Recommendation 1. Preconception counseling should be offered to all psoriasis patients of reproductive age (both men and women) (LE 2b; GR B; LA 82%).

Preconception counseling should always be offered so that patients with psoriasis can make informed decisions together with the dermatologist and also to avoid, as far as possible, unnecessary delays in conception.

Psoriasis is not a contraindication for gestation, although pregnancy can affect psoriasis; in turn, psoriasis (and its treatment) may be a risk factor for the course of the pregnancy.4,14,19–25

Preconception counseling (Table 2) ranges from information on the impact of the disease on fertility and pregnancy to the approach to an unexpected pregnancy and genetic counseling.26,27 This in turn should be adjusted to the patient’s characteristics and involve the partner where possible. Preconception counseling should be repeated periodically.

While psoriasis is not a frequently reported problem, its severity or the consequences of genital involvement (pain or embarrassment) mean that it may be associated with fertility problems.9,22,25,28–36 Some of the drugs used to treat psoriasis may also affect fertility, although this has not been demonstrated.10,37–40

Recommendation 2. The panel recommends regular assessment of the desire to become pregnant (LE 5; GR D; LA 87%).

This recommendation applies to all patients of reproductive age (both sexes), especially those who are receiving or who are candidates for long-term systemic treatment.

Recommendation 3. The panel recommends evaluating and recommending, if applicable, an effective contraceptive method panel for as long as pregnancy is not desirable (LE 2b; GR B; LA 73%).

We should recommend the use of effective contraceptive methods to both men and women, for as long as a pregnancy is not envisaged or when it is preferable to postpone it (e.g., owing to the severity of the disease, initiation of a teratogenic treatment).

Combined hormonal contraception is the most efficacious method,41 except in the case of a contraindication.42 However, the panel recommends tailoring the method to the individual case and referring the patient to a gynecologist or primary care if necessary.

While assisted reproduction is considered a gynecologic area, dermatologists who care for patients undergoing this process should be aware of the general aspects of the procedures in order to be able to provide appropriate information. The LA for the recommendation formulated with respect to this area (Recommendation 4, Table 1) was insufficient (see Discussion).

Recommendation 4. The panel recommends referring the patient to a gynecologist for reproductive counseling (LE 5; GR D; LA 46%).

Recommendation 5. Planning for pregnancy should include an assessment of the gynecologic and dermatologic history, a laboratory analysis, assessment of current psoriasis and its treatment, assessment of comorbidities, and possible contraindications to pregnancy (LE 5; GR D; LA 93%).

Recommendation 6. The panel recommends that patients be informed on an individual basis about maternal-fetal risk factors in pregnancy and about all aspects of follow-up of the pregnancy, including postpartum (LE 5; GR D; LA 81%).

Recommendation 7. The panel recommends that psoriasis is controlled as well as possible before the patient tries to become pregnant (LE 2b; GR B; LA 78%).

Pregnancy can affect psoriasis, and this (and its treatment) may be a risk factor for the course of the pregnancy.4,14,19–25 Control of psoriasis and preconception use of drugs with a low risk for the fetus make it possible to reduce the risk of maternal-fetal complications. Therefore, it is essential to plan the pregnancy and ensure collaboration with a gynecologist and primary care physician.

Planning (Tables 3 and 4) should involve a personalized preconception assessment covering the patient’s complete gynecologic and obstetric history, contraindications for pregnancy, and risk factors for maternal-fetal complications,22,25 including the drugs used before and during pregnancy (Table 5).

Psoriasis improves in 33%-60% of women during pregnancy,4,14,19 remains unchanged in 25%, and worsens in 25%.14 However, 40%-88% experience a flare-up after delivery.4,6,14,19,24,43–45

Data on the effect of psoriasis in pregnancy, childbirth, and the newborn are somewhat controversial.5,25,34,46–48 Some studies associate poor results specifically with patients who have moderate to severe psoriasis.7,48 At present, there are no data suggesting an association between psoriasis and the development of congenital malformations,7,49 and while findings are heterogeneous, there does seem to be an association between psoriasis and the development of diabetes and gestational arterial hypertension.7,48

Finally, it is also essential to ensure that psoriasis is inactive for 3-4 months, using nonteratogenic drugs. If this is not possible, then the lowest degree of activity possible should be sought on an individual basis.

Recommendation 8. The panel recommends establishing the most effective and safest pharmacological profile possible during pregnancy. This should be tailored to the individual patient (LE 5; GR D; LA 98%).

Knowledge of safety of medications is one of the pillars of effective and safe medical and obstetric care (Table 5). However, we lack sufficient evidence to provide robust, explicit recommendations for all drugs.9,50,51 Therefore, during pregnancy, drugs should be prescribed with caution, after performing a meticulous evaluation of the risks and benefits for each patient and taking informed decisions, which should be agreed with the patient.40

Recommendation 9. Potentially teratogenic topical agents (anthralin, tazarotene, topical psoralen–UV-A [PUVA]) should be discontinued once pregnancy is confirmed. Topical drugs with a more favorable safety profile should be considered (LE 3a; GR C; LA 98%).

The panel also considers it important to assess the risk-benefit ratio on an individual basis. In the case of topical drugs with a more favorable safety profile, these should be prescribed at the lowest dose possible over as small an area as possible for as short a time as possible. Occlusive dressings should be avoided (Table 5).

The only association reported for topical corticosteroids is between low birth weight and the use of high- and very-high-potency corticosteroids, especially when the duration of exposure and cumulative dose are considerable.15,52 Topical calcineurin inhibitors15 and calcipotriol have been shown to be safe. However, maternal vitamin D deficiency can be associated with a teratogenic risk. As for coal tar, there are no data to suggest teratogenicity or poor pregnancy outcome in humans, although cases of malformation have been reported in animals.15,53,54 A moderate amount of topical salicylic acid (9%-25%) can be absorbed systemically, and it has been reported that use of this agent during the first trimester could be associated with an increased risk of gastroschisis.15,55 It is important to note that phototherapy with narrowband UV-B radiation is safe during pregnancy.56

While teratogenicity and poor pregnancy outcome have not been reported with anthralin, this agent should be suspended 4 weeks before conception.15 As for topical tazarotene, it is estimated that 6% is absorbed systemically57,58; in addition, systemic absorption may increase owing to individual factors, such as damage to the skin barrier. Although there are no data pointing to embryopathy, this drug is contraindicated during pregnancy. Similarly, topical PUVA drugs are not recommended during pregnancy.15

Recommendation 10. Potentially teratogenic systemic agents (acitretin, systemic retinoids, systemic PUVA, apremilast, dimethyl fumarate, methotrexate) should be discontinued before conception. Prescription of topical and/or systemic and/or phototherapy with a better safety profile should be considered (LE 3a; GR C; LA 97%).

No cases of congenital malformations or other relevant problems have been reported for systemic corticosteroids.59–61

Acitretin is a potent teratogen in humans.62,63 It can be detected in blood 2 months after the last dose, although in some circumstances, such as the presence of alcohol, it can be converted to etretinate and be detected for 120 days. Therefore, it is usually recommended to suspend this drug for up to 2 years before conception. Cases should be managed on an individual basis.15,64,65 Other oral retinoids, such as alitretinoin and isotretinoin are also contraindicated during pregnancy.39,40

Potential associations between systemic PUVA agents and teratogenic complications remain unclear15,66,67; therefore, these agents are contraindicated during pregnancy. Narrowband UV-B phototherapy, on the other hand, has proven to be safe during pregnancy.56

No data are currently available on the teratogenic potential of apremilast in humans, although abortion and low birth weight have been reported in animals; consequently, its use is contraindicated in pregnancy.15 Similarly, the lack of data in humans for dimethyl fumarate means that this agent is not recommended.9

Animal data show that, in addition to causing abortion, methotrexate is a teratogenic drug. However, various observational studies suggest that defects are induced with doses of methotrexate greater than 10 mg/wk and that the critical period would be 6-8 weeks after conception.68–72 This drug is currently contraindicated in pregnancy and should be suspended 3 months before conception.

Finally, ciclosporin A has been associated with a greater risk of low birth weight and preterm birth in pregnant women who have received solid organ transplants, but not with a greater risk of congenital abnormalities.73–75

Recommendation 11. In the case of women receiving biologic therapy, the panel recommends that this be maintained during the first and second trimesters. Together with the patient, the clinician should evaluate the risks and benefits of continuing these drugs during the third trimester. Patients taking certolizumab pegol can continue the drug throughout pregnancy only if it is considered clinically necessary (LE 3a; GR C; LA 88%).

In the case of monoclonal antibodies, transfer of immunoglobulin (Ig) G antibodies begins in the second trimester by means of binding to placental Fc receptors.9 Nevertheless, not all monoclonal antibodies have the same affinity for binding to these receptors. IgG1 (adalimumab, infliximab, secukinumab, ustekinumab, guselkumab), IgG2 (brodalumab), and IgG4 (ixekizumab) probably cross the placenta in a similar fashion.76–78 Levels of infliximab have even been detected in newborns up to 6 months after birth. However, while etanercept has lower affinity79,80, reduced or no placental transfer has been reported mainly for certolizumab pegol (which lacks an Fc receptor).81,82

No associations have been reported for anti-TNF-α agents with respect to teratogenic capacity and poor pregnancy outcomes (including maternal infections).83,84 Data on certolizumab pegol from prospective studies with more than 500 pregnant women do not show an increased risk of malformation or miscarriage.85,86 Therefore, the regulatory agencies have approved certolizumab pegol for use during pregnancy and breastfeeding.

No or few data are available for brodalumab, ustekinumab,78,87,88 secukinumab,89 ixekizumab, and guselkumab.

Recommendation 12. Patients with psoriasis who require standard systemic treatments and/or biologics to control their disease must be followed up closely by an obstetrician once the pregnancy is confirmed (LE 5; GR D; LA 92%).

Where possible, follow-up should be in a high-risk pregnancy unit (see section on multidisciplinary care, Recommendation 15).

Recommendation 13. The panel recommends strict follow-up and monitoring of pregnant women with psoriasis (LE 5; GR D; LA 83%).

As in the case of any other patient with psoriasis, pregnant women should be evaluated in terms of their disease.

The frequency of visits depends on the obstetric assessment and the type and status of psoriasis. In general, for a clinically stable patient with low or no disease activity, visits can be every 4-6 weeks during the first 2 trimesters, increasing in frequency from week 32 onward until term, depending on the individual characteristics of the patient. In the case of flare-ups or obstetric complications, the frequency is decided by the attending physicians. Direct and fast access must be ensured for clarification of doubts and resolution of dermatologic or obstetric complications.

Evaluation should be systematic and include a basic physical examination and measurement of arterial blood pressure and weight. The laboratory analysis should include a complete blood count and simple biochemistry work-up with urinalysis (manual and sedimentation). Severity and other disease-related variables are evaluated in line with daily clinical practice.

Finally, the panel considers that the dermatologist should be involved throughout follow-up, irrespective of whether the patient has been followed in a high-risk pregnancy unit or in a general obstetrics clinic.

Recommendation 14. In the case of a flare-up, the panel recommends treating each case on an individual basis, taking into account type and severity, week of gestation, and available therapeutic options (LE 5; GR D; LA 100%).

Therapy should be decided on an individual basis in each case and agreed with the patient and, if necessary, with the gynecologist-obstetrician.

When a pregnant patient with psoriasis develops an infection requiring treatment with antibiotics, the drug chosen should have a good safety profile in pregnancy.90

Recommendation 15. The panel recommends encouraging cooperation between specialties (e.g., dermatology, obstetrics, pediatrics) (LE 5; GR D; LA 98%).

Where possible, every attempt should be made to ensure multidisciplinary care of the patient involving gynecologists experienced in high-risk pregnancies and dermatologists. This approach is greatly facilitated by the electronic medical history. Coordination with the primary care physician is also recommended.

Psoriasis itself is not a contraindication for breastfeeding, although some of the drugs prescribed to treat it may be (Table 6).91

The risk of a postpartum flare-up is important. In addition, mothers are more likely to experience Koebner phenomena owing to the irritation caused by suction and contact with the baby. Psoriasis in the area of the nipple generally manifests as well-defined erythematous plaques with fine scale.92

In principle, breastfeeding does not interfere with administration of most vaccines to the mother (both inactivated and attenuated), despite the presence of maternal antibodies in milk.93–95 An exception can be found in vaccines against smallpox and yellow fever. Since these vaccines have been associated with severe conditions in neonates, such as encephalitis, they are contraindicated.96,97

As during pregnancy, any decision taken during breastfeeding should be agreed upon with the patient.

Recommendation 16. Emollients can be prescribed during breastfeeding (LE 4; GR C, LA 83%).

There are no reports of emollients causing problems for neonates.

Recommendation 17. With respect to topical treatments for psoriasis during breastfeeding, tazarotene is contraindicated. Other topical agents can be used providing that the benefits outweigh the risks, at minimum doses, and for as short a period as possible. The area of the nipple and areola should be avoided (LE 4; GR C; LA 97%).

Despite the paucity of data, topical tazarotene is contraindicated. In general, no relevant problems have been reported for the other topical treatments, except for irritation of the baby’s skin and 1 case of iatrogenic hypertension in a baby whose mother was receiving a high-dose corticosteroid that included the area of the nipple.15,98–104

Recommendation 18. Topical PUVA is not recommended during breastfeeding. Narrowband UV-B phototherapy can be used (LE 4; GR C; LA 95%).

While there are no data on the effect on the infant,13,104 the experts recommend using another type of phototherapy. In this sense, narrowband UV-B phototherapy has proven safe during breastfeeding.56

Recommendation 19. Systemic corticosteroids can be used during breastfeeding as long as the benefits outweigh the risks. They should be administered at minimum doses and for as short a time as possible (LE 4; GR D; LA 80%).

Corticosteroids are excreted in low amounts in breast milk,105 and there have been no reports of adverse events in infants (although the studies analyzed show that the dose of corticosteroids taken by mothers was 5-10 mg/d).106

Recommendation 20. Oral retinoids, apremilast, dimethyl fumarate, methotrexate, and ciclosporin A are not recommended during breastfeeding (LE 4; GR D; LA 95%).

While oral retinoids are excreted in small amounts in breast milk, their possible cumulative toxicity remains unclear in newborns, whose immaturity may hamper their ability to eliminate these drugs.12,107

Apremilast is excreted in breast milk. While no studies have been performed in humans, the drug is contraindicated based on data from animal studies.56 Dimethyl fumarate is also excreted in breast milk, possibly at doses equivalent to the plasma doses of the mother; therefore, it is not recommended during breastfeeding.108

Methotrexate is excreted in very low concentrations in breast milk, and there are no data to suggest problems for neonates. However, since methotrexate has the capacity to accumulate in tissue, excretion could be hampered by renal immaturity in the neonate.109 Therefore, methotrexate is not recommended, as with ciclosporin A, which is also excreted, although levels in infants are almost undetectable.74,110

Recommendation 21. Certolizumab pegol has been approved for use during breastfeeding. For all other biologics, the panel recommends assessing the risks and benefits in each case (LE 4; GR D; LA 93%).

Since many monoclonal antibodies have a high molecular weight, they are excreted in breast milk in either very small amounts or not at all. Furthermore, most are digested in the newborn’s gastrointestinal tract.15,111–114 However, data on these agents are very scarce for newborns; therefore, prudence is recommended when prescribing.

Certolizumab pegol is excreted in breast milk either in very small amounts or not at all. No problems have been reported with neonates, and the drug is approved for use during breastfeeding.115

Recommendation 22. Once the pregnancy has come to term, usual follow-up should be resumed in the dermatology clinic as soon as possible (LE 5; GR D; LA 88%).

It is important to resume follow-up in the dermatology clinic as soon as possible after delivery, because there is a considerable risk of flare-ups at this time, mainly in patients whose disease was active during pregnancy, especially during the first trimester. Other factors associated with flare-ups include preterm delivery and low birth weight. The frequency of visits depends on the individual case.

Evaluation of the activity of psoriasis should be tailored in line with daily clinical practice.

Medications can be reintroduced or switched according to the patient’s progress. This means, for example, that a patient in remission whose medication was suspended because she was pregnant does not require the drug to be reintroduced while she continues to be in remission.

Recommendation 23. The neonate does not require special care, except if the mother has been exposed to biologics that cross the placenta and have been maintained beyond the second trimester (LE 5; GR D; SA 87%).

Neonates who have been exposed to drugs (monoclonal antibodies) that cross the placenta during pregnancy may have a slightly increased risk of infection over a variable period of up to 6-9 months.15 Therefore, in these cases, the newborn should be vaccinated with inactivated virus according to the vaccination schedule and with live virus only after 6 months. It is also recommended to perform laboratory testing during the first few weeks owing to the potential onset of neutropenia.