hydroquinone | Used with corticosteroids and retinoic acids. It can prevent the formation of melanocytes or the increase in their degradation | C | When up to 300 mg/kg is applied, it does not present toxicity in the formation of the foetus |
| Azelaic acid | It is a dicarboxylic acid and is vigorous in the treatment of melasma and post-inflammatory hyperpigmentation. It has an action to decrease tyrosinase inhibition | B | Toxicological investigations regarding fertility, teratogenicity and embryotoxicity in animals did not show any risk of use in the gestational period |
| Retinoids | Prevents keratinocyte pigmentation granules and cell turnover growth and aids in the elimination of pigment. A peeling occurs, due to the reduction of keratinisation | C | These are not indicated due to teratogenic results (central nervous system, heart, palate, ears, eyes) |
| Glycolic acid | Inhibits melanin pigment production, increases skin surface turnover, and disperses melanin already present in the surface | B |
FDA: US Food and Drug Administration.
Chemical peels
Peels use glycolic or salicylic acid-based compounds, which may increase turnover of hyperpigmented keratinocytes, but these are often secondary treatments, due to the risk of significant side effects, which include post-inflammatory hyperpigmentation (Basit et al, 2023). Glycolic acid is considered safe for those who are pregnant or breastfeeding; for the treatment of melasma, glycolic acid is usually associated with other lighteners and in creams at concentrations from 4–10% (Cassiano et al, 2022; Trivedi and Murase, 2023). There is a lack of studies conducted on the topical use of salicylic acid in pregnancy; however, a number of large studies assessing the outcomes of women who had taken low-dose acetylsalicylic acid during pregnancy reported no increase in the baseline risk of adverse events, such as major malformations, preterm birth or low birth weight, so it is likely that the relatively small doses used in topical applications will not pose serious risk to a developing foetus (Bozzo et al, 2011).
Conclusion
While not associated with morbidity or mortality, hyperpigmentation and melasma induced by pregnancy can nevertheless have a significant impact on the psychological wellbeing of the affected woman, which must be considered if a patient presents at a clinic for treatment. It is generally recommended to delay treatment until after birth but, as highlighted in this article, there are some modalities available that are considered both efficacious and safe for use during pregnancy, enabling the provision of person-centred care that facilitates the health and wellbeing of both mother and baby.
» … a number of large studies assessing the outcomes of women who had taken low-dose acetylsalicylic acid during pregnancy reported no increase in the baseline risk of adverse events, such as major malformations, preterm birth or low birth weight, so it is likely that the relatively small doses used in topical applications will not pose serious risk to a developing foetus «