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Steroid in pregnancy       제일병원 주산기분과          전임의 안계형
Steroid의 분류• Corticosteroid- glucocorticoid: regulate many aspects of metabolism and immune function (cortisol)- mineralco...
Steroid in pregnancy• Systemic corticosteroids:  autoimmune and inflammatoryconditions• Inhaled steroids:  first-line trea...
Steroid in pregnancy    Molecular weight•   Prednisolone: 360g/mol C21H28O5•   Prednisone: 358g/mol C21H26O5•   Cortisone:...
Half life of corticosteroid
www.motherisk.org
Motherisk update 2004          Systemic corticosteroid• Prednisone, cortisone, prednisolone,  dexamethasone• Association w...
Motherisk update 2004          Systemic corticosteroid• Odd ratios (ORs) in case control studies:  threefold increase in o...
Motherisk update 2004         Systemic corticosteroid• Increase incidence of low birth weight and  stillbirths(often assoc...
Motherisk update 2004          Inhaled corticosteroids• asthma or other respiratory symptoms• beclomethasone,budesonide,fl...
Motherisk update 2004          Inhaled corticosteroidsA randomized controlled study• long-term use of low-dose budesonide ...
Motherisk update 2004          Topical corticosteroids• The systemic effects of topical corticosteroids -> generally limit...
Motherisk update 2004         Topical corticosteroids• When corticosteroids are used long term   or on large areas of skin...
Motherisk update                 discussion• oral clefts : occur at about one per thousand  births• minimal absolute effec...
Motherisk update                  discussion• When exposure has already occurred  -> a level II ultrasound scan   (to dete...
Corticosteroids During Pregnancy and Oral         Clefts: A Case-Control Study• Case subjects: 1,184 liveborn infants with...
Corticosteroids During Pregnancy and Oral       Clefts: A Case-Control Study
Corticosteroids During Pregnancy and Oral        Clefts: A Case-Control Study• Use of corticosteroids during the first  tr...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Birth Defects After Maternal Exposure to  Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological St...
Guideline on Steroids in Pregnancy  Major possible adverse effects• orofacial clefts when used preconception and in the  f...
Guideline on Steroids in PregnancyA large population-based cohort studies (84,133 pregnant women from the UK  General Prac...
Guideline on Steroids in Pregnancy• No associations of any potency with orofacial  cleft, preterm delivery, and foetal dea...
Guideline on Steroids in Pregnancy• The evidence suggests that mild/moderate  topical corticosteroids are preferred to  po...
Guideline on Steroids in Pregnancy
Guideline on Steroids in Pregnancy
Guideline on Steroids in Pregnancy
Guideline on Steroids in Pregnancy
Guideline on Steroids in Pregnancy
Guideline on Steroids in Pregnancy
Recommendations1. Mild/moderate topical corticosteroids should be   used in preference to more potent corticosteroids in  ...
Recommendations3.systemic corticosteroids have a greater  bioavailability than that of topical  corticosteroids, and have ...
Recommendations4.the danger of adverse events is increased  when areas with high absorption (e.g.genitals,  eyelids, flexu...
Recommendations6. Antibiotic-containing topical corticosteroid preparations should be avoided in pregnancy (until more rob...
Advice to women about using topical     corticosteroids in pregnancy1. Women can be reassured• no significantly increased ...
Advice to women about using topical     corticosteroids in pregnancy2. Women should be informed• small risk for foetal gro...
Williams OBSTETRICS 24th• systemic corticosteroids are category  D if used in the first trimester,  however, they are not ...
?“should be used during pregnancyonly if the potential benefit justifiesthe potential risk to the foetus”
감사합니다.
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
마더리스크라운드 - Steroid in pregnancy
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마더리스크라운드 - Steroid in pregnancy

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마더리스크라운드 - Steroid in pregnancy

  1. 1. Steroid in pregnancy 제일병원 주산기분과 전임의 안계형
  2. 2. Steroid의 분류• Corticosteroid- glucocorticoid: regulate many aspects of metabolism and immune function (cortisol)- mineralcorticoid: maintain blood volume and control renal excretion of electrolytes (aldosterone) Most medical “steroid” drugs are cortocosteroid• Anabolic steroid: interact with androgen receptors to increase muscle and bone synthesis• Sex hormone: produce sex difference or support reproduction (androgens, estrogens,progesterones)
  3. 3. Steroid in pregnancy• Systemic corticosteroids: autoimmune and inflammatoryconditions• Inhaled steroids: first-line treatment for asthma• Topical corticosteroids: allergic and inflammatory dermatologic diseases(atopic dermatitis andpsoriasis)
  4. 4. Steroid in pregnancy Molecular weight• Prednisolone: 360g/mol C21H28O5• Prednisone: 358g/mol C21H26O5• Cortisone: 376g/mol C21H28O5• Dexamethasone: 392g/mol C22H9FO5=>Cross human placenta
  5. 5. Half life of corticosteroid
  6. 6. www.motherisk.org
  7. 7. Motherisk update 2004 Systemic corticosteroid• Prednisone, cortisone, prednisolone, dexamethasone• Association with oral clefts• one case-control and several prospective cohort studies: failed to show such an association.• A metaanalysis conducted by the Motherisk program of 123175 women who received oral corticosteroids during the first trimester : showed a slightly increased risk of oral clefts.
  8. 8. Motherisk update 2004 Systemic corticosteroid• Odd ratios (ORs) in case control studies: threefold increase in oral clefts among off spring of women who received oral corticosteroids during pregnancy.• six cohort studies : no significant increase in oral clefts.
  9. 9. Motherisk update 2004 Systemic corticosteroid• Increase incidence of low birth weight and stillbirths(often associated with the condotion for which the mothers were given the drugs)
  10. 10. Motherisk update 2004 Inhaled corticosteroids• asthma or other respiratory symptoms• beclomethasone,budesonide,flunisolide,flutic asone,mometasone, and triamcinoloneIt• up to 4% of all pregnancies : complicated by maternal asthma.• Poor control of chronic asthma and exacerbation of acute asthma during pregnancy -> hypoxia, low birth weight, and intrauterine growth restriction
  11. 11. Motherisk update 2004 Inhaled corticosteroidsA randomized controlled study• long-term use of low-dose budesonide decreases the risk of severe exacerbations• improves asthma control in patients with mild, persistent asthma of recent onset.• reduce risk of hospitalization due to asthma.
  12. 12. Motherisk update 2004 Topical corticosteroids• The systemic effects of topical corticosteroids -> generally limited -> only about 3% of the medication in topical preparations is absorbed systemically following 8 hours of contact
  13. 13. Motherisk update 2004 Topical corticosteroids• When corticosteroids are used long term or on large areas of skin -> systemic effects• Epidemiologic fetal safety data on topical corticosteroids -> sparse.• Two population-based studies : treatment with topical corticosteroids during pregnancy did not increase risk of congenital abnormalities in humans.
  14. 14. Motherisk update discussion• oral clefts : occur at about one per thousand births• minimal absolute effect on the overall malformation rate of 3%.• palate formation : completed by 12 weeks’ gestation -> no risk of oral clefts exists thereafter.
  15. 15. Motherisk update discussion• When exposure has already occurred -> a level II ultrasound scan (to detect clefting)• More studies are needed to determine which cleft phenotype is associated with corticosteroids and whether it is cleft lip (with or without palate) or cleft palate alone, or both
  16. 16. Corticosteroids During Pregnancy and Oral Clefts: A Case-Control Study• Case subjects: 1,184 liveborn infants with nonsyndromic oral clefts.• results (logistic regression analysis): show a relationship between exposure to corticosteroids during the first trimester of pregnancy and an increased risk of cleft lip (with or without cleft palate) in the newborn infants (OR: 6.55; CI: 1.44–29.76; P: 0.015)
  17. 17. Corticosteroids During Pregnancy and Oral Clefts: A Case-Control Study
  18. 18. Corticosteroids During Pregnancy and Oral Clefts: A Case-Control Study• Use of corticosteroids during the first trimester of pregnancy, should be restricted to the following situations:life-threatening situationsdiseases without any other safe therapeutic alternativecases with replacement therapy.
  19. 19. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies• 184 women exposed to prednisone in pregnancy• 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure.• primary outcome: rate of major birth defects.• A meta-analysis of all epidemiological studies was conducted.
  20. 20. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies• Results: no statistical difference in the rate of major anomalies between the corticosteroid- exposed and control groups.• In the meta-analysis odds ratio for major malformations with all cohort studies:1.45 and 3.03• odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]).
  21. 21. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies• Conclusions: Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies.
  22. 22. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies
  23. 23. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies
  24. 24. Birth Defects After Maternal Exposure to Corticosteroids: Prospective Cohort Studyand Meta-Analysis of Epidemiological Studies
  25. 25. Guideline on Steroids in Pregnancy Major possible adverse effects• orofacial clefts when used preconception and in the first trimester of pregnancy, and foetal growth restriction and preterm delivery• especially potent/very potent topical corticosteroids (evidence from a Cochrane Review an d data mining of the World Health Organisation International Database of Adverse Drug Reactions)
  26. 26. Guideline on Steroids in PregnancyA large population-based cohort studies (84,133 pregnant women from the UK General Practice Research Database)• significant association of foetal growth restriction with maternal exposure to potent/very potent topical corticosteroids• but not with mild/moderate topical steroids
  27. 27. Guideline on Steroids in Pregnancy• No associations of any potency with orofacial cleft, preterm delivery, and foetal death• antibiotic-containing topical corticosteroid: associated with an increased risk for foetal growth restriction and foetal death• current evidence is sufficient for doctors and pregnant women to a well-informed decision as to whether to use topical corticosteroids in pregnancy.
  28. 28. Guideline on Steroids in Pregnancy• The evidence suggests that mild/moderate topical corticosteroids are preferred to potent/very potent ones in pregnancy, because of the risk of foetal growth restriction.
  29. 29. Guideline on Steroids in Pregnancy
  30. 30. Guideline on Steroids in Pregnancy
  31. 31. Guideline on Steroids in Pregnancy
  32. 32. Guideline on Steroids in Pregnancy
  33. 33. Guideline on Steroids in Pregnancy
  34. 34. Guideline on Steroids in Pregnancy
  35. 35. Recommendations1. Mild/moderate topical corticosteroids should be used in preference to more potent corticosteroids in pregnancy (Grade of recommendation: B).2.Potent/very potent topical corticosteroids should be used as second-line therapy for as short a time as possible, and appropriate obstetric care should be provided as they increase the risk of foetal growth restriction (Grade of recommendation: B).
  36. 36. Recommendations3.systemic corticosteroids have a greater bioavailability than that of topical corticosteroids, and have a higher potential for foetotoxicity than topical corticosteroids (systemic corticosteroids are associated with a reduction in fetal birth weight and an increase in preterm delivery and should not be used in preference (Grade of recommendation: B).
  37. 37. Recommendations4.the danger of adverse events is increased when areas with high absorption (e.g.genitals, eyelids, flexures) are treated (Grade of recommendation: B)5.The data are not available to determine if newer more lipophilic topical corticosteroids (mometasone, fluticasone and methylprednisolone aceponate,) with a good therapeutic index are associated with less foetal growth restriction despite theoretical grounds to suggest this and the practical advantage of once daily application (Grade of recommendation:C).
  38. 38. Recommendations6. Antibiotic-containing topical corticosteroid preparations should be avoided in pregnancy (until more robust evidence is available) because of concern for increased risk for foetal growth restriction and foetal death. (Grade of recommendation: C).
  39. 39. Advice to women about using topical corticosteroids in pregnancy1. Women can be reassured• no significantly increased risk for orofacial cleft, preterm delivery and foetal death when using topical corticosteroids in pregnancy.• no increased risk for foetal growth restriction when using mild/moderate topical corticosteroids in pregnancy.
  40. 40. Advice to women about using topical corticosteroids in pregnancy2. Women should be informed• small risk for foetal growth restriction when using potent/very potent topical corticosteroids• but this risk is less than that of systemic corticosteroids• additional risk for preterm delivery has been found in women using systemic corticosteroids.3. Depending on the severity of their skin conditions, women should use topical corticosteroids of the least potency required and limit the amount of use
  41. 41. Williams OBSTETRICS 24th• systemic corticosteroids are category D if used in the first trimester, however, they are not considered to represent a major teratogenic risk.
  42. 42. ?“should be used during pregnancyonly if the potential benefit justifiesthe potential risk to the foetus”
  43. 43. 감사합니다.

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