About Authors:
Patel Brilina M*, Yadav Nisha D, Maheta Payal, Arora Bhoomi
Institute of clinical research India,
Ahmedabad,
Gujarat, India
*patelbrilina@gmail.com
Abstract:
Corticosteroids, often referred to as steroid medications, contain man-made versions of the hormone cortisol. Corticosteroids are mainly used to relieve inflammation. Inflammation occurs when the immune system causes part of the body to become swollen, red and filled with fluid in response to an infection. The immune system is the body’s natural defence against infection and illness. Steroids form an important component in pregnancy to reduce the inflammation and are used since very long time for different conditions in different forms. Though very few molecules are used since very long time. Now increase knowledge in uses of corticosteroids in pregnant women who suffer from asthma, skin diseases, rheumatoid arthritis etc.
Reference Id: PHARMATUTOR-ART-1350
Introduction:
Corticosteroids refer to a group of hormones made within the adrenal cortex. Since these hormones play a critical role in maintaining carbohydrate reserves, they are often referred to as glucocorticoids. The excess or deficiency of these hormones affects virtually every tissue in the body. It is tightly regulated by the central nervous system, which is very sensitive to negative feedback by the circulating cortisol and exogenous (synthetic) corticosteroids[1]. About fifty years ago corticosteroids were synthesized for their anti-inflammatory and immuno -suppressive properties[2] so it has a wide range of clinical uses. Corticosteroids are generally safe to use in pregnancyto reduce the immune response in allergic or inflammatory diseases, such as asthma, lupus, rheumatoid arthritis, or skin diseases. Other indications include: promoting fetal lung maturity, treating infertility and maintaining pregnancy, or as replacement hormone therapy[3]. Corticosteroids are available alone or in combination with other drugs for systemic, inhaled, and topical use. Systemic corticosteroids are used for autoimmune and inflammatory conditions. Inhaled steroids are now first-line treatment for asthma. Topical corticosteroids are frequently used to treat allergic and inflammatory dermatologic diseases, such as atopic dermatitis and psoriasis. Now we will focus on recent progress in our understanding of use of corticosteroids in pregnant women who are suffering from asthma, lupus, rheumatoid arthritis, or skin diseases etc.
The primary mechanism of action of corticosteroids is at the cellular level. These drugs appear to bind to intracellular receptors, alter gene expression and ultimately regulate cellular processes[4,5]. Their anti-inflammatory effect results from several different factors including inhibition of phospholipase, alterations in lymphocytes, inhibition of cytokine expression and stabilization of the cellular membrane [6]. Corticosteroids inhibit the action of phospholipase and thus prevent the formation of arachidonic acid and subsequently the inflammatory mediators.
Use of corticosteroids in different diseases in pregnancy:
Asthma may be the most common potentially serious medical condition to complicate pregnancy[7]. Asthma is a chronic inflammatory disease of the airways that is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli[8]. Asthma-related morbidity and mortality rates in pregnant women are comparable to those in the general population. The mortality rate from asthma in the United States is 2.1 persons per 100,000[9]. Poor control of chronic asthma and exacerbation of acute asthma during pregnancy can result in adverse maternal and fetal outcomes, such as hypoxia, low birth weight, and intrauterine growth restriction[10,11].Inhaled corticosteroids used to treat asthma include beclomethasone, budesonide, flunisolide, fluticasone, mometasone, and triamcinolone [12]. These drugshelp to control the swelling of the airways in the lungs and reduce mucus production so that asthma attacks are less likely. Inhaled corticosteroids improve the symptoms and are helpful in the management of asthma and thus can be used comfortably during pregnancy[13]. Commonly used systemic corticosteroids include prednisone, cortisone, and the active metabolites of prednisone and dexamethasone. Corticosteroids cross human placenta [14].The increased incidence of low birth weight and stillbirths reported in fetuses exposed to corticosteroids can often be linked to the conditions for which the mothers were given the drugs[15].Prednisone during pregnancy has been associated with cleft lip or palate, premature delivery, and low birth weight[16]. Rodríguez-Pinilla E, Martínez-Frías MLdone the study of 1184 cases of cleft lip suggested a possible association with oral corticosteroid treatment[17].Of the five affected pregnancies in the latter study, two were complicated by multiple congenital abnormalities and in another case the mother was taking only replacement steroids for Addison's disease. Thus, only two pregnancies (no more than control) were complicated by isolated cleft lip in women taking therapeutic doses of corticosteroids. A larger case-control study of 20,830 cases of congenital abnormality revealed no association between the rate of different congenital abnormalities and corticosteroid treatment in the second and third months of gestation[18]. An increased risk of pregnancy induced hypertension and pre-eclampsia has been reported in asthmatic women treated with oral corticosteroids[19,20,21].Inhaled corticosteroids are currently recommended as part of routine management of moderate-to-severe chronic asthma during pregnancy[22].
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Lupus: Systemic lupus erythematosus (SLE) occurs frequently in women of childbearing age. Although patients with SLE are as fertile as women in the general population, their pregnancies may be associated with complications[23]. One study prospectively evaluated 40 pregnancies in 37 women with SLE[23]. Flare occurred in 24 (60%) of the pregnancies. Comparison of the rates of flare in the same patients after delivery and in nonpregnant patients with SLE showed a significant increase in the rate of flare during pregnancy. Flares presented most commonly as constitutional symptoms, renal disease, or involvement of the skin and joints. Similar findings were found in another prospective study of 68 patients with SLE[23]. The multicentre study done by Hayslett et al involved 65 pregnancies from 47 patients with history of lupus nephritis, it was described that of the 25 pregnancies with active renal disease at conception, 48% had flares of nephritis[24]. This percentage was higher than that of pregnancies with inactive renal disease at the time of conception (32%). Jungers et al reported that 12 of 26 (46%) lupus pregnancies had the flare as a prime symptom[25]. chronic hypertension occurs in 28% of pregnant women with lupus, hypertensive complications are similarly increased in mothers with and without a history of pre-pregnancy hypertension[26]. The frequencies of spontaneous abortions and stillbirths are increased in women with lupus, with the stillbirth rate nearly 5 times greater than that for non-lupus pregnancies[27].
Corticosteroids are relatively safe to use during pregnancy from a fetal standpoint, but they may contribute to maternal hypertension and gestational diabetes. It acts by decreasing inflammation and exerts effect through genomic mechanisms by binding to DNA[28]. Prednisone, prednisolone, and methylprednisolone have minimal placental transfer and are the drugs of choice during pregnancy. Fluorinated corticosteroids such as dexamethasone and betamethasone easily cross the placenta and should not be used unless there is intent to treat the fetus. So far, no major adverse effects of corticosteroids on babies have been reported in various published series of lupus pregnancies[29,30,31].
Long term use of corticosteroids has adverse effect such as fetal adrenal suppression, congenital cataracts, fetal immunosuppression, neonatal Congenital cytomegalovirus (CVM) infection, preterm delivery if dose is more than 20 mg during late pregnancy, maternal hypertension and gestational diabetes. But may continue during pregnancy with lupus[28]. It was reported that the use of high dose corticosteroids during pregnancy is associated with premature rupture of the membranes, Intrauterine growth retardation(IUGR) and precipitation of maternal complications such as gestational diabetes, hypertension, osteoporosis, and avascular bone necrosis[32].
Corticosteroids are also used in other skin diseases in pregnancy for example; eczema, psoriasis, etc. The hydrocortisone/cortisone is an inactive precursor, cortisone has half-life of 8-12 hours[33], and is reduced by the liver to hydrocortisone. It is most typically used topically to treat eczema or other related skin diseases, and has also been found effective in treating hyperemesis gravidarum. Mild or moderate topical corticosteroids combined with moisturizer-based emollients are the first line of treatment for mild to moderate eczema during pregnancy[34]. Systemic steroids are generally avoided since they can cause recurrence of flares when discontinued and may have side effects on early embryo development. Systemic treatment is also not generally regarded as safe for lactating mothers as the corticosteroids crosses placenta and appears in the milk[34]. The combination of betamethasone and salicyclic acid is used to treat dry, scaly, inflammatory skin disorders such as eczema and psoriasis[35].
Rheumatoid arthritis (RA): In many women with RA, disease activity improves substantially during pregnancy. However, some women faced problem of flares and it remains active during pregnancy. Thus, it is often necessary to change or modify treatment of RA during pregnancy to control flares while minimizing the risks of RA treatments to the developing foetus. Many changes to the immune system occur normally during pregnancy. These changes enable a fetus to grow and develop. Some of these changes contribute to the improvement of RA symptoms during pregnancy. In 2008, De Man et al reported that disease activity decreased during pregnancy but increased after delivery[36]. The investigators monitored 84 patients with RA for disease activity before conception; at each trimester of pregnancy, if possible; and at 6, 12, and 26 weeks postpartum. Among patients with at least moderate disease activity in the first trimester, 48% had a moderate response during pregnancy, whereas patients with low disease activity in the first trimester reported that their disease activity remained stable during pregnancy[36].Thirty-nine percent of patients had at least 1 moderate flare postpartum.
The most commonly used short-acting steroids are prednisone, prednisolone and methylprednisolone, and fluorinated slow acting steroids such as dexamethasone and betamethasone. If dexamethasone and betamethasone are used in pregnant women to treat RA, the high concentration of these drugs found in fetus. While prednisone, prednisolone and methylprednisolone cross the placental barrier but do not reach large concentrations in the fetus[37]. Cortisone injections can also be used in pregnancy without problems. In utero exposure to fluorinated corticosteroids should be considered when evaluating postnatal steroid therapy[38]. The use of corticosteroids has been associated in children with cleft palate (if used in the first quarter and especially at doses higher than 15 mg/kg body weight per day), premature rupture of membranes, intrauterine growth retardation and preterm birth while in the mother they cause hypertension, gestational diabetes, infection, and osteoporosis[38,39].
Dexamethasone is a glucocorticoid and it is most commonly used in the third trimester to reduce fetal respiratory distress. It is available in the form of topical preparations. It is also used in the first trimester to treat the virilization associated with congenital adrenal hyperplasia, since it suppresses adrenal function. The safety and effectiveness of dexamethasone therapy is debatable but most authors agree that this treatment has been effective in some populations[40]. More importantly, this drug exposure is not associated with long term adverse effects in the offspring[41]. The long-term effects of dexamethasone therapy in babies may include increased fetal death, growth retardation, adult hypertension, and psychological effects[40]. Due to its longer half life of 36 –54 hours [42], dexamethasone is generally not suggested for treatment of maternal disease.
Betamethasone is a synthetic corticosteroid used to promote fetal lung maturation in the third trimester, and is also found in some topical preparations.
Two new studies reported mixed signals about the long-term safety of repeatedly given steroids in pregnant women to prevent complications, once a premature delivery seems likely.
The first study, led by Caroline Crowther of the University of Adelaide in Australia, found that 84% of the 521 fetuses exposed to more than one steroid treatment were free of a major disability at the age of 2. This compared to 81% of the 526 children from mothers who had been given placebo shots after the first steroid injection. The second study, concentrated the children with the age of 2 to 3 years, found that infant development scores were the same for 235 children who has been exposed to betamethasone and 230 whose mothers had been given placebo shots. However the team, led by Ronald Wapner of Columbia University in New York, found that 2.9 % of the steroid-treated pregnancies produced a baby with cerebral palsy, compared to a rate of 0.5 % among the children of placebo recipients.
The studies found that the mothers who received extra injections of the steroid betamethasone delivered babies that were not any different from normal in their body size measurements and had no significant differences in blood pressure or development at age 2 or 3.
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Conclusion:
Overall topical corticosteroids appear to be safe during pregnancy. High-potency topical corticosteroids should be avoided if possible and when they must be used they should be used only for the shortest period possible. Use of corticosteroids did not seem to increase the risk of congenital malformations, but the estimates are imprecise. Use of inhaled corticosteroids was associated with a slightly increased risk of miscarriage. For maternal disease, derivatives of cortisone and prednisone are suggested since they are more readily inactivated by the placenta, as opposed to dexamethasone and betamethasone, which are more likely to reach the fetus in the active state.
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